Recombinant Wingless-Type MMTV Integration Site Family, Member 1 (WNT1) 蛋白. 宿主: 人. 宿主: 大肠杆菌（E. Coli）. 产品编号 ABIN413893.

Wingless-Type MMTV Integration Site Family, Member 6 (WNT6) Peptide. Species: Human. Source: Synthetic. Order product ABIN2185204.

Wingless-Type MMTV Integration Site Family, Member 8B (WNT8B) Peptide. Species: Human. Source: Synthetic. Order product ABIN1540886.

K06765 DCC; deleted in colorectal carcinoma K02187 CASP3; caspase 3 [EC:3.4.22.56] K04399 CASP9; caspase 9 [EC:3.4.22.62] K08733 APPL1; DCC-interacting protein 13 alpha K05689 CDH1; cadherin 1, type 1, E-cadherin K02105 CTNNB1; catenin beta 1 K05691 CTNNA; catenin alpha K05691 CTNNA; catenin alpha K05691 CTNNA; catenin alpha K02157 AXIN1; axin 1 K04385 AXIN2; axin 2 K02085 APC; adenomatosis polyposis coli protein K02085 APC; adenomatosis polyposis coli protein K03083 GSK3B; glycogen synthase kinase 3 beta [EC:2.7.11.26] K02620 TCF7; transcription factor 7 K04490 TCF7L1; transcription factor 7-like 1 K04491 TCF7L2; transcription factor 7-like 2 K04492 LEF1; lymphoid enhancer-binding factor 1 K08731 BIRC5; baculoviral IAP repeat-containing protein 5 K04377 MYC; Myc proto-oncogene protein K03209 WNT1; wingless-type MMTV integration site family, member 1 K00182 WNT2; wingless-type MMTV integration site family, member 2 K00182 WNT2; wingless-type MMTV integration site family, member 2 K00312 WNT3; ...

K06765 DCC; deleted in colorectal carcinoma K02187 CASP3; caspase 3 [EC:3.4.22.56] K04399 CASP9; caspase 9 [EC:3.4.22.62] K08733 APPL1; DCC-interacting protein 13 alpha K05689 CDH1; cadherin 1, type 1, E-cadherin K02105 CTNNB1; catenin beta 1 K05691 CTNNA; catenin alpha K05691 CTNNA; catenin alpha K05691 CTNNA; catenin alpha K02157 AXIN1; axin 1 K04385 AXIN2; axin 2 K02085 APC; adenomatosis polyposis coli protein K02085 APC; adenomatosis polyposis coli protein K03083 GSK3B; glycogen synthase kinase 3 beta [EC:2.7.11.26] K02620 TCF7; transcription factor 7 K04490 TCF7L1; transcription factor 7-like 1 K04491 TCF7L2; transcription factor 7-like 2 K04492 LEF1; lymphoid enhancer-binding factor 1 K08731 BIRC5; baculoviral IAP repeat-containing protein 5 K04377 MYC; Myc proto-oncogene protein K04503 CCND1; G1/S-specific cyclin-D1 K03209 WNT1; wingless-type MMTV integration site family, member 1 K00182 WNT2; wingless-type MMTV integration site family, member 2 K00182 WNT2; wingless-type MMTV integration ...

An increasing number of studies address the roles of Wnt proteins in shaping leukocyte functions. Recombinant Wnt3a and Wnt5a, prototypical activators of β-Catenin-dependent and -independent Wnt signaling, respectively, are widely used to investigate the effects of Wnt proteins on myeloid cell functions. Recent reports describe both proinflammatory and immunemodulatory effects of Wnt3a and Wnt5a on macrophages, DCs, and microglia. The underlying molecular mechanisms for this divergence are unclear. We show here that recombinant Wnt3a- and Wnt5a-induced cytokine production from murine C57BL/6 macrophages was dependent on TLR4 and inhibited by Polymyxin B. Similarly, impairment of TLR-induced cytokine production upon preexposure to Wnt proteins was TLR4 dependent. The extent of Wnt3a- and Wnt5a-induced inflammatory gene expression greatly varied between Wnt protein lots. We conclude that cytokine responses and TLR tolerization induced by recombinant Wnt proteins are likely explained by ...

Wingless-Type MMTV Integration Site Family, Member 3A Human Recombinant, Protein Wnt-3a, MGC119418, MGC119419, MGC119420, WNT3A, wingless-type MMTV integration site family member 3A.

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MENEZES, Marina de Pádua Nogueira et al. Canonical and noncanonical Wnt pathways: a comparison between endometrial cancer type I and atrophic endometrium in Brazil. Sao Paulo Med. J. [online]. 2011, vol.129, n.5, pp.320-324. ISSN 1516-3180. http://dx.doi.org/10.1590/S1516-31802011000500007.. CONTEXT AND OBJECTIVE: The Wnt pathway is involved in tumorigenesis of several tissues. For this reason, we proposed to evaluate Wnt gene expression in endometrial cancer type I. DESIGN AND SETTING: Cross-sectional study on materials gathered from the tissue bank of the Department of Pathology, Universidade Federal de São Paulo. METHODS: Endometrial specimens were obtained from surgeries performed between 1995 and 2005 at São Paulo Hospital, Universidade Federal de São Paulo. The material was divided into two groups according to tissue type: Group A, atrophic endometrium (n = 15); and Group B, endometrial adenocarcinoma (n = 45). We compared the immunohistochemical expression of Wnt1, Frizzled-1 (FZD1), ...

Recent genetic studies in Drosophila identified a novel non-canonical Wnt pathway, the planar cell polarity (PCP) pathway, that signals via JNK to control epithelial cell polarity in Drosophila. Most recently, a pathway regulating convergent extension movements during gastrulation in vertebrate embryos has been shown to be a vertebrate equivalent of the PCP pathway. However, it is not known whether the JNK pathway functions in this non-canonical Wnt pathway to regulate convergent extension movements in vertebrates. In addition, it is not known whether JNK is in fact activated by Wnt stimulation. Here we show that Wnt5a is capable of activating JNK in cultured cells, and present evidence that the JNK pathway mediates the action of Wnt5a to regulate convergent extension movements in Xenopus. Our results thus demonstrate that the non-canonical Wnt/JNK pathway is conserved in both vertebrate and invertebrate and define that JNK has an activity to regulate morphogenetic cell movements ...

Acting as intercellular signals, Wnt proteins regulate the proliferation of cells. Wnt signals are active in numerous contexts, initially in early development and later during the growth and maintenance of various tissues. In comparison to other growth factors, Wnt signals have several unique properties, including a short range of action. Thereby, Wnts predominantly mediate signaling locally, between neighboring cells. In addition, Wnt signals give shape to tissues as cells are proliferating. This is a consequence of the ability of Wnt signaling to confer polarity and asymmetry to cells. Wnt proteins are highly conserved in evolution and are active in every branch of the animal kingdom.. Wnt signaling is often implicated in stem cell control, as a proliferative and self-renewal signal. Mutations in Wnt genes or Wnt pathway components lead to specific developmental defects, while various human diseases, including cancer, are caused by abnormal Wnt signaling. Insights into the mechanisms of Wnt ...

Wingless-type MMTV integration site family member 2 (WNT2) has a potentially important role in neuronal development; however, there has yet to be an investigation into the association between single nucleotide polymorphisms (SNPs) of WNT2 and schizophrenia. This study aimed to determine whether certain SNPs of WNT2 were associated with schizophrenia in a Korean population. e genotyped 7 selected SNPs in the WNT2 gene region (approximately 46 Kb) using direct sequencing in 288 patients with schizophrenia and 305 healthy controls. Of the SNPs examined, one SNP showed a weak association with schizophrenia (p = 0.017 in the recessive model). However, this association did not remain statistically significant after Bonferroni correction. The present study does not support a major role for WNT2 in schizophrenia. This could be due to the size of the population. Therefore, additional studies would be needed to definitively rule out the genes minor effects.

The Wnt signaling pathways are a group of signal transduction pathways made of proteins that pass signals from outside of a cell through cell surface receptors to the inside of the cell. Three Wnt signaling pathways have been characterized: the canonical Wnt pathway, the noncanonical planar cell polarity pathway, and the noncanonical Wnt/calcium pathway. All three Wnt signaling pathways are activated by the binding of a Wnt-protein ligand to a Frizzled family receptor, which passes the biological signal to the protein Dishevelled inside the cell. The canonical Wnt pathway leads to regulation of gene transcription, the noncanonical planar cell polarity pathway regulates the cytoskeleton that is responsible for the shape of the cell, and the noncanonical Wnt/calcium pathway regulates calcium inside the cell. The clinical importance of Wnt signaling pathway has been demonstrated by mutations that lead to a variety of diseases, including breast and prostate cancer, glioblastoma, type II ...

The Wnt signaling pathways are a group of signal transduction pathways made of proteins that pass signals into a cell through cell surface receptors. Three Wnt signaling pathways have been characterized: the canonical Wnt pathway, the noncanonical planar cell polarity pathway, and the noncanonical Wnt/calcium pathway. All three pathways are activated by binding a Wnt-protein ligand to a Frizzled family receptor, which passes the biological signal to the Dishevelled protein inside the cell. The canonical Wnt pathway leads to regulation of gene transcription, and is thought to be negatively regulated in part by the SPATS1 gene. The noncanonical planar cell polarity pathway regulates the cytoskeleton that is responsible for the shape of the cell. The noncanonical Wnt/calcium pathway regulates calcium inside the cell. Wnt signaling pathways use either nearby cell-cell communication (paracrine) or same-cell communication (autocrine). They are highly evolutionarily conserved in animals, which means ...

The Wnt signal transduction pathway is important in a wide variety of developmental processes as well as in the genesis of human cancer. Vertebrate Wnt pathways can be functionally separated into two classes, the canonical Wnt/beta-catenin pathway and the non-canonical Wnt/Ca2+ pathway. Supporting differences in Wnt signaling, gain of function of Wnt-1 in C57mg mouse mammary epithelial cells leads to their morphological transformation while loss of function of Wnt-5a leads to the same transformation. Many downstream target genes of the Wnt/beta-catenin pathway have been identified. In contrast, little is known about the Wnt/Ca2+ pathway and whether it regulates gene expression. To test the hypothesis that a specific cell line can respond to distinct Wnts with different patterns of gene expression, we over-expressed Wnt-5a and Rfz-2 in C57mg mammary epithelial cells and compared this cell line to C57mg cells over-expressing Wnt-1. These Wnts were chosen since previous studies suggest that C57mg cells

During Xenopus laevis gastrulation, convergent extension is required for the mesoderm to extend into the embryo and shape the embryonic body plan. Recent results from our lab suggest that the inhibition of aquaporin3b (aqp3b) prevents convergent extension of the mesoderm and that aqp3b acts through noncanonical Wnt signaling. Wnt signaling is a key signaling pathway for embryo and tissue development. There are two types of Wnt signaling pathways, the canonical and the noncanonical pathways. There are three separate branches to noncanonical Wnt signaling. Our lab has shown that aqp3b acts through the noncanonical Wnt/Ca2+ pathway and that it acts upstream of the cytoplasmic Wnt signaling pathway member Disheveled (Dsh). The Frizzled7 (fzd7) membrane receptor is part of the noncanonical Wnt/Ca2+ pathway and also acts upstream of Disheveled (Dsh). I will test, whether in this signaling cascade, aqp3b acts upstream or downstream of fzd7. Thus, I will test whether fzd7 activates aqp3b, if aqp3b ...

WNT7A - WNT7A (Myc-DDK-tagged)-Human wingless-type MMTV integration site family, member 7A (WNT7A) available for purchase from OriGene - Your Gene Company.

WNT1 - WNT1 (GFP-tagged) - Human wingless-type MMTV integration site family, member 1 (WNT1) available for purchase from OriGene - Your Gene Company.

Wnt signals exercise strong cell-biological and regenerative effects of considerable therapeutic value. There are, however, no specific Wnt agonists and no method for in vivo delivery of purified Wnt proteins. Wnts contain lipid adducts that are required for activity and we exploited this lipophilicity by packaging purified Wnt3a protein into lipid vesicles. Rather than being encapsulated, Wnts are tethered to the liposomal surface, where they enhance and sustain Wnt signaling in vitro. Molecules that effectively antagonize soluble Wnt3a protein but are ineffective against the Wnt3a signal presented by a cell in a paracrine or autocrine manner are also unable to block liposomal Wnt3a activity, suggesting that liposomal packaging mimics the biological state of active Wnts. When delivered subcutaneously, Wnt3a liposomes induce hair follicle neogenesis, demonstrating their robust biological activity in a regenerative context ...

Intestinal intraepithelial lymphocytes that reside within the epithelium of the intestine form one of the main branches of the immune system. A majority of IELs express CD8α homodimer together with other molecules associated with immune regulation. Growing evidence points to the WNT signaling pathway as a pivotal piece in the immune balance and focuses on its direct regulation in intestinal epithelium. Therefore we decided to investigate its role in IELs immune status determination. DSS colitis was induced in male C57BL mice. IELs were isolated from colon samples using mechanical dissociation followed by percoll gradient purification and Magnetic-activated cell sorting. Phenotype and cytokine production and condition with Wnts were analyzed by flow cytometry, real-time PCR or ELISA. Proliferation of lymphocytes were evaluated using CFSE dilution. Cell responses after WNT pathway interference were also evaluated. Non-canonical WNT pathway elements represented by FZD5, WNT5A and NFATc1 were remarkably

Author(s): Aznar, Nicolas; Sun, Nina; Dunkel, Ying; Ear, Jason; Buschman, Matthew D; Ghosh, Pradipta | Abstract: Cellular proliferation is antagonistically regulated by canonical and noncanonical Wnt signals; their dysbalance triggers cancers. We previously showed that a multimodular signal transducer, Daple, enhances PI3-K→Akt signals within the noncanonical Wnt signaling pathway and antagonistically inhibits canonical Wnt responses. Here we demonstrate that the PI3-K→Akt pathway serves as a positive feedback loop that further enhances noncanonical Wnt signals by compartmentalizing β-catenin. By phosphorylating the phosphoinositide- (PI) binding domain of Daple, Akt abolishes Daples ability to bind PI3-P-enriched endosomes that engage dynein motor complex for long-distance trafficking of β-catenin/E-cadherin complexes to pericentriolar recycling endosomes (PCREs). Phosphorylation compartmentalizes Daple/β-catenin/E-cadherin complexes to cell-cell contact sites, enhances noncanonical Wnt signals

Wnt proteins are secreted morphogens that are required for basic developmental processes, such as cell-fate specification, progenitor-cell proliferation and the control of asymmetric cell division, in many different species and organs. There are at least three different Wnt pathways: the canonical pathway, the planar cell polarity (PCP) pathway and the Wnt/Ca2+ pathway. In the canonical Wnt pathway, the major effect of Wnt ligand binding to its receptor is the stabilization of cytoplasmic beta-catenin through inhibition of the bea-catenin degradation complex. Beta-catenin is then free to enter the nucleus and activate Wnt-regulated genes through its interaction with TCF (T-cell factor) family transcription factors and concomitant recruitment of coactivators. Planar cell polarity (PCP) signaling leads to the activation of the small GTPases RHOA (RAS homologue gene-family member A) and RAC1, which activate the stress kinase JNK (Jun N-terminal kinase) and ROCK (RHO-associated ...

Wnt proteins are secreted morphogens that are required for basic developmental processes, such as cell-fate specification, progenitor-cell proliferation and the control of asymmetric cell division, in many different species and organs. There are at least three different Wnt pathways: the canonical pathway, the planar cell polarity (PCP) pathway and the Wnt/Ca2+ pathway. In the canonical Wnt pathway, the major effect of Wnt ligand binding to its receptor is the stabilization of cytoplasmic beta-catenin through inhibition of the bea-catenin degradation complex. Beta-catenin is then free to enter the nucleus and activate Wnt-regulated genes through its interaction with TCF (T-cell factor) family transcription factors and concomitant recruitment of coactivators. Planar cell polarity (PCP) signaling leads to the activation of the small GTPases RHOA (RAS homologue gene-family member A) and RAC1, which activate the stress kinase JNK (Jun N-terminal kinase) and ROCK (RHO-associated ...

The member 3a of Wingless-type MMTV integration site family (Wnt3a) as an oncogene is overexpressed in many kinds of tumors with a worse outcome. However, the mechanism and alteration of Wnt3a...

WNT signaling is crucial for tissue morphogenesis during development in all multicellular animals. After birth, WNT/CTNNB1 responsive stem cells are responsible for tissue homeostasis in various organs and hyperactive WNT/CTNNB1 signaling is observed in many different human cancers. The first link between WNT signaling and breast cancer was established almost 40 years ago, when Wnt1 was identified as a proto-oncogene capable of driving mammary tumor formation in mice. Since that discovery, there has been a dedicated search for aberrant WNT signaling in human breast cancer. However, much debate and controversy persist regarding the importance of WNT signaling for the initiation, progression or maintenance of different breast cancer subtypes. As the first drugs designed to block functional WNT signaling have entered clinical trials, many questions about the role of aberrant WNT signaling in human breast cancer remain. Here, we discuss three major research gaps in this area. First, we still lack a basic

Wnt signal transduction pathway (Wnt STP) is a crucial intracellular pathway mainly due to its participation in important biological processes, functions, and diseases, i.e., embryonic development, stem-cell management, and human cancers among others. This is why Wnt STP is one of the highest researched signal transduction pathways. Study and analysis of its origin, expansion and gradual development to the present state as found in humans is one aspect of Wnt research. The pattern of development and evolution of the Wnt STP among various species is not clear till date. A phylogenetic tree created from Wnt STPs of multiple species may address this issue. In this respect, we construct a phylogenetic tree from modules of Wnt STPs of diverse species. We term it as the Module Tree. A module is nothing but a self-sufficient minimally-dependent subset of the original Wnt STP. Authenticity of the module tree is tested by comparing it with the two reference trees. The module tree performs better than an

Frizzled proteins are seven-transmembrane proteins that act as the primary receptors for Wnt signals. Wnts can bind the the CRD (cysteine-rich domain) of Frizzled. The structure of Wnt as bound to its receptor Frizzled shows that the lipid, sticking out of the Wnt protein, inserts into a hydrophobic cavity in Frizzled (Janda et al, 2012).. LRPs and Arrow in Drosophila are long single-pass transmembrane proteins. Arrow is genetically required for Wingless signaling (Wehrli, 2000) and mouse LRP mutations are similar in phenotype to Wnt mutants (Pinson, 2000).. Beyond the well known receptors Frizzled and LRP, there are several other transmembrane proteins that act as specific receptors for Wnt proteins or the Wnt agonists, such as R-Spondin. In several cases, these receptors play a role in alternative Wnt pathways. See MacDonald and He (2012), Niehrs (2012) and van Amerongen et al (2008) for reviews. R-spondins interact on the cell surface with members of the LGR5 family, to enhance Wnt signaling ...

Clone REA603 recognizes the mouse frizzled-1 antigen. Frizzled-1 is a member of the frizzled family of proteins which encode seven-transmembrane domain proteins that are receptors for the wingless-type MMTV integration site family of signaling proteins. Frizzled-1 is expressed primarily in the developing lung mesenchyme, in adult heart, placenta, kidney, pancreas, prostate, and ovary. Frizzled-1 interacts with Wnt7b.Additional information: Clone REA603 displays negligible binding to Fc receptors. | Ireland

Canonical Wnt signaling triggering β-catenin-dependent gene expression contributes to cell cycle progression, in particular at the G1/S transition. Recently, however, it became clear that the cell cycle can also feed back on Wnt signaling at the G2/M transition. This is illustrated by the fact that mitosis-specific cyclin-dependent kinases can phosphorylate the Wnt co-receptor LRP6 to prime the pathway for incoming Wnt signals when cells enter mitosis. In addition, there is accumulating evidence that various Wnt pathway components might exert additional, Wnt-independent functions that are important for proper regulation of mitosis. The importance of Wnt pathways during mitosis was most recently enforced by the discovery of Wnt signaling contributing to the stabilization of proteins other than β-catenin, specifically at G2/M and during mitosis. This Wnt-mediated stabilization of proteins, now referred to as Wnt/STOP, might on one hand contribute to maintaining a critical cell size required for ...

Members of the Wnt family of secreted signalling proteins play many crucial roles during embryonic development. Wnt signalling is negatively regulated by secreted Frizzled-related proteins (sFRPs), which bind to Wnts extracellularly, but now, on p. 4083, Yusuke Mii and Masanori Taira report that the sFRPs Frzb and Crescent (Cres) can expand the signalling range of Wnts by enhancing their diffusion. By microinjecting mRNAs for tagged versions of Wnt8, Wnt11, Frzb or Cres into Xenopus embryos, the researchers show that Wnts do not diffuse effectively, whereas sFRPs spread widely. However, they report, the expression of an sFRP and a tagged Wnt in the same blastomere or in separate oocytes that are then co-cultured promotes Wnt diffusion. Most importantly, Wnt8 conveyed by sFRPs activates Wnt signalling at a distance from its source in vitro and in vivo, even though sFRPs usually act as Wnt inhibitors. Overall, these results provide new insights into how the range of Wnt signalling is regulated in ...

Dopamine-synthesizing (dopaminergic, DA) neurons in the ventral midbrain (VM) constitute a pivotal neuronal population controlling motor behaviors, cognitive and affective brain functions, which generation critically relies on the activation of Wingless-type MMTV integration site (Wnt)/β-catenin pathway in their progenitors. In Parkinsons disease, DA cell bodies within the substantia nigra pars compacta (SNpc) progressively degenerate, with causes and mechanisms poorly understood. Emerging evidence suggests that Wnt signaling via Frizzled (Fzd) receptors may play a role in different degenerative states, but little is known about Wnt signaling in the adult midbrain. Using in vitro and in vivo model systems of DA degeneration, along with functional studies in both intact and SN lesioned mice, we herein highlight an intrinsic Wnt1/Fzd-1/β-catenin tone critically contributing to the survival and protection of adult midbrain DA neurons. In vitro experiments identifie Fzd-1 receptor expression at a mRNA

The Pax Genes, or Paired-Box Containing Genes, play important roles in the development and proliferation of multiple cell lines, development of organs, and development and organization of the central nervous system.[7] The transcription factor gene Pax2 is important in the regionalized embryological development of the central nervous system. In mammals, the brain is developed in three regions: the forebrain, midbrain, and the hindbrain.[8] Concentration gradients of fibroblast growth factor 8 (FGF8) and Wingless-Type MMTV Integration Site Family, Member 1 (Wnt1) control expression of Pax2 during development of the Mesencephalon, or midbrain.[9] Similar patterning during embryological development can be observed in basal chordates or ascidians, in which organization of the central nervous system in ascidian larvae are also controlled by fibroblast growth factor genes.[8] The Pax2 gene encodes for the transcription factor which appears to be essential in the organization of the midbrain and ...

Results qPCR analysis showed increased expression of the alarmins S100A8/A9 and several members of the canonical Wnt signaling pathway in the CIOA model at all time points measured. In the DMM model, the expression of S100A8/A9 and Wnt16 and WISP1 was mainly increased at day 28 after induction. Kinetics of S100 and Wnt expression were comparable, as was observed in both models. This gave rise to the question if an interrelationship existed between these factors. Therefore, we overexpressed Wnt8a and Wnt16, two canonical Wnts, with the use of adenoviral vectors. However, this did not result in increased expression of S100A8 and S100A9, both on RNA and protein level. In contrast, we found that injection of S100A8 increased the expression of Wnt16 in the synovium and accumulation of β-catenin, a hallmark of canonical Wnt signaling, in both cartilage and synovium. In addition, the downstream mediator of canonical Wnt signaling WISP1, was increased. Furthermore, we found reduced β-catenin ...

TY - JOUR. T1 - Effects of miR-335-5p in modulating osteogenic differentiation by specifically downregulating Wnt antagonist DKK1. AU - Zhang, Jin. AU - Tu, Qisheng. AU - Bonewald, Lynda F.. AU - He, Xi. AU - Stein, Gary. AU - Lian, Jane. AU - Chen, Jake. PY - 2011/8/1. Y1 - 2011/8/1. N2 - Dickkopf-related protein 1 (DKK1) is essential to maintain skeletal homeostasis as an inhibitor of Wnt signaling and osteogenic differentiation. The purpose of this study was to investigate the molecular mechanisms underlying the developmental stage-specific regulation of the DKK1 protein level. We performed a series of studies including luciferase reporter assays, micro-RNA microarray, site-specific mutations, and gain- and loss-of-function analyses. We found that the DKK1 protein level was regulated via DKK1 3 UTR by miRNA control, which was restricted to osteoblast-lineage cells. As a result of decreased DKK1 protein level by miR-335-5p, Wnt signaling was enhanced, as indicated by elevated GSK-3β ...

WNT5B antibody, Internal (wingless-type MMTV integration site family, member 5B) for FACS, IHC-P, WB. Anti-WNT5B pAb (GTX81146) is tested in Human, Mouse samples. 100% Ab-Assurance.

WNT16 antibody (wingless-type MMTV integration site family, member 16) for WB. Anti-WNT16 pAb (GTX128468) is tested in Human, Mouse samples. 100% Ab-Assurance.

|strong|Rabbit anti WNT-1 antibody|/strong| recognizes wingless-type MMTV integration site family, member 1 (WNT-1). This protein is highly conserved in evolution and is essential for normal developme…

Background: Dysregulation of WNT signaling has been reported in many malignancies. Objective: This study was conducted to investigate the expression pattern of 14 members of the WNT gene family in different immunophenotypic subtypes of ALL. Methods: Semi-quantitative RT-PCR was performed on samples from 71 ALL patients and 36 age-matched healthy individuals. The ALL patients were categorized into BALL (76%), T-ALL (22.6%) and mixed lineage (1.4%) and the B-ALL cases were further classified into pro-B, pre-BI, pre-BII and immature/mature-B based on immunophenotypic results. Results: Among the WNT genes, WNT-7B (p=0.026), WNT-9A (p=0.020) and WNT-16B (p=0.023) were significantly over-expressed, whereas WNT- 2B (p=0.033), WNT-5A (p=0.016), WNT-7A (p|0.0001) and WNT-10A (p|0.0001) were down-regulated in B-ALL. Among the T-ALL subtype, however, significant down-regulation of WNT-2B, WNT-5B, WNT-7A, WNT-10A and WNT-11 was evident. Comparison between B-ALL subtypes showed significant over-expression of WNT-7B,

Limb-Bud and Heart (LBH) is a novel key transcriptional regulator of vertebrate development. However, the molecular mechanisms upstream of LBH and its role in adult development are unknown. Here we show that in epithelial development, LBH expression is tightly controlled by Wnt signaling. LBH is transcriptionally induced by the canonical Wnt pathway, as evident by the presence of functional TCF/LEF binding sites in the LBH locus and rapid beta-catenin-dependent upregulation of endogenous LBH by Wnt3a. In contrast, LBH induction by Wnt/beta-catenin signaling is inhibited by Wnt7a, which in limb development signals through a non-canonical pathway involving Lmx1b. Furthermore, we show that Lbh is aberrantly overexpressed in mammary tumors of MMTV-Wnt1 transgenic mice and in aggressive basal-subtype human breast cancers that display Wnt/beta-catenin hyperactivation. Deregulation of LBH in human breast cancer appears to be Wnt/beta-catenin dependent as DKK1 and Wnt7a inhibit LBH expression in breast

Background The Wnt signalling pathway is an important regulator of adult tissue maintenance and homeostasis. Disorders in Wnt signaling cause human degenerative diseases as well as cancer. Dickkopf-1 (DKK-1) is negative regulator protein of the Wnt pathway and is associated with a variety of organic diseases. Under the hypothesis that DKK-1 as a regulator protein is involved in ventricular remodelling after myocardial infarction we aimed to investigate the prognostic value of serum measurement of DKK-1 in patients with acute coronary syndromes.. Methods and results From April 2003 until April 2005 1136 consecutive patients (age 64±12 years; 347 females) with an ACS within the last 48 hours, who were referred for early invasive diagnositc were included. Follow up data were available for 1128 (99.3%) patients. Serum samples on admission were available for 1092 (97%) patients and from 820 (72%) patients a second sample the day following admission. Values are expressed as median. Values of DKK-1 on ...

Non-canonical WNT signaling through FZD receptors and/or ROR1/ROR2/RYK co-receptors activates the PCP, RTK or Ca2+ signaling cascades (Fig. 2).. Non-canonical WNT/PCP signaling through FZD receptors and Dishevelled (DVL) adaptor proteins regulates the coordinated cellular orientation within an epithelial plane, collective cell movements during gastrulation and neurulation stages of embryogenesis and directional cell movement during invasion and metastasis of cancer cells (58-62). WNT/PCP signals are converted to actin cytoskeletal dynamics via the small G-proteins RAC and RHO (Fig. 2), and then, RAC and RHO activate JNK-dependent transcription and YAP/TAZ-dependent transcription, respectively (63-66). WNT/PCP signaling regulates actin cytoskeletal dynamics, directional cell movement and JNK- or YAP/TAZ-dependent transcription.. Non-canonical WNT signaling through RTKs, such as ROR1, ROR2 and RYK, activates the PI3K-AKT signaling cascade (29,67-69). ROR1 and ROR2, with the extracellular ...

Wnt proteins form a family of highly conserved secreted signaling molecules that regulate cell-to-cell interactions during embryogenesis. Insights into the mechanisms of Wnt action have emerged from several systems: genetics in Drosophila and Caenorhabditis elegans; biochemistry in cell culture and ectopic gene expression in Xenopus embryos. Mutations in Wnt genes or Wnt pathway components lead to specific developmental defects, while various human diseases, including cancer, are caused by abnormal Wnt signaling. As currently understood, Wnt proteins bind to receptors of the Frizzled and LRP families on the cell surface. Through several cytoplasmic relay components, the signal is transduced to beta-catenin, which enters the nucleus and forms a complex with TCF to activate transcription of Wnt target gene (text from [1] ...

In this report, we show that the Wnt antagonist Dkk-1 suppressed canonical Wnt signaling in bone marrow endosteal cells, suggesting a role for Dkk-1 in the regulation of the bone marrow stem cell niche. Intriguingly, Dkk-1 mobilized vasculogenic progenitor cells without concomitant release of inflammatory cells as compared to G-CSF. These effects are reminiscent of the recently described effect of RANKL.16 Indeed, Dkk-1 induced expression of the osteoclast differentiation factor RANKL and the bone-resorbing protease cathepsin K. Subsequently, the vasculogenic progenitor mobilizing effect of systemically administered Dkk-1 resulted in enhanced neovascularization in the Matrigel plug assay, because higher numbers of GFP+ transgenic bone marrow-derived cells were recruited to newly formed vessels. Therefore, Dkk-1 appears to be a potent regulator of vasculogenic progenitors.. The mechanisms by which Dkk-1 stimulates RANKL expression and mobilization of vasculogenic progenitors may include a direct ...

WNT5B glycoprotein belongs to the Wnt protein family. Limited investigations revealed a possible role of WNT5B in malignancies, such as triple-negative breast cancer and oral squamous cell carcinoma. However, whether WNT5B contributes to the progression of lung adenocarcinoma (LAD) remains unclear. Here, we initially determine that WNT5B is highly expressed in LAD and is positively correlated with lymph node metastasis and TNM stage. Consistently, clinical analysis reveals WNT5B as an independent prognostic biomarker in LAD. Silencing WNT5B suppresses the proliferation of LAD both in vitro and in vivo by interfering G1/S cell-cycle progression and modulating amino acid metabolism, revealing its remarkable oncogenic role in LAD. Of note, we also identified miR-5587-3p as a negative upstream regulator of WNT5B in LAD, which may help develop therapies targeting LAD patients with high WNT5B expression. Taken together, our results revealed an oncogenic role of WNT5B in LAD, which could be a prognostic

TY - JOUR. T1 - Wingless-type mammary tumor virus integration site family, member 5A (Wnt5a) regulates human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein 120 (gp120)-induced expression of pro-inflammatory cytokines via the Ca2+/calmodulin-dependent protein kinase II (CaMKII) and c-Jun N-terminal kinase (JNK) signaling pathways. AU - Li, Bei. AU - Shi, Yuqiang. AU - Shu, Jianhong. AU - Gao, Junling. AU - Wu, Ping. AU - Tang, Shao Jun. PY - 2013/5/10. Y1 - 2013/5/10. N2 - Background: HIV-1 infection causes chronic neuroinflammation in the central nervous system (CNS). Results: The spinal cytokine up-regulation induced by HIV-1 gp120 protein depends on Wnt5a/CaMKII and/or Wnt5a/JNK pathways. Conclusion: gp120 stimulates cytokine expression in the spinal cord dorsal horn by activating Wnt5a signaling. Significance: The finding reveals Wnt signaling-mediated novel mechanisms by which HIV-1 may cause neuroinflammation.. AB - Background: HIV-1 infection causes chronic neuroinflammation ...

TY - JOUR. T1 - Aberrant non-canonical WNT pathway as key-driver of high-grade serous ovarian cancer development. AU - Zannoni, Gian Franco. PY - 2020. Y1 - 2020. N2 - Epithelial ovarian cancer (EOC), the deadliest among gynecologic malignancies, is ranked as the fifth leading cause of cancer deaths in females [1]. Based on morphological findings, cellular origins, clinical characteristics, and several molecular genetic/epigenetic alterations, EOC has been subdivided into five main types: high-grade serous (HGSC, 70%), endometrioid (EC, 10%), clear cell (CC, 10%), mucinous (MC, 3%), and low-grade serous carcinomas (LGSC, , 5%) that account for over 95% of cases [2]. HGSCs generally harbor TP53 alterations, a pronounced genomic instability and, also, inherited and somatic BRCA1 and BRCA2 mutations. The other abovementioned cancer types are frequently characterized by mutations in KRAS, BRAF, PTEN, and CTNNB1 (Beta-catenin), and a relatively stable karyotype [2]. In this complex and heterogeneous ...

Citable URI: http://udspace.udel.edu/handle/19716/19610 Advisor: Jia L. Song. Publisher: University of Delaware. Date Issued: 2016-05. Abstract: The Wnt signaling pathways are highly evolutionarily conserved in regulating cell specification, cell polarity and morphogenesis in development. The non-canonical Wnt pathways (ncWnt) consist of the Wnt/Planar Cell Polarity (Wnt/PCP) and the Wnt/calcium (Wnt/Ca2+) pathways. In all Wnt signaling pathways, Dvl transduces Wnt ligand activation. We hypothesize that perturbation of the Wnt/Ca2+ pathway with drugs will impact the morphogenic movements of primary mesenchyme cells (PMCs), which give rise to the skeleton spicules that facilitate larval swimming and feeding in the sea urchin embryo. To investigate specifically the regulation of ncWnt/Ca2+ pathway on the directed migration of PMCs, we treated sea urchin embryos with inhibitor Cyclosporin A (CsA), activator Phorbol 12-myristate 13-acetate (PMA) and inhibitor KN-93 that disrupt the ncWnt/Ca2+ ...

Wnt signalling has important roles during development and in many diseases. As morphogens, hydrophobic Wnt proteins exert their function over a distance to induce patterning and cell differentiation decisions. Recent studies have identified several factors that are required for the secretion of Wnt proteins; however, how Wnts travel in the extracellular space remains a largely unresolved question. Here we show that Wnts are secreted on exosomes both during Drosophila development and in human cells. We demonstrate that exosomes carry Wnts on their surface to induce Wnt signalling activity in target cells. Together with the cargo receptor Evi/WIs, Wnts are transported through endosomal compartments onto exosomes, a process that requires the R-SNARE Ykt6. Our study demonstrates an evolutionarily conserved functional role of extracellular vesicular transport of Wnt proteins ...

Aberrant activation of Wnt/beta-catenin signaling is recognized as a critical factor in the etiology of colorectal cancer. Evidence has suggested that dysregulated beta-catenin activity is associated with the majority of colon cancers via activation of the expression of Wnt regulated oncogenes. In the nucleus, beta-catenin regulates transcription by recruiting additional coactivators. These coactivators all have distinct and unique functions on Wnt/beta-catenin target gene activation. Here we report two coactivators for beta-catenin-mediated transcription: CCAR1 (Cell Cycle and Apoptosis Regulator 1) and CARM1 (coactivator-associated-protein-arginine-methyltransferase 1). We show that both CCAR1 and CARM1 interact with beta-catenin and positively modulate beta-catenin-mediated gene expression. In colorectal cancer cells, which have constitutively high Wnt/beta-catenin activity, depletion of CCAR1 or CARM1 inhibits the expression of Wnt/beta-catenin-mediated oncogenes and suppresses ...

TY - JOUR. T1 - Wnt antagonist DKK1 acts as a tumor suppressor gene that induces apoptosis and inhibits proliferation in human renal cell carcinoma. AU - Hirata, Hiroshi. AU - Hinoda, Yuji. AU - Nakajima, Koichi. AU - Kawamoto, Ken. AU - Kikuno, Nobuyuki. AU - Ueno, Koji. AU - Yamamura, Soichiro. AU - Zaman, Mohd S.. AU - Khatri, Gaurav. AU - Chen, Yi. AU - Saini, Sharanjot. AU - Majid, Shahana. AU - Deng, Guoren. AU - Ishii, Nobuhisa. AU - Dahiya, Rajvir. N1 - Copyright: Copyright 2011 Elsevier B.V., All rights reserved.. PY - 2011/4/15. Y1 - 2011/4/15. N2 - The functional significance of Wnt antagonist DKK1 has not been investigated in renal cell carcinoma (RCC). Therefore, we hypothesized that DKK1 may be a tumor suppressor gene and is epigenetically silenced, thus decreased DKK1 may cause progression of RCC. To assess the function of DKK1, we established stable DKK1 transfected cells and monitored them regarding cell viability, colony formation, apoptosis, cell cycle, and invasive ...

Although regulators of the Wnt/planar cell polarity (PCP) pathway are widely expressed in vertebrate nervous systems, their roles at synapses are unknown. Here, we show that Vangl2 is a postsynaptic factor crucial for synaptogenesis and that it coprecipitates with N-cadherin and PSD-95 from synapse-rich brain extracts. Vangl2 directly binds N-cadherin and enhances its internalization in a Rab5-dependent manner. This physical and functional interaction is suppressed by β-catenin, which binds the same intracellular region of N-cadherin as Vangl2. In hippocampal neurons expressing reduced Vangl2 levels, dendritic spine formation as well as synaptic marker clustering is significantly impaired. Furthermore, Prickle2, another postsynaptic PCP component, inhibits the N-cadherin-Vangl2 interaction and is required for normal spine formation. These results demonstrate direct control of classic cadherin by PCP factors; this control may play a central role in the precise formation and maturation of cell-cell

TY - JOUR. T1 - Wnt4 expression in the differentiating gonad of the frog Rana rugosa. AU - Oshima, Yuki. AU - Hayashi, Toshiyuki. AU - Tokunaga, Shuichi. AU - Nakamura, Masahisa. PY - 2005/6. Y1 - 2005/6. N2 - Wnt4, a member of the Wnt family, is known to influence the sex-determination cascade. In mice having a targeted deletion of Wnt4, masculinization occurs in XX pups. Therefore, in addition to Sry, Wnt4 is also involved in sex determination in mice. In humans, a chromosomal duplication of the WNT4 causes feminization of XY-individuals. Thus, for better understanding of the mechanism of sex determination in vertebrates, it is necessary to examine the expression of Wnt4 at early gonadal development stages in non-mammalians. We first isolated the Wnt4 cDNA from the tetsis of the frog Rana rugosa. R. rugosa Wnt4 had a high similarity (,86%) at the amino acid level with zebra fish, chicken, mouse, and human Wnt4s. We next employed RT-PCR analysis to examine whether Wnt4 was expressed in a ...

TNF-α is also able to induce insulin signaling defects by acting on adipocytes and muscle cells, impair insulin signaling through inhibition of the tyrosine kinase activity of the insulin receptor, and suppress the secretion from adipocytes of adiponectin, an anti-inflammatory molecule that also functions in regulating insulin sensitivity [ 78, 79 ]. Furthermore, protein wingless-type MMTV integration site family member 5a (wnt5a) levels were shown to be upregulated in psoriatic skin lesions [ 80 ] , source: Psoriasis Cure: Treatments, read here read online Psoriasis Cure: Treatments, Natural Remedies and Best Home Managements (Skin Disease, Skin Problems, Skin Diseases and Disorders Book 1) pdf. I have had the lesions for about 10 years and for the most part they are ugly and dont hurt at all, until now. Now they slough off and drain for days before scabbing over. The last one has drained now for 10 days ref.: Whats Your Assessment? read pdf Whats Your Assessment? book. The skin is rough, ...

MENEZES, Marina de Pádua Nogueira et al. Vias Wnt canônica e não canônica: uma comparação entre o câncer endometrial tipo I e endométrio atrófico no Brasil. Sao Paulo Med. J. [online]. 2011, vol.129, n.5, pp.320-324. ISSN 1516-3180. http://dx.doi.org/10.1590/S1516-31802011000500007.. CONTEXTO E OBJETIVO: A via Wnt está envolvida na tumorigênese de diversos tipos de tecidos. Por essa razão, propusemo-nos a avaliar a expressão de genes da família Wnt no câncer endometrial tipo I. TIPO DE ESTUDO E LOCAL: Estudo transversal com coleta de materiais do banco de tecidos do Departamento de Patologia da Universidade Federal de São Paulo. MÉTODOS: Amostras endometriais foram obtidas de cirurgias que ocorreram entre 1995 e 2005 no Hospital São Paulo, Universidade Federal de São Paulo. Foram separados dois grupos segundo o tipo de tecido obtido: grupo A, com endométrio atrófico (n = 15); e grupo B, com adenocarcinoma endometrial (n = 45). Comparamos a expressão imunoistoquímica de Wnt ...

We analyzed the gene expression patterns of 138 Non-Small Cell Lung Cancer (NSCLC) samples and developed a new algorithm called Coverage Analysis with Fishers Exact Test (CAFET) to identify molecular pathways that are differentially activated in squamous cell carcinoma (SCC) and adenocarcinoma (AC) subtypes. Analysis of the lung cancer samples demonstrated hierarchical clustering according to the histological subtype and revealed a strong enrichment for the Wnt signaling pathway components in the cluster consisting predominantly of SCC samples. The specific gene expression pattern observed correlated with enhanced activation of the Wnt Planar Cell Polarity (PCP) pathway and inhibition of the canonical Wnt signaling branch. Further real time RT-PCR follow-up with additional primary tumor samples and lung cancer cell lines confirmed enrichment of Wnt/PCP pathway associated genes in the SCC subtype. Dysregulation of the canonical Wnt pathway, characterized by increased levels of β-catenin and ...

Purpose: Inhibition of the Wnt signaling pathway has been implicated in the pathogenesis of primary open-angle glaucoma (POAG), but the underlying mechanism remains unclear. We reported that dexamethasone (DEX), a glaucoma-inducing drug, induces glaucomatous cytoskeleton re-arrangement through noncanonical Wnt signaling in cultured trabecular meshwork cells, suggesting the potential role of noncanonical Wnt signaling in POAG pathogenesis. Here, efforts were made to demonstrate that ocular gene transfer of the noncanonical Wnt ligand, Wnt5a, can elicit glaucoma in mice.. Methods: Recombinant adenovirus (AdWnt5a) was injected into the anterior chamber of mice. Intraocular pressure (IOP) was measured by non-invasive tonometer. The enucleated eyes of the experimental mice were subjected to histopathology and immunohistochemistry analysis.. Results: Gene transfer of Wnt5a into the anterior chamber resulted in elevated IOP which is accompanied by the activation of retinal glial cells and the loss of ...

In the chicken basilar papilla it has been reported that overexpression of activated β-catenin induces ectopic HC formation (Stevens et al., 2003) and, more recently, it has been shown that canonical Wnt activation can induce proliferation within dissociated epithelial cells of the avian utricle (Alvarado et al., 2011). The role for this pathway during mammalian cochlear development, however, was unknown. Although multiple transgenic canonical Wnt reporter mice have been generated (listed on the Wnt homepage http://www.stanford.edu/group/nusselab/cgi-bin/wnt/), inconsistencies existed as to the exact spatiotemporal pattern of endogenous Wnt/β-catenin activity (Barolo, 2006). In the inner ear, Qian et al. (Qian et al., 2007) reported no Wnt/β-catenin activity in the otocyst and developing cochlea using the BAT-gal mouse (Maretto et al., 2003), whereas Laine et al. (Laine et al., 2010) identified low-level activity in cochleae of the same BAT-gal strain as well as in the TOP-gal reporter ...

Wnt signaling is normally involved with many areas of vertebrate homeostasis and advancement, like the function and formation of blood vessels cells. between noncanonical and canonical Wnt pathways. Fetal liver organ cells produced from low-density-lipoprotein receptor-related proteins 6-deficient mice (LRP6?/?), generated significantly reduced amounts of MKs in lifestyle of lower ploidy (2N and 4N) than wild-type handles, implicating LRP6-dependent Wnt signaling in MK maturation and proliferation. Finally, in wild-type older murine fetal liver-derived MKs, Wnt3a induced proplatelet development potently, an effect that might be abrogated by DKK1. These data recognize book extrinsic regulators of proplatelet development, and reveal a deep function for Wnt signaling in platelet creation. TIPS Wnt signaling is vital for MK maturation and proliferation furthermore to profoundly rousing proplatelet formation. These observations FMK claim that mature megakaryocytes might be able to react to known Wnt ...

The neural crest is a multipotent cell population that migrates from the dorsal edge of the neural tube to various parts of the embryo where it differentiates into a remarkable variety of different cell types. Initial induction of neural crest is mediated by a combination of BMP, Wnt, FGF, Retinoic acid and Notch/Delta signaling. The two-signal model for neural crest induction suggests that BMP signaling induces the competence to become neural crest. The second signal involves Wnt acting through the canonical pathway and leads to expression of neural crest markers such as slug. Wnt signals from the neural plate, non-neural ectoderm and paraxial mesoderm have all been suggested to play a role in neural crest induction. We show that Xenopus frizzled7 (Xfz7) is expressed in the dorsal ectoderm including early neural crest progenitors and is a key mediator of the Wnt inductive signal. We demonstrate that Xfz7 expression is induced in response to a BMP antagonist, noggin, and that Xfz7 can induce ...

Background Signaling by the Wnt family of secreted glycoproteins through their receptors, the frizzled (Fz) family of seven-pass transmembrane proteins, is critical for numerous cell fate and tissue polarity decisions during development. murine pancreatic insulin-cell migration. Conclusion Our results implicate a conserved role of a Wnt5/Fz2 signaling pathway in islet formation during pancreatic development. This study opens the door for further investigation into a role of Wnt signaling in vertebrate organ development and disease. Background Wnt signaling pathways play important Klf4 functions in both normal development and in the pathogenesis of a variety of diseases, including cancer [1]. Activation of a Wnt signaling pathway requires conversation between a secreted glycoprotein, Wnt, and a seven-pass transmembrane receptor protein, Frizzled (Fz). Different combinations of Wnt and Fz ligand-receptor pairs can transduce at least three distinct kinds of intracellular signaling pathways. The ...

The effect of GSK3 inhibition can be phenocopied both by Wnt3a and by inducible constitutively active beta-catenin, suggesting that the synergy is effected through beta-catenin, the key downstream effector of canonical Wnt signaling. Furthermore, the combined effect of FOXG1 overexpression and GSK3 inhibition on exit from quiescence can be abrogated by Wnt inhibitors.. This effect is present in patient-derived human GSCs and it is abolished by excision of FOXG1. Additionally, we show that the groucho-binding domain of the FOXG1 protein is necessary for the response of human GSCs to GSK3 inhibition, consistent with a putative mechanism whereby FOXG1 may sequester TLE1/groucho, a co-repressor at Wnt target genes.. Finally, we have developed a mouse model of glioblastoma by excision of NF-1 and Pten and overexpression of EGFRvIII in cells with inducible active beta-catenin and FOXG1.. ...

TY - JOUR. T1 - Gli1, downregulated in colorectal cancers, inhibits proliferation of colon cancer cells involving Wnt signalling activation. AU - Akiyoshi, T.. AU - Nakamura, M.. AU - Koga, K.. AU - Nakashima, H.. AU - Yao, T.. AU - Tsuneyoshi, M.. AU - Tanaka, M.. AU - Katano, M.. PY - 2006/7. Y1 - 2006/7. N2 - Background: Early events in the progression of 90% of sporadic colorectal cancers depend on constitutive activation of Wnt signalling. Recent data also indicate a close association between the Hedgehog (Hh) and Wnt pathways in colonic epithelial cell differentiation. Aims: To investigate whether expression of Gli1, a transactivator of Hh signalling, can suppress Wnt signalling and inhibit proliferation of human colorectal cancer cells. Methods: Gli1 and nuclear β-catenin expression were examined in a series of 40 human colorectal cancers by immunohistochemistry. We quantified Gli1 and nuclear β-catenin staining as markers of Hh and Wnt pathway activation, respectively. Two human colon ...

Glypican-3 (GPC3) is a proteoglycan that is bound to the cell surface. It is expressed by most hepatocellular carcinomas (HCCs), but not by normal hepatocytes. GPC3 stimulates HCC growth by promoting canonical Wnt signaling. Because glypicans interact with Wnts, it has been proposed that these proteoglycans stimulate signaling by increasing the amount of Wnt at the cell membrane, facilitating in this way the interaction of this growth factor with its signaling receptor Frizzled. However, in this study we demonstrate that GPC3 plays a more direct role in the stimulation of Wnt signaling. Specifically, we show that, in addition to interacting with Wnt, GPC3 directly binds to Frizzled through its glycosaminoglycan chains, indicating that this glypican stimulates the formation of signaling complexes between these two proteins. Consistent with this, we show that Wnt binding at the cell membrane triggers the endocytosis of a complex that includes Wnt, Frizzled and GPC3. Additional support to our model ...

Rationale: Proper patterning of the atrioventricular canal (AVC) is essential for delay of electrical impulses between atria and ventricles, and defects in AVC maturation can result in congenital heart disease. Objective: To determine the role of canonical Wnt signaling in the myocardium during AVC development. Methods and Results: We utilized a novel allele of β-catenin that preserves β-catenins cell adhesive functions but disrupts canonical Wnt signaling, allowing us to probe the effects of Wnt loss of function independently.¬ We show that loss of canonical Wnt signaling in the myocardium results in tricuspid atresia with hypoplastic right ventricle associated with loss of AVC myocardium. In contrast, ectopic activation of Wnt signaling was sufficient to induce formation of ectopic AV junction-like tissue as assessed by morphology, gene expression, and electrophysiologic criteria. Aberrant AVC development can lead to ventricul¬¬ar preexcitation, a characteristic feature of ...

Wnt signalling controls the balance between stem cell proliferation and differentiation and patterning throughout development. Non-canonical Wnts, such as Wnt5a or Wnt11, enhance cardiac gene expression of endothelial progenitor cells (EPC), mesenchymal stem cells (MSC) and bone marrow mononuclear cells suggesting that non-canonical Wnts regulate cardiac commitment. However, the underlying mechanism is unclear. Using microarray analysis of Wnt5a-induced gene expression in EPC, we discovered that Wnt5a (1.0 μM, 24hours) significantly increased a variety of enzymes, which play key roles in epigenetic remodelling by modifying histone acetylation and methylation. Specifically, JMJD2B (205%), REST (311%), HDAC5 and HDAC7A (716 and 381%), YY1 (304%), and PCGF2 (352%), were significantly increased by Wnt5a. Wnt5a induced up-regulation of JMJD2B in EPC and MSC was further confirmed by real-time RT-PCR. The member of the JmjC-domain containing family, JMJD2B was recently shown to demethylate ...

Osteoarthritis (OA) is a degenerative joint disease involving both cartilage and synovium. The canonical Wnt/β-catenin pathway, which is activated in OA, is emerging as an important regulator of tissue repair and fibrosis. This study seeks to examine Wnt pathway effects on synovial fibroblasts and articular chondrocytes as well as the therapeutic effects of Wnt inhibition on OA disease severity. Mice underwent destabilization of the medial meniscus surgery and were treated by intra-articular injection with XAV-939, a small-molecule inhibitor of Wnt/β-catenin signaling. Wnt/β-catenin signaling was highly activated in murine synovial fibroblasts as well as in OA-derived human synovial fibroblasts. XAV-939 ameliorated OA severity associated with reduced cartilage degeneration and synovitis in vivo. Wnt inhibition using mechanistically distinct small-molecule inhibitors, XAV-939 and C113, attenuated the proliferation and type I collagen synthesis in synovial fibroblasts in vitro but did not ...

TY - JOUR. T1 - Battle in stem cell niches. T2 - Canonical versus noncanonical Wnt signaling. AU - Chen, Sisi. AU - Liu, Yan. PY - 2018/3. Y1 - 2018/3. KW - HSC aging. KW - adult hematopoiesis. KW - canonical Wnt signaling. KW - fetal hematopoiesis. KW - noncanonical Wnt signaling. UR - http://www.scopus.com/inward/record.url?scp=85041374955&partnerID=8YFLogxK. UR - http://www.scopus.com/inward/citedby.url?scp=85041374955&partnerID=8YFLogxK. U2 - 10.1002/JLB.2CE1117-453RR. DO - 10.1002/JLB.2CE1117-453RR. M3 - Editorial. C2 - 29393968. AN - SCOPUS:85041374955. VL - 103. SP - 377. EP - 379. JO - Journal of Leukocyte Biology. JF - Journal of Leukocyte Biology. SN - 0741-5400. IS - 3. ER - ...

Aberrant beta-catenin expression as determined by assessment of its subcellular localization constitutes a surrogate marker of Wnt signalling pathway activation and has been reported in a subset of breast cancers. The association of beta-catenin/Wnt pathway activation with clinical outcome and the mechanisms leading to its activation in breast cancers still remain a matter of controversy. The aims of this study were to address the distribution of beta-catenin expression in invasive breast cancers, the correlations between beta-catenin expression and clinicopathological features and survival of breast cancer patients, and to determine whether aberrant beta-catenin expression is driven by CTNNB1 (beta-catenin encoding gene) activating mutations. Immunohistochemistry was performed on a tissue microarray containing 245 invasive breast carcinomas from uniformly treated patients, using two anti-beta-catenin monoclonal antibodies. Selected samples were subjected to CTNNB1 exon 3 mutation analysis by ...

TY - JOUR. T1 - Change in gene expression profiles of secreted frizzled-related proteins (SFRPs) by sodium butyrate in gastric cancers. T2 - Induction of promoter demethylation and histone modification causing inhibition of Wnt signaling. AU - Shin, Hyunsoo. AU - Kim, Jie Hyun. AU - Lee, Yeo Song. AU - Lee, Yong Chan. PY - 2012/5/1. Y1 - 2012/5/1. N2 - Activation of Wnt signaling without mutation of β-catenin or APC occurs frequently in human gastric cancers. Secreted frizzled-related protein (SFRP), a negative modulator of the Wnt signaling pathway, are frequently inactivated in human gastric cancers. Inhibition of SFRP gene expression may account for the Wnt/β-catenin activation in human gastric cancer. However, the molecular mechanisms of silencing of SFRP genes are not fully understood. Sodium butyrate, a histone deacetylase (HDAC) inhibitor, is known to exhibit anti-cancer effects partly through the differentiation of various cancer cells. In the present study, we investigated: i) the ...

Transgenic mice express Cre recombinase under the control of the mouse wingless-related MMTV integration site 7A protein (|i|Wnt7a|/I|). Cre recombinase expression is found in uterine luminal and glandular epithelial cells as well as other developmental processes. When used with a |i|loxP|/i|-flanked estrogen receptor allele, this mutant mouse strain may be useful in studies of female fertility and estrogen receptor function in uterine tissue.

PubMed ID: 23982892 Albring KF, Weidemüller J, Mittag S, Weiske J, Friedrich K, Geroni MC, Lombardi P, Huber O. Biofactors 2013. Aberrant activation of the canonical Wnt/β-catenin signaling pathway has been reported for numerous tumors of different origins. In most cases, mutations in components of the Wnt signaling pathway or in β-catenin itself were detected which ultimately induce a genetic program that promotes cell proliferation and attenuates apoptosis. Thus, targeting of Wnt/β-catenin signaling is of specific therapeutic interest. Herein, we investigated the plant-derived isoquinoline alkaloid berberine, which has been reported to have anticancer activity, and synthetic 13-arylalkyl derivatives thereof for their effects on Wnt/β-catenin signaling. Berberine did not show major effects on viability of HEK-293 embryonic kidney and HCT116 colon carcinoma cells and was not toxic in concentrations up to 20 µM. Berberine inhibited β-catenin transcriptional activity and attenuated ...

Wnt signaling functions repeatedly during embryonic development to induce different but specific responses. What molecular mechanisms ensure that Wnt signaling triggers the correct tissue-specific response in different tissues? Early Xenopus development is an ideal model for addressing this fundamental question, since there is a dramatic change in the response to Wnt signaling at the onset of zygotic gene transcription: Wnt signaling components encoded by maternal mRNA establish the dorsal embryonic axis; zygotically expressed Xwnt-8 causes almost the opposite, by promoting ventral and lateral and restricting dorsal mesodermal development. Although Wnt signaling can function through different signal transduction cascades, the same beta-catenin-dependent, canonical Wnt signal transduction pathway mediates Wnt signaling at both stages of Xenopus development. Here we show that, while the function of the transcription factor XTcf-3 is required for early Wnt signaling to establish the dorsal ...

The HMG-box factor Tcf1 is required during T-cell development in the thymus and mediates the nuclear response to Wnt signals. Tcf1(-/-) mice have previously been characterized and show developmental blocks at the CD4-CD8- double negative (DN) to CD4+CD8+ double positive transition. Due to the blocks in T-cell development, Tcf1(-/-) mice normally have a very small thymus. Unexpectedly, a large proportion of Tcf1(-/-) mice spontaneously develop thymic lymphomas with 50% of mice developing a thymic lymphoma/leukemia at the age of 16 wk. These lymphomas are clonal, highly metastatic, and paradoxically show high Wnt signaling when crossed with Wnt reporter mice and have high expression of Wnt target genes Lef1 and Axin2. In wild-type thymocytes, Tcf1 is higher expressed than Lef1, with a predominance of Wnt inhibitory isoforms. Loss of Tcf1 as repressor of Lef1 leads to high Wnt activity and is the initiating event in lymphoma development, which is exacerbated by activating Notch1 mutations. Thus, Notch1 and

This perspective tackles the issues facing developmental biologists and cell biologists regarding how the molecular mechanisms for specifying cell fate are defined. This perspective focuses on members of the Wnt family. The author proposes that Wnt proteins may act as stabilizing signals for earlier inductive events in certain systems, for example, in Caenorhabditis elegans during the migration of two neurons and in Drosophila melanogaster during the patterning of the wing.

Fig. 4. G3BP2 regulates LRP6 phosphorylation. (A) F9 cells were treated with either control siRNA or G3BP2-specific siRNA for 24 hours, followed by another round of transfection with either control vector or LRPΔN plasmid. After 24 hours, the cells were stimulated with Wnt3a (10 ng/ml) or left unstimulated for 7 hours and the lysates were assayed for Lef/Tcf-sensitive gene transcription. Values are means ± s.e.m. from three independent experiments. *P,0.05; **P,0.01; versus control (−Wnt3a), ##P,0.01; versus control (+Wnt3a). (B,C) F9 cells were treated with either G3BP2-specific siRNA (B) or G3BP1-specific siRNA (C). After 48 hours, the cells were stimulated with Wnt3a (20 ng/ml) for 30 minutes and the cells were then lysed. The lysates were later assayed for phosphorylated LRP6 (p-LRP6). Upper panel: mean values ± s.e.m. obtained from three independent experiments; lower panel: representative blots. **P,0.01; versus control (−Wnt3a). ##P,0.01; versus control (+ Wnt3a). (D,E) F9 cells ...

TY - JOUR. T1 - Wingless/Wnt signal transduction requires distinct initiation and amplification steps that both depend on Arrow/LRP. AU - Baig-Lewis, Shahana. AU - Peterson-Nedry, Wynne. AU - Wehrli, Marcel. PY - 2007/6/1. Y1 - 2007/6/1. N2 - Members of the Wg/Wnt family provide key intercellular signals during embryonic development and in the maintenance of homeostatic processes, but critical aspects of their signal transduction pathways remain controversial. We have found that canonical Wg signaling in Drosophila involves distinct initiation and amplification steps, both of which require Arrow/LRP. Expressing a chimeric Frizzled2-Arrow protein in flies that lack endogenous Wg or Arrow showed that this construct functions as an activated Wg receptor but is deficient in signal amplification. In contrast, a chimeric Arrow protein containing the dimerization domain of Torso acted as a potent amplifier of Wg signaling but could not initiate Wg signaling on its own. The two chimeric proteins ...

Wnt genes belong to a multigene family encoding secreted proteins that activate receptor-mediated signal transduction pathways involved in both development and disease. The best-understood Wnt pathway is the Wnt/β-catenin pathway. In this pathway, the Wnt signal leads to activation of the nuclear functions of β-catenin, which in turn activates gene expression leading to cell survival, proliferation, or differentiation. A second vertebrate Wnt pathway, the Wnt/Ca2+ pathway, promotes intracellular Ca2+ release and regulates cell movements in development and in some cancers. We have three goals in studying Wnts. Our first goal is to understand the normal functions of Wnt pathways in vertebrates, focusing on regeneration and response to injury. Our second goal is to understand the biochemistry of a Wnt signal. Our third goal is to leverage this understanding of the normal biology of Wnts to determine whether Wnt signaling is involved in various injuries and diseases and, if it is, to make ...

The WNT signalling pathway controls many developmental processes and plays a key role in maintenance of intestine renewal and homeostasis. Glycogen Synthase Kinase 3 (GSK3) is an important component of the WNT pathway and is involved in regulating β-catenin stability and expression of WNT target genes. The mechanisms underpinning GSK3 regulation in this context are not completely understood, with some evidence suggesting this occurs through inhibitory N-terminal serine phosphorylation in a similar way to GSK3 inactivation in insulin signaling. To investigate this in a physiologically relevant context, we have analysed the intestinal phenotype of GSK3 knockin mice in which N-terminal serines 21/9 of GSK3α/β have been mutated to non-phosphorylatable alanine residues. We show that these knockin mutations have very little effect on overall intestinal integrity, cell lineage commitment, β-catenin localization or WNT target gene expression although a small increase in apoptosis at villi tips is ...

TY - JOUR. T1 - AIMP2 controls intestinal stem cell compartments and tumorigenesis by modulating Wnt/β-catenin signaling. AU - Yum, Min Kyu. AU - Kang, Jong Seol. AU - Lee, Al Eum. AU - Jo, Young Woo. AU - Seo, Ji Yun. AU - Kim, Hyun A.. AU - Kim, Yoon Young. AU - Seong, Jinwoo. AU - Lee, Eun Byul. AU - Kim, Ji Hoon. AU - Han, Jung Min. AU - Kim, Sunghoon. AU - Kong, Young Yun. PY - 2016/8/1. Y1 - 2016/8/1. N2 - Wnt/β-catenin (CTNNB1) signaling is crucial for the proliferation and maintenance of intestinal stem cells (ISC), but excessive activation leads to ISC expansion and eventually colorectal cancer. Thus, negative regulators are required to maintain optimal levels of Wnt/β-catenin signaling. Aminoacyl-tRNA synthetase-interacting multifunctional proteins (AIMP) function in protein synthesis, but have also been implicated in signaling cascades affecting angiogenesis, immunity, and apoptosis. In this study, we investigated the relationship between AIMP2 and Wnt/β-catenin signaling in a ...

In this report, we have begun to dissect the nature of target gene expression promoted by the wnt/β-catenin pathway in CaP cells, in vitro. This general question is of relevance to the CaP field, as this pathway has been linked previously to certain aspects of this disease (1) . Focus was drawn toward the expression, although still putative, of real β-catenin target genes in CaP cells; we have demonstrated previously that β-catenin can potentiate TCF-mediated transcription from artificial reporter plasmids in these cells (18 , 22) , thereby providing both a premise and basic framework for broaching the present topic. cDNA microarrays, which have become a main tool in our laboratory for analyzing differential gene expression in prostate tissue (30 , 58) , were used to probe this question, and in doing so, uncovered certain genes of which the mRNA is elevated in a manner associated with increased β-catenin activation. The putative targets highlighted in our report, AhR and TMEM2, were ...

Human mesenchymal stem cells (hMSCs) from bone marrow are a source of osteoblast progenitors in vivo, and under appropriate conditions they differentiate into osteoblasts ex vivo. The cells provide a convenient cell culture model for the study of osteogenic tissue repair in an experimentally accessible system. Recent advances in the field of skeletal development and osteogenesis have demonstrated that signaling through the canonical wingless (Wnt) pathway is critical for the differentiation of progenitor cell lines into osteoblasts. Inhibition of such signals can predispose hMSCs to cell cycle entry and prevent osteogenesis. Our investigation of the role of Wnt signaling in osteogenesis by hMSCs ex vivo has demonstrated that osteogenesis proceeds in response to bone morphogenic protein 2 stimulation and is sustained by Wnt signaling. In the presence of Dkk-1, an inhibitor of Wnt signaling, the cascade is disrupted, resulting in inhibition of osteogenesis. Peptide mapping studies have provided peptide

Members of the Frizzled family of seven-pass transmembrane proteins serve as receptors for Wnt signalling proteins. Wnt proteins have important roles in the differentiation and patterning of diverse tissues during animal development, and inappropriate activation of Wnt signalling pathways is a key f …

Going from posterior to anterior at the L1 larval stage, the Wnt gene expressed in the most posterior domain is lin-44, with prominent expression in the tail hypodermal cells hyp8, hyp9, hyp10 and hyp11 (Harterink et al., 2011; Herman et al., 1995). In addition, lin-44 mRNA is present in the rectal epithelial cells B and Y, showing that lin-44 has a more anterior expression domain than has been observed with reporter transgenes. At later larval stages, lin-44 is also expressed in the phasmid socket cells PHso1 and PHso2 and in the anchor cell (Herman et al., 1995; Inoue et al., 2004). Moving anteriorly, the next posterior Wnt gene is egl-20, with expression in the rectal epithelial cells K, F, U and B, the anal depressor muscle, and P11/12 (Pan et al., 2006; Whangbo and Kenyon, 1999). In addition, egl-20 mRNA is detected in the posterior ventral body wall muscle quadrants VL23 and VR24, and the rectal epithelial cell Y (Harterink et al., 2011). The third Wnt expression domain is occupied by ...

A variety of signals governing early extension, guidance, and connectivity of olfactory receptor neuron (ORN) axons has been identified; however, little is known about axon-mesoderm and forebrain (FB)-mesoderm signals. Using Wnt-ßcatenin reporter mice, we identify a novel Wnt-responsive resident cell population, located in a Frizzled7 expression domain at the surface of the embryonic FB, along the trajectory of incoming ORN axons. Organotypic slice cultures that recapitulate olfactory-associated Wnt-ßcatenin activation show that the ßcatenin response depends on a placode-derived signal(s). Likewise, in Dlx5-/- embryos, in which the primary connections fail to form, Wnt-ßcatenin response on the surface of the FB is strongly reduced. The olfactory placode expresses a number of ßcatenin-activating Wnt genes, and the Frizzled7 receptor transduces the canonical Wnt signal; using Wnt expression plasmids we show that Wnt5a and Wnt7b are sufficient to rescue ßcatenin activation in the absence of ...

Dickkopf-1 (Dkk1), which inhibits canonical Wnt/β-catenin signaling by binding to the Wnt coreceptors LDL-related protein 5 (LRP5) and LRP6 through its carboxy-terminal cysteine-rich domain (C1), induces heart and head cell fates in Xenopus laevis embryos more potently than do other Wnt antagonists, suggesting that it may have additional roles. Korol et al. report that the amino-terminal cysteine-rich domain (N1) of Dkk1 is required for its maximal induction of cell fate and functions independently of canonical Wnt signaling. Overexpression of Dkk1 alone induces ectopic cement gland, the most anterior structure in the embryo, and heart tissues in embryos, and co-overexpression of Dkk1 with a truncated receptor that inhibits bone morphogenetic protein signaling induces the formation of a secondary body axis. When tested in these overexpression assays, the N1 domain did not induce ectopic tissues, the C1 domain induced some ectopic tissues, and N1 + C1 induced more ectopic tissues than C1 alone ...

Synovial sarcoma (SS) is an aggressive soft tissue malignancy of children and young adults, with no effective systemic therapies. Its specific oncogene, SYT-SSX (SS18-SSX), drives sarcoma initiation and development. The exact mechanism of SYT-SSX oncogenic function remains unknown. In a SYT-SSX2 transgenic model, we show that a constitutive Wnt/β-catenin signal is aberrantly activated by SYT-SSX2, and inhibition of Wnt signaling through the genetic loss of β-catenin blocks SS tumor formation. In a combination of cell-based and SS tumor xenograft models, we show that inhibition of the Wnt cascade through co-receptor blockade and the use of small molecule CK1α activators arrests SS tumor growth. We find that upregulation of the Wnt/β-catenin cascade by SYT-SSX2 correlates with its nuclear reprogramming function. These studies reveal the central role of Wnt/β-catenin signaling in SYT-SSX2-induced sarcoma genesis, and open new venues for the development of effective SS curative agents. ...

Activating mutations in the Wnt pathway drive a variety of cancers, but the specific targets and pathways activated by Wnt ligands are not fully understood. To bridge this knowledge gap, we performed a comprehensive time-course analysis of Wnt-dependent signaling pathways in an orthotopic model of Wnt-addicted pancreatic cancer, using a porcupine (PORCN) inhibitor currently in clinical trials, and validated key results in additional Wnt-addicted models. The temporal analysis of the drug-perturbed transcriptome demonstrated direct and indirect regulation of more than 3,500 Wnt-activated genes (23% of the transcriptome). Regulation was both via Wnt/β-catenin and through the modulation of protein abundance of important transcription factors, including MYC, via Wnt-dependent stabilization of proteins (Wnt/STOP). Our study identifies a central role of Wnt/β-catenin and Wnt/STOP signaling in controlling ribosome biogenesis, a key driver of cancer proliferation.. ...

Activating mutations in the Wnt pathway drive a variety of cancers, but the specific targets and pathways activated by Wnt ligands are not fully understood. To bridge this knowledge gap, we performed a comprehensive time-course analysis of Wnt-dependent signaling pathways in an orthotopic model of Wnt-addicted pancreatic cancer, using a porcupine (PORCN) inhibitor currently in clinical trials, and validated key results in additional Wnt-addicted models. The temporal analysis of the drug-perturbed transcriptome demonstrated direct and indirect regulation of more than 3,500 Wnt-activated genes (23% of the transcriptome). Regulation was both via Wnt/β-catenin and through the modulation of protein abundance of important transcription factors, including MYC, via Wnt-dependent stabilization of proteins (Wnt/STOP). Our study identifies a central role of Wnt/β-catenin and Wnt/STOP signaling in controlling ribosome biogenesis, a key driver of cancer proliferation.. ...