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Journal articles on the topic 'WNT5A'

Author: Grafiati

Published: 4 June 2021

Last updated: 25 January 2025

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1

Anido, Urbano, Vanessa Medina Villaamil, Guadalupe Aparicio Gallego, et al. "Analysis of the expression of Wnt signaling ligands in metastatic renal cell carcinomas tissue samples." Journal of Clinical Oncology 30, no. 15_suppl (2012): e15077-e15077. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.e15077.

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e15077 Background: Renal cell carcinomas (RCC) constitute a morphologically and genetically heterogeneous tumor.Wnt proteins are a large family of secreted glycoproteins that activate intracellular signal transduction pathways to control a wide variety of cellular processes such as determination of cell fate, proliferation, migration, and polarity.Wnt signalling may be playing a central role during RCC development. Methods: To characterize Wnt signalling activity in RCC, we gathered 48 tumor samples from patients diagnosed with metastatic RCC between years 2006 and 2011. Expression levels of W

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2

Nemeth, Michael, and David Bodine. "Wnt5a Inhibits Wnt3a-Mediated HSC Differentiation." Blood 106, no. 11 (2005): 2271. http://dx.doi.org/10.1182/blood.v106.11.2271.2271.

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Abstract Activation of the canonical Wnt signaling pathway by Wnt3a has been implicated in hematopoietic stem cell (HSC) self-renewal (Reya et al., Nature, 2003). Wnt5a has been observed to inhibit Wnt3a signaling (Topol et al., J Cell Biol, 2004). We hypothesized that Wnt3a and 5a act as antagonists on HSC function. 1 x 106 lineage negative cells (lin−) were cultured for 4 days in the presence of 50 ng/ml SCF and Flt3L (control) plus 100 ng/ml rmWnt3a and/or 500 ng/ml rmWnt5a (all factors added on day 0 and day 2). Control lin− cell numbers expanded more than lin− cells cultured with Wnt3a, 5

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Abe, Akihiro, Yosuke Niwa, Jinglan Xu, et al. "Analysis of the Role of Wnt Signaling for the Interaction between Leukemia Cells and Stroma." Blood 110, no. 11 (2007): 4314. http://dx.doi.org/10.1182/blood.v110.11.4314.4314.

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Abstract Wnt signaling plays an important role in hematopoietic stem cell self-renewal and proliferation. Recent results also revealed that an aberrant activation of Wnt signaling has been related with hematological malignancies. We have previously reported a stroma-dependent human leukemia cell line, TRL-01, which could not be maintained by any cytokines without stroma or on fibronectin-coated plate although they periodically stimulated the proliferation. We here analyzed the role of Wnt signaling on the cell-adhesion, proliferation and survival of this cell line. TRL-01 was maintained on hum

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4

Bolzoni, Marina, Paola Storti, Daniela Guasco, et al. "The Activation of Wnt5a-Mediated Non Canonical Wnt Signaling in Human Bone Marrow Osteoprogenitor Cells Increases Osteoblastogenesis and Counterbalances the Inhibitory Effect of Myeloma Cells on Ror2/FZD5 Expression,." Blood 118, no. 21 (2011): 3928. http://dx.doi.org/10.1182/blood.v118.21.3928.3928.

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Abstract Abstract 3928 Multiple Myeloma (MM) is characterized by the impairment of osteogenic differentiation of bone marrow (BM) mesenchymal stromal cells (BMSC) and osteoblast suppression. Canonical Wnt signal pathway is critical in the regulation of bone formation. However recent evidences suggest that non-canonical Wnt activation by Wnt5a, rather than canonical one by Wnt3a stimulates the osteogenic properties of BMSC. Non-canonical Wnt signaling, mainly activated by Wnt5a, is transduced through FZD receptor (FDZ5) and Ror2 co-receptor to several cascades such as Disheveled pathways involv

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Ahmad, Samar, and Liliana Attisano. "Wnt5a Promotes Axon Elongation in Coordination with the Wnt–Planar Cell Polarity Pathway." Cells 13, no. 15 (2024): 1268. http://dx.doi.org/10.3390/cells13151268.

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The establishment of neuronal polarity, involving axon specification and outgrowth, is critical to achieve the proper morphology of neurons, which is important for neuronal connectivity and cognitive functions. Extracellular factors, such as Wnts, modulate diverse aspects of neuronal morphology. In particular, non-canonical Wnt5a exhibits differential effects on neurite outgrowth depending upon the context. Thus, the role of Wnt5a in axon outgrowth and neuronal polarization is not completely understood. In this study, we demonstrate that Wnt5a, but not Wnt3a, promotes axon outgrowth in dissoci

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Mastelaro de Rezende, Marina, Giselle Zenker Justo, Edgar Julian Paredes-Gamero, and Reinoud Gosens. "Wnt-5A/B Signaling in Hematopoiesis throughout Life." Cells 9, no. 8 (2020): 1801. http://dx.doi.org/10.3390/cells9081801.

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Wnt signaling is well-known to play major roles in the hematopoietic system, from embryogenesis to aging and disease. In addition to the main β-catenin-dependent pathway, it is now clear that Wnt5a and the structurally related Wnt5b are essential for hematopoiesis, bone marrow colonization and the final steps of hematopoietic stem cell (HSC) maturation via β-catenin-independent signaling. Wnt5a and Wnt5b ligands prevent hematopoietic exhaustion (by maintaining quiescent, long-term HSCs), induce the proliferation of progenitors, and guide myeloid development, in addition to being involved in th

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Minami, Yosuke, Yosuke Niwa, Akihiro Abe, Fumihiko Hayakawa, and Tomoki Naoe. "Wnt Signaling Is Associated with Anti-Apoptosis in the Interaction Between Acute Myeloid Leukemia Cells and Stromal Cells." Blood 120, no. 21 (2012): 1366. http://dx.doi.org/10.1182/blood.v120.21.1366.1366.

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Abstract Abstract 1366 Recent studies have revealed that strength of the Wnt signaling pathway regulates normal hematopoiesis including hematopoietic stem cells, and aberrant activation of the pathway is involved in the development of several types of leukemias. In the bone marrow microenvironment, stromal cells are rich sources of cytokines and some secreted cytokines have been observed to block induction of cell death in myeloid leukemia cells exposed to chemotherapy. Here, we examined the role of the Wnt signaling pathway on cell-adhesion, proliferation and survival of the stroma-dependent

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Nishita, Michiru, Sa Kan Yoo, Akira Nomachi, et al. "Filopodia formation mediated by receptor tyrosine kinase Ror2 is required for Wnt5a-induced cell migration." Journal of Cell Biology 175, no. 4 (2006): 555–62. http://dx.doi.org/10.1083/jcb.200607127.

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The receptor tyrosine kinase Ror2 plays important roles in developmental morphogenesis. It has recently been shown that Ror2 mediates Wnt5a-induced noncanonical Wnt signaling by activating the Wnt–JNK pathway and inhibiting the β-catenin–TCF pathway. However, the function of Ror2 in noncanonical Wnt signaling leading to cell migration is largely unknown. We show, using genetically different or manipulated cultured cells, that Ror2 is critical for Wnt5a-induced, but not Wnt3a-induced, cell migration. Ror2-mediated cell migration requires the extracellular cysteine-rich domain (CRD), which is th

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Mumford, Petey W., Matthew A. Romero, Xuansong Mao, et al. "Cross talk between androgen and Wnt signaling potentially contributes to age-related skeletal muscle atrophy in rats." Journal of Applied Physiology 125, no. 2 (2018): 486–94. http://dx.doi.org/10.1152/japplphysiol.00768.2017.

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We sought to determine whether age-related gastrocnemius muscle mass loss was associated with parallel decrements in androgen receptor (AR) or select Wnt signaling markers. To test this hypothesis, serum-free and total testosterone (TEST) and gastrocnemius AR and Wnt signaling markers were analyzed in male Fischer 344 rats that were 3, 6, 12, 18, and 24 mo (mo) old ( n = 9 per group). Free and total TEST was greatest in 6 mo rats, and AR protein and Wnt5 protein levels linearly declined with aging. There were associations between Wnt5 protein levels and relative gastrocnemius mass ( r = 0.395,

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Pacheco, Ivan I., and R. John MacLeod. "CaSR stimulates secretion of Wnt5a from colonic myofibroblasts to stimulate CDX2 and sucrase-isomaltase using Ror2 on intestinal epithelia." American Journal of Physiology-Gastrointestinal and Liver Physiology 295, no. 4 (2008): G748—G759. http://dx.doi.org/10.1152/ajpgi.00560.2007.

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To understand whether extracellular calcium-sensing receptor (CaSR) expression on colonic myofibroblast cells (18Co) contributed to epithelial homeostasis, we activated the CaSR with 5 mM Ca2+, screened by RT-PCR Wnt family members, and measured their secretion. Transcripts for Wnt 1, 2, 2b, 3a, 4, and 7a were either absent or unchanged whereas Wnt3 decreased and Wnt5a increased. We assessed Wnt5a secretion by Western blot. High Ca2+ (5 mM) substantially increased Wnt5a secretion; small interfering RNA (siRNA) against the CaSR reduced this to constitutive amounts. Expression of Wnt5a plasmid b

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Nemeth, Michael, Yingzi Yang, and David Bodine. "Canonical and Non-Canonical Wnt Signaling Regulate the Balance between HSC Self-Renewal and Differentiation." Blood 108, no. 11 (2006): 862. http://dx.doi.org/10.1182/blood.v108.11.862.862.

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Abstract We and others have implicated activation of canonical Wnt signaling by Wnt3a in promoting hematopoietic stem cell (HSC) self-renewal. Since Wnt5a can inhibit canonical Wnt signaling (Topol, et al. 2003), we hypothesized that Wnt3a and Wnt5a act as antagonists on HSC function. To examine the effect of Wnt3a and Wnt5a on canonical Wnt signaling in HSCs, we isolated HSCs (lin−, c-kitHI, Sca-1HI, IL-7Rα−) that contain a lacZ reporter gene that is induced by canonical signaling and cultured them in serum-free media in the presence of 30 ng/ml SCF and Flt3L and recombinant Wnt3a (3a; 100 ng

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12

Giuliani, Nicola, Simona Colla, Paola Storti, et al. "Activation of Non-Canonical Wnt Pathway in Human Mesenchymal Cells Affects Osteogenic Differentiation: A Potential Target in Multiple Myeloma Microenvironment." Blood 112, no. 11 (2008): 2742. http://dx.doi.org/10.1182/blood.v112.11.2742.2742.

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Abstract Osteoblast suppression is the hallmark of Multiple Myeloma (MM) osteolytic bone lesions mainly due to the capacity of MM cells to inhibit the osteogenic differentiation of bone marrow (BM) mesenchymal cells (MSC). Many evidences suggest that Wnt signaling is critically involved in the regulation of osteoblast formation. Recently, in murine osteoprogenitor cells and in MM mouse models it has been shown that activation of canonical Wnt pathway stimulate osteoblast formation and blunts MM-induced bone destruction. In this study we have investigated whether modulation of both canonical an

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Działo, Edyta, Marcin Czepiel, Karolina Tkacz, Maciej Siedlar, Gabriela Kania та Przemysław Błyszczuk. "WNT/β-Catenin Signaling Promotes TGF-β-Mediated Activation of Human Cardiac Fibroblasts by Enhancing IL-11 Production". International Journal of Molecular Sciences 22, № 18 (2021): 10072. http://dx.doi.org/10.3390/ijms221810072.

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Cardiac fibrosis is a pathological process associated with the development of heart failure. TGF-β and WNT signaling have been implicated in pathogenesis of cardiac fibrosis, however, little is known about molecular cross-talk between these two pathways. The aim of this study was to examine the effect of exogenous canonical WNT3a and non-canonical WNT5a in TGF-β-activated human cardiac fibroblasts. We found that WNT3a and TGF-β induced a β-catenin-dependent response, whereas WNT5a prompted AP-1 activity. TGF-β triggered profibrotic signatures in cardiac fibroblasts, and co-stimulation with WNT

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Działo, Edyta, Michał Rudnik, Roman Koning, et al. "WNT3a and WNT5a Transported by Exosomes Activate WNT Signaling Pathways in Human Cardiac Fibroblasts." International Journal of Molecular Sciences 20, no. 6 (2019): 1436. http://dx.doi.org/10.3390/ijms20061436.

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WNT signaling plays an important role in fibrotic processes in the heart. Recently, exosomes have been proposed as novel extracellular transporters for WNT proteins. In this study, we analyzed whether WNT3a and WNT5a carried by exosomes could activate downstream molecular pathways in human cardiac fibroblasts. Exosomes were isolated from conditioned medium of control, WNT3a- and WNT5a-producing L cells by differential ultracentrifugations. Obtained exosomes showed size ranging between 20–150 nm and expressed exosomal markers ALG-2-interacting protein X (ALIX) and CD63. Treatment with WNT3a-ric

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Liu, Xiangzhou, Wan Chen, You Zhou, Kanglai Tang, and Jiqiang Zhang. "Mechanical Tension Promotes the Osteogenic Differentiation of Rat Tendon-derived Stem Cells Through the Wnt5a/Wnt5b/JNK Signaling Pathway." Cellular Physiology and Biochemistry 36, no. 2 (2015): 517–30. http://dx.doi.org/10.1159/000430117.

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Background/Aims: Tendinopathy is a common sports injury that is manifested by the heterotopic ossification of tendon tissue. Tendon stem cells (TSCs) are prone to osteogenic differentiation under excessive tension. The underlying mechanisms remain poorly understood. Methods: Uniaxial mechanical tension (UMT) served to stretch rat tendon-derived stem cells (rTDSCs) at 8% elongation (frequency: 1 Hz; 48, 60, or 72 hours). Results: The osteogenic differentiation of rTDSCs appeared after UMT along with increased mRNA expression of the osteogenic genes Runx2, Dlx5, Alpl, and Col1a1 and increased Ru

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Bolzoni, Marina, Simona Colla, Paola Storti, et al. "Myeloma Cells Inhibit the Non-Canonical Wnt Co-Receptor Ror2 in Human Mesenchymal/Osteoprogenitor Cells: Effect of Wnt5a/Ror2 Pathway Activation On MM-Induced Impairment of the Osteogenic Differentiation Process." Blood 114, no. 22 (2009): 741. http://dx.doi.org/10.1182/blood.v114.22.741.741.

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Abstract Abstract 741 Osteogenic differentiation of human mesenchymal stem cells (hMSC) is typically impaired in multiple myeloma (MM) patients leading to osteoblast deficiency. Canonical Wnt signal pathway is critical in the regulation of bone formation process and its activation in osteoblastic cells improves bone mass reducing the development of osteolytic lesions in MM mouse model. Together to canonical Wnt signaling, a non-canonical Wnt pathway, independently to β-catenin activation, has been identified. Non-canonical Wnt signaling is transduced through FZD receptor and Ror2 co-receptor t

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Hayashi, K., R. C. Burghardt, F. W. Bazer, and T. E. Spencer. "WNTs in the Ovine Uterus: Potential Regulation of Periimplantation Ovine Conceptus Development." Endocrinology 148, no. 7 (2007): 3496–506. http://dx.doi.org/10.1210/en.2007-0283.

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WNTs (Wingless-type MMTV integration site family member) are involved in critical developmental and growth processes in animals. These studies investigated WNT pathways in the ovine uterus and conceptus during the periimplantation period of pregnancy. WNT2 and WNT2B mRNAs were detected in endometrial stroma. WNT5A and WNT5B mRNAs were most abundant in the stroma and less so in the luminal epithelium, whereas WNT11 mRNA was detected primarily in the glands. WNT7A mRNA was present in the luminal epithelium on d 10, absent on d 12 and 14, and increased between d 16 and 20. Only WNT2, WNT2B, and W

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Chen, Liguang, Li Tang, Tetsu Fukuda, and Thomas J. Kipps. "Expression of ROR1 in Chronic Lymphocytic Leukemia Cells Enhances Cells Survival by Wnt5a Signaling." Blood 110, no. 11 (2007): 340. http://dx.doi.org/10.1182/blood.v110.11.340.340.

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Abstract ROR1 is a type I membrane-receptor tyrosine kinase with intracellular tyrosine kinase domains and extracellular Frizzled-like cysteine-rich domains (CRDs) and kringle domains, which are common to receptors of members of the Wnt-family. We found that ROR1 might serve as an orphan receptor for Wnt5a, which can activate NF-κB via a non-canonical Wnt-signaling pathway. In prior studies we found that CLL cells expressed ROR1 and high-levels of Wnt3, Wnt5b, Wnt6, Wnt10a, Wnt14, and Wnt16, but not Wnt5a, which is found expressed on dendritic cells and other stromal cells that can support leu

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Teofili, Luciana, Maurizio Martini, Eugenia Rosa Nuzzolo, et al. "Defective WNT Signaling and Genetic Profile Of Endothelial Cells In Patients With Low Risk Myelodysplastic Syndromes Suggest a Contribution Of Vascular Niches To Myelodysplasia." Blood 122, no. 21 (2013): 860. http://dx.doi.org/10.1182/blood.v122.21.860.860.

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Abstract Endothelial cells are relevant to normal hematopoiesis. Vascular niches within the bone marrow allow hematopoietic stem cell proliferation and differentiation. In vivo, the contemporary administration of endothelial progenitor cells in BALB/c mice fosters the homing of transplanted hematopoietic cells (Salter et al. Blood 2009; 113:2104). In vitro, the differentiation of CD34+ progenitors is facilitated by the presence of an underlying confluent layer of endothelial colony forming cells (ECFCs Ingram et al. Blood. 2004;104: 2752), even though this effect is highly dependent from the p

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Zhang, Han, Suping Zhang, Emanuela M. Ghia та ін. "Cirmtuzumab Inhibits Non-Canonical Wnt Signaling without Enhancing Canonical Wnt/β-Catenin Signaling in Chronic Lymphocytic Leukemia". Blood 132, Supplement 1 (2018): 2652. http://dx.doi.org/10.1182/blood-2018-99-119606.

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Abstract ROR1 is a receptor tyrosine kinase-like orphan receptor for Wnt5a that is expressed by cells during embryogenesis and by the neoplastic cells of a variety of cancers, including chronic lymphocytic leukemia (CLL). ROR1 can induce activation of β-catenin-independent non-canonical Wnt-signaling. Studies reveal a cross-talk between the non-canonical Wnt-signaling pathway and the β-catenin-dependent canonical Wnt-signaling pathway, which we previously found was also activated in CLL (Lu D, et al, PNAS 101:31118-3123, 2004). Prior studies indicated that silencing a related Wnt5a receptor, R

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Masckauchán, T. Néstor H., Dritan Agalliu, Marina Vorontchikhina, et al. "Wnt5a Signaling Induces Proliferation and Survival of Endothelial Cells In Vitro and Expression of MMP-1 and Tie-2." Molecular Biology of the Cell 17, no. 12 (2006): 5163–72. http://dx.doi.org/10.1091/mbc.e06-04-0320.

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Wnts are lipid-modified secreted glycoproteins that regulate diverse biological processes. We report that Wnt5a, which functions in noncanonical Wnt signaling, has activity on endothelial cells. Wnt5a is endogenously expressed in human primary endothelial cells and is expressed in murine vasculature at several sites in mouse embryos and tissues. Expression of exogenous Wnt5a in human endothelial cells promoted angiogenesis. Wnt5a induced noncanonical Wnt signaling in endothelial cells, as measured by Dishevelled and ERK1/2 phosphorylation, and inhibition of canonical Wnt signaling, a known pro

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Miller, Aunay, Junwen Wang, Joseph Loftus, and Nhan L. Tran. "426 Long non-coding RNA WNT5A-AS1 shows sex-dimorphic differences in survival for males with glioblastoma." Journal of Clinical and Translational Science 6, s1 (2022): 83. http://dx.doi.org/10.1017/cts.2022.247.

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OBJECTIVES/GOALS: The goal of this study is to evaluate the role of WNT5A and WNT5a-AS1 in sex-differences of GBM progression. In our preliminary studies, we found that a long non-coding RNA WNT5A-AS1 is overexpressed in male GBM patients. We also found that WNT5A-AS1s expression shows a negative correlation with overall survival within male patients. METHODS/STUDY POPULATION: We will define the mechanism by which WNT5A-AS1 regulates WNT5a-mediated glioma stem cell (GSC) maintenance by assessing the effects of inhibiting WNT5A-AS1 expression on transcriptional activity and stemness in GSCs. We

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Nagy, Ádám, Márton Tompa, Zoltán Krabóth, Ferenc Garzuly, Alexandra Maráczi, and Bernadette Kálmán. "Wnt pathway markers in low-grade and high-grade gliomas." Ideggyógyászati szemle 74, no. 9-10 (2021): 349–55. http://dx.doi.org/10.18071/isz.74.0349.

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Aberrant activation of the Wnt pathway contributes to differentiation and maintenance of cancer stem cells underlying gliomagenesis. The aim of our research was to determine as to what degrees some Wnt markers are expressed in gliomas of different grades, lineages and molecular subtypes. Nine grade II, 10 grade III and 72 grade IV surgically removed, formalin-fixed paraffin-embedded glioma specimens were included. Mutation status of IDH1 codon 132 was defined by immunohistochemistry and pyrosequencing in all tumors. Grade II and III astrocytic and oligodendroglial tumors were further tested fo

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Xue, Xiang, Xiaoli Li, Jinmeng Yao, Xue Zhang, Xu Ren, and Shan Xu. "Transient and Prolonged Activation of Wnt Signaling Contribute Oppositely to the Pathogenesis of Asherman’s Syndrome." International Journal of Molecular Sciences 23, no. 15 (2022): 8808. http://dx.doi.org/10.3390/ijms23158808.

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Asherman’s Syndrome (AS) is caused by dysfunction of endometrial regenerative ability, which is controlled by adult stem cells and their niche. The Wnt signaling pathway has been demonstrated to be implicated in this process. This study aimed to clarify the relationship between the Wnt signaling pathway and the progression of AS after initial endometrial damage. Endometria with and without adhesion as well as from the intrauterine devices three months after the surgery were collected to compare the area of fibrosis. The area% of fibrosis did not vary significantly. Significantly higher express

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Macaulay, Iain C., Jonathan N. Thon, Marloes R. Tijssen, et al. "Canonical Wnt signaling in megakaryocytes regulates proplatelet formation." Blood 121, no. 1 (2013): 188–96. http://dx.doi.org/10.1182/blood-2012-03-416875.

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Abstract Wnt signaling is involved in numerous aspects of vertebrate development and homeostasis, including the formation and function of blood cells. Here, we show that canonical and noncanonical Wnt signaling pathways are present and functional in megakaryocytes (MKs), with several Wnt effectors displaying MK-restricted expression. Using the CHRF288-11 cell line as a model for human MKs, the canonical Wnt3a signal was found to induce a time and dose-dependent increase in β-catenin expression. β-catenin accumulation was inhibited by the canonical antagonist dickkopf-1 (DKK1) and by the noncan

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Yao, Lingli, Baocun Sun, Xiulan Zhao, et al. "Overexpression of Wnt5a Promotes Angiogenesis in NSCLC." BioMed Research International 2014 (2014): 1–8. http://dx.doi.org/10.1155/2014/832562.

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To evaluate Wnt5a expression and its role in angiogenesis of non-small-cell lung cancer (NSCLC), immunohistochemistry and CD31/PAS double staining were performed to examine the Wnt5a expression and we analyze the relationships between Wnt5a and microvessel density (MVD), vasculogenic mimicry (VM), and some related proteins. About 61.95% of cases of 205 NSCLC specimens exhibited high expression of Wnt5a. Wnt5a expression level was upregulated in the majority of NSCLC tissues, especially in squamous cell carcinoma, while its expression level in adenocarcinoma was the lowest. Wnt5a was also found

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Wakizaka, Kazuki, Toshiya Kamiyama, Tatsuya Orimo, et al. "Role of Wnt5a in suppressing invasiveness of hepatocellular carcinoma via epithelial mesenchymal transition." Journal of Clinical Oncology 38, no. 4_suppl (2020): 573. http://dx.doi.org/10.1200/jco.2020.38.4_suppl.573.

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573 Background: Wnt signaling pathway includes canonical pathway and non-canonical pathway. Wnt/β-Catenin pathway as canonical pathway is associated with the development of hepatocellular carcinoma (HCC). On the other hand, the association between aberrant activation of non-canonical pathway activated by Wnt5a and tumor progression of HCC is not well-known. We investigated the significance of the expression of Wnt5a in HCC. Methods: Immunohistochemical staining of Wnt5a was performed on the specimen of 243 patients who underwent hepatic resection for HCC. We investigated whether the expression

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Chen, Yun, Michael Y. Choi, Liguang Chen, et al. "Cirmtuzumab Blocks Production of Proinflammatory Factors By Inhibiting Wnt5a/ROR1 Induced Activation of NF-Kappa B in Chronic Lymphocytic Leukemia." Blood 132, Supplement 1 (2018): 4415. http://dx.doi.org/10.1182/blood-2018-99-111996.

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Abstract ROR1 is an oncoembryonic receptor tyrosine kinase expressed on chronic lymphocytic leukemia (CLL) B cells, but not on most normal post-partum tissues. It functions as a receptor for Wnt5a, which is present at high levels in the plasma of patients with CLL relative to that of age-matched controls. Wnt5a/ROR1 is known to activate pro-survival signals in CLL cells, but detailed mechanisms are not fully understood. We found that monocyte-derived Nurse-Like Cells (NLC) could induce CLL cells to activate STAT3 (pY705) and that this effect could be blocked by neutralizing antibodies to Wnt5a

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Kobayashi, Yoshie, Takayuki Kadoya, Ai Amioka, et al. "Effect of Wnt5a on aggressiveness of ER-positive breast cancer and cancer cell migration through JNK-ALCAM pathway." Journal of Clinical Oncology 35, no. 15_suppl (2017): 11614. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.11614.

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11614 Background: Wnt5a is a representative ligand that activates β-catenin-independent pathways and involved in cell motility and cell polarity, and the like, being mediated by JNK. We elucidated the implication of Wnt5a expression in breast cancer. Methods: One hundred seventy eight breast cancer patients (mean age ± SD: 60.0 ± 13.2 years) with clinical Stage I-III between January 2011 and February 2014, were prospectively evaluated. We examined relationships between Wnt5a expression and clinicopathological factors by immunohistochemical analyses. 5-year relapse-free survival rates and sites

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Miller, Aunay, Junwen Wang, Joseph Loftus, and Nhan L. Tran. "Abstract 1556: Long non-coding RNA WNT5A-AS1 shows sex-dimorphic differences in survival for males with glioblastoma." Cancer Research 82, no. 12_Supplement (2022): 1556. http://dx.doi.org/10.1158/1538-7445.am2022-1556.

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Abstract Glioblastoma (GBM) is the most common and aggressive primary brain tumor with a median survival time of 12-15 months and 5-year survival rate of 5%. Despite the application of advanced genetics and biological breakthroughs in GBM, the outcome for GBM remains dismal. Previous genome-wide association studies (GWAS) for GBM shows that the incidence rate for GBM in males is 1.6 times higher in men than women, with men displaying overall worse outcomes. In-vivo studies in gender-matched isogenic murine astrocytic cell lines show that the rate of astrocytic transformation is higher in males

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Amioka, Ai, Takayuki Kadoya, Satoshi Sueoka, et al. "Effect of Wnt5a on drug resistance in estrogen receptor-positive breast cancer." Breast Cancer 28, no. 5 (2021): 1062–71. http://dx.doi.org/10.1007/s12282-021-01241-0.

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Abstract Background Previously, we reported that Wnt5a-positive breast cancer can be classified as estrogen receptor (ER)-positive breast cancer; its prognosis is worse than that of Wnt5a-negative breast cancer. This study aimed to investigate the mechanisms underlying the poor prognosis in Wnt5a-positive breast cancer patients. Methods In total, 151 consecutive ER-positive breast cancer patients who underwent resection between January 2011 and February 2014 were enrolled. DNA microarray and pathway analyses were conducted using MCF-7 cells stably expressing Wnt5a [MCF-7/Wnt5a (+)]. Based on t

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Peng, Chunjie, Xiaolei Zhang, Hongli Yu, Donglai Wu, and Jianhua Zheng. "Wnt5a as a Predictor in Poor Clinical Outcome of Patients and a Mediator in Chemoresistance of Ovarian Cancer." International Journal of Gynecologic Cancer 21, no. 2 (2011): 280–88. http://dx.doi.org/10.1097/igc.0b013e31820aaadb.

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Introduction:Wnt5a regulates numerous signaling pathways controlling a wide range of cellular processes, including cell proliferation, differentiation, and apoptosis. However, it is still unclear whether Wnt5a is involved in mediating chemoresistance in cancer. We studied the correlation of Wnt5a expression with clinicopathologic parameters and survival in epithelial ovarian cancer and the effect of Wnt5a expression on chemoresistance of ovarian cancer cells.Methods:Wnt5a expression was immunohistochemically examined in ovarian cancer, benign tumor, and normal ovarian tissues. Two stable cell

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Zeng, Jianxing, Yingying Jing, Qionglan Wu, Jinhua Zeng, Lixin Wei, and Jingfeng Liu. "Autophagy Is Required for Hepatic Differentiation of Hepatic Progenitor Cells via Wnt Signaling Pathway." BioMed Research International 2021 (April 8, 2021): 1–10. http://dx.doi.org/10.1155/2021/6627506.

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The molecular mechanisms regulating differentiation of hepatic progenitor cells (HPCs), which play pivotal roles in liver regeneration and development, remain obscure. Autophagy and Wnt signaling pathways regulate the development and differentiation of stem cells in various organs. However, the roles of autophagy and Wnt signaling pathways in hepatic differentiation of HPCs are not well understood. Here, we describe the effects of autophagy and Wnt signaling pathways during hepatic differentiation of HPCs. We used a well-established rat hepatic progenitor cell line called WB-F344, which was tr

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Al-Qattan, M. M. "WNT pathways and upper limb anomalies." Journal of Hand Surgery (European Volume) 36, no. 1 (2010): 9–22. http://dx.doi.org/10.1177/1753193410380502.

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The various Wnt pathways that are related to upper limb anomalies are reviewed. Abnormalities in the Wnt7a pathway (located in the dorsal ectoderm) produce several clinically relevant conditions such as the palmar duplication syndrome, nail patella syndrome, ulnar ray deficiency, limb hypoplasia, polysyndactyly and the palmar nail syndrome. Abnormalities of the Wnt3/3a pathway (located in the apical ectodermal ridge) include tetra-amelia and loss of the distal phalanges/nails. Abnormalities of the Wnt5/5a pathway (located in the apical ectodermal ridge as well as in the mesoderm) will affect c

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Povinelli, Benjamin, Michael Baranello, Kathleen Kokolus, and Michael Nemeth. "Balanced Wnt5a-Mediated Signaling Is Necessary for Normal Proliferation of Primitive Hematopoietic Cells." Blood 114, no. 22 (2009): 2533. http://dx.doi.org/10.1182/blood.v114.22.2533.2533.

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Abstract Abstract 2533 Poster Board II-510 Multiple members of the Wnt family of ligands have been implicated in the regulation of self-renewal and proliferation of hematopoietic stem cells (HSCs). Previously, we have observed that ex vivo expansion of HSCs in the presence of recombinant murine Wnt5a (rmWnt5a) resulted in increased hematopoietic repopulation. Based on these data, we hypothesized that Wnt5a is necessary for normal function of HSCs and hematopoietic progenitors (HPCs). Since Wnt5a deficiency (Wnt5a−/−) is perinatal lethal in vivo, we tested this hypothesis using in vitro Dexter

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Li, Changgong, Susan M. Smith, Neil Peinado, et al. "WNT5a-ROR Signaling Is Essential for Alveologenesis." Cells 9, no. 2 (2020): 384. http://dx.doi.org/10.3390/cells9020384.

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WNT5a is a mainly “non-canonical” WNT ligand whose dysregulation is observed in lung diseases such as idiopathic pulmonary fibrosis (IPF), chronic obstructive pulmonary disease (COPD) and asthma. Germline deletion of Wnt5a disrupts embryonic lung development. However, the temporal-specific function of WNT5a remains unknown. In this study, we generated a conditional loss-of-function mouse model (Wnt5aCAG) and examined the specific role of Wnt5a during the saccular and alveolar phases of lung development. The lack of Wnt5a in the saccular phase blocked distal airway expansion and attenuated diff

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Zhang, Yanfei, Chen Tu, Dingwei Zhang та ін. "Wnt/β-Catenin and Wnt5a/Ca2+ Pathways Regulate Proliferation and Apoptosis of Keratinocytes in Psoriasis Lesions". Cellular Physiology and Biochemistry 36, № 5 (2015): 1890–902. http://dx.doi.org/10.1159/000430158.

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Background/Aims: Wnt5a is overexpressed in psoriasis lesions, however the mechanism by which Wnt5a is involved in the pathogenesis of psoriasis is not clear. To address this, the expression of Wnt5a in psoriatic lesions and its effect on keratinocyte cell proliferation and apoptosis was examined in vitro. Methods: The expression levels of WNT5A, and genes encoding its receptors frizzled2 (FZD2) and frizzled5 (FZD5) were examined in samples obtained from individuals with psoriasis and healthy controls. Knockdown of Wnt5a with short interfering (si)RNAs was performed in cultured HaCaT keratinocy

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Barbero, Gastón, María Victoria Castro, María Belén Villanueva та ін. "An Autocrine Wnt5a Loop Promotes NF-κB Pathway Activation and Cytokine/Chemokine Secretion in Melanoma". Cells 8, № 9 (2019): 1060. http://dx.doi.org/10.3390/cells8091060.

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Wnt5a signaling has been implicated in the progression of cancer by regulating multiple cellular processes, largely migration and invasion, epithelial-mesenchymal transition (EMT), and metastasis. Since Wnt5a signaling has also been involved in inflammatory processes in infectious and inflammatory diseases, we addressed the role of Wnt5a in regulating NF-κB, a pivotal mediator of inflammatory responses, in the context of cancer. The treatment of melanoma cells with Wnt5a induced phosphorylation of the NF-κB subunit p65 as well as IKK phosphorylation and IκB degradation. By using cDNA overexpre

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Christman, Mark A., Douglas J. Goetz, Eric Dickerson, et al. "Wnt5a is expressed in murine and human atherosclerotic lesions." American Journal of Physiology-Heart and Circulatory Physiology 294, no. 6 (2008): H2864—H2870. http://dx.doi.org/10.1152/ajpheart.00982.2007.

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Atherosclerosis is an inflammatory disease involving the accumulation of macrophages in the intima. Wnt5a is a noncanonical member of the Wnt family of secreted glycoproteins. Recently, human macrophages have been shown to express Wnt5a upon stimulation with bacterial pathogens in vitro and in granulomatous lesions in the lung of Mycobacterium tuberculosis-infected patients. Wnt5a expression has also been liked to Toll-like receptor-4 (TLR-4), an innate immune receptor implicated in atherosclerosis. These observations, along with the fact that Wnt5a is involved in cell migration and proliferat

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Bradley, Elizabeth W., та M. Hicham Drissi. "WNT5A Regulates Chondrocyte Differentiation through Differential Use of the CaN/NFAT and IKK/NF-κB Pathways". Molecular Endocrinology 24, № 8 (2010): 1581–93. http://dx.doi.org/10.1210/me.2010-0037.

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Abstract Although genetic evidence demonstrated a requirement for Wnt5a during cartilage development, little is known about the mechanisms underlying Wnt5a-regulated chondrocyte growth and differentiation. We therefore investigated the signaling pathways by which Wnt5a influences chondrogenesis and differentiation to hypertrophy. Wnt5a treatment of chondroprogenitor cells increased chondrocyte hypertrophy and was associated with an increase in nuclear factor of activated T cells (NFAT) and a decrease in nuclear factor-κB (NF-κB) activation. In contrast, Wnt5a inhibited chondrocyte hypertrophy.

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Huang, Cheng-long, Dage Liu, Jun Nakano, et al. "Wnt5a Expression Is Associated With the Tumor Proliferation and the Stromal Vascular Endothelial Growth Factor—An Expression in Non–Small-Cell Lung Cancer." Journal of Clinical Oncology 23, no. 34 (2005): 8765–73. http://dx.doi.org/10.1200/jco.2005.02.2871.

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Purpose The Wnt gene family encodes the multifunctional signaling glycoproteins. We performed the present study to investigate the clinical significance of Wnt5a expression in non–small-cell lung cancer (NSCLC). Patients and Methods One hundred twenty-three patients with NSCLC who had undergone resection were investigated. Real-time quantitative reverse transcriptase polymerase chain reaction was performed to evaluate the Wnt5a gene expression. Immunohistochemistry was performed to investigate the Wnt5a protein expression, the Ki-67 proliferation index, tumor angiogenesis, and the expression o

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Chakraborty, Arijit, Syamal Roy, Shyam Sundar, and Malini Sen. "Wnt5a signaling antagonizes Leishmania donovani infection." Journal of Immunology 196, no. 1_Supplement (2016): 200.20. http://dx.doi.org/10.4049/jimmunol.196.supp.200.20.

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Abstract Leishmania donovani, the causative agent for visceral leishmaniasis creates a niche within host immune cells to sustain itself. In light of the fact that Wnt5a utilizes a Rac1–NFκB circuitry for sustaining immune homeostasis in macrophages and alters actin assembly (Naskar.et.al 2014, Witze et.al 2008) we deciphered whether there is any influence of Wnt5a signaling on L. donovani infection. Upon infection of macrophages with L.donovani, we noted significant decrease in Wnt5a protein levels. Infection with both SAG sensitive and SAG resistant parasite strains yielded similar results. I

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Elson, Daniel, Christopher Seungwhan Oh, Matthew R. Cring, George F. Widhopf II, and Thomas J. Kipps. "Wnt5a Enhances Chemokine-Directed Migration of T-Cells Made to Express ROR1." Blood 144, Supplement 1 (2024): 5761. https://doi.org/10.1182/blood-2024-211766.

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Successful treatment of patients with chimeric antigen-receptor T-cells (CAR-T) requires effective homing and migration of infused CAR-T cells to the anatomic sites of tumor cells. Such migration typically is directed by T-cell chemokines, e.g. CXCL9/10/11, which may be elaborated at tissue sites of cancer cells bearing the target antigen. We examined whether transduction of T cells to express ROR1 could enhance their chemokine-directed migration. ROR1 is a highly-conserved, developmentally-restricted receptor for Wnt5a, which can induce ROR1-signaling leading to activation of Rho/Rac, ERK1/2,

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Jannesari-Ladani, F., Ghamartaj Hossein, N. Monhasery, S. H. Shahoei, and N. Izadimood. "Wnt5a Influences Viability, Migration, Adhesion, Colony Formation, Eand N-Cadherin Expression of Human Ovarian Cancer Cell Line SKOV-3." Folia Biologica 60, no. 2 (2014): 57–67. http://dx.doi.org/10.14712/fb2014060020057.

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Epithelial ovarian cancer (EOC) cells express Wnt5a, but its role in ovarian cancer progression is poorly defined. The aims of the present study were two-fold: 1) to determine the Wnt5a role in viability, apoptosis, migration, colony formation and adhesion of human serous epithelial ovarian cancer cell line SKOV-3, and 2) to assess the relationship of Wnt5a with Eand N-cadherin in highand low-grade human serous ovarian cancer specimens. Wnt5a over-expression led to 29% increased serum-independent cell viability (P < 0.05) and 35% decreased caspase-3 activity (P < 0.01) compared to SKOV-3

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Jin, Ping, Yi Song, and Guiyuan Yu. "The Role of Abnormal Methylation of Wnt5a Gene Promoter Regions in Human Epithelial Ovarian Cancer: A Clinical and Experimental Study." Analytical Cellular Pathology 2018 (July 16, 2018): 1–9. http://dx.doi.org/10.1155/2018/6567081.

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Objective. In the current study, the role of abnormal methylation of Wnt5a gene promoter regions in human epithelial ovarian cancer was investigated. Methods. Wnt5a expressions were examined by immunohistochemistry in epithelial ovarian tissues (30 normal and 79 human EOC tissues). SKOV3 cells were treated with different concentrations of 5-Aza-CdR (0.5, 5, and 50 μmol/L). The methylation status of the Wnt5a promoter was analyzed using a methylation-specific polymerase chain reaction (MSP), and the expression level of Wnt5a mRNA was detected using quantitative real-time polymerase chain reacti

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Dehghani-Ghobadi, Zeinab, Shahrzad Sheikh Hasani, Ehsan Arefian та Ghamartaj Hossein. "Wnt5A and TGFβ1 Converges through YAP1 Activity and Integrin Alpha v Up-Regulation Promoting Epithelial to Mesenchymal Transition in Ovarian Cancer Cells and Mesothelial Cell Activation". Cells 11, № 2 (2022): 237. http://dx.doi.org/10.3390/cells11020237.

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In this paper, we investigate whether Wnt5A is associated with the TGF-β1/Smad2/3 and Hippo-YAP1/TAZ-TEAD pathways, implicated in epithelial to mesenchymal transition (EMT) in epithelial ovarian cancer. We used 3D and 2D cultures of human epithelial ovarian cancer cell lines SKOV-3, OVCAR-3, CAOV-4, and different subtypes of human serous ovarian cancer compared to normal ovary specimens. Wnt5A showed a positive correlation with TAZ and TGFβ1 in high- and low-grade serous ovarian cancer specimens compared to borderline serous and normal ovaries. Silencing Wnt5A by siRNAs significantly decreased

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Yoon, Sehyoun, Mi-hyun Choi, Min Seok Chang, and Ja-Hyun Baik. "Wnt5a-Dopamine D2 Receptor Interactions Regulate Dopamine Neuron Development via Extracellular Signal-regulated Kinase (ERK) Activation." Journal of Biological Chemistry 286, no. 18 (2011): 15641–51. http://dx.doi.org/10.1074/jbc.m110.188078.

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The dopamine D2 receptor (D2R) plays an important role in mesencephalic dopaminergic neuronal development, particularly coupled with extracellular signal-regulated kinase (ERK) activation. Wnt5a protein is known to regulate the development of dopaminergic neurons. We analyzed the effect of Wnt5a on dopaminergic neuron development in mesencephalic primary cultures from wild-type (WT) and D2R knock-out (D2R−/−) mice. Treatment with Wnt5a increased the number and neuritic length of dopamine neurons in primary mesencephalic neuronal cultures from WT mice, but not from D2R−/− mice. The effect of Wn

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Nishita, Michiru, Sumiyo Itsukushima, Akira Nomachi, et al. "Ror2/Frizzled Complex Mediates Wnt5a-Induced AP-1 Activation by Regulating Dishevelled Polymerization." Molecular and Cellular Biology 30, no. 14 (2010): 3610–19. http://dx.doi.org/10.1128/mcb.00177-10.

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ABSTRACT The receptor tyrosine kinase Ror2 acts as a receptor or coreceptor for Wnt5a to mediate Wnt5a-induced activation of the Wnt/JNK pathway and inhibition of the β-catenin-dependent canonical Wnt pathway. However, little is known about how Ror2 cooperates with another receptor component(s) to mediate Wnt5a signaling. We show here that Ror2 regulates Wnt5a-induced polymerization of Dishevelled (Dvl) and that this Ror2-mediated regulation of Dvl is independent of the cytoplasmic region of Ror2. Ror2 can associate with Frizzled7 (Fz7) via its extracellular cysteine-rich domain to form a rece

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MacLeod, R. John, Madeline Hayes, and Ivan Pacheco. "Wnt5a secretion stimulated by the extracellular calcium-sensing receptor inhibits defective Wnt signaling in colon cancer cells." American Journal of Physiology-Gastrointestinal and Liver Physiology 293, no. 1 (2007): G403—G411. http://dx.doi.org/10.1152/ajpgi.00119.2007.

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To understand the role of the colonic extracellular calcium-sensing receptor (CaSR) in calcium chemoprotection against colon cancer, we activated the CaSR with 5 mM Ca2+ on HT-29 cells, an adenocarcinoma cell line. High Ca2+ stimulated the upregulation (as assessed by RT-PCR) and the secretion of Wnt5a (assessed by Western blot), a noncanonical Wnt family member. Inhibiting CaSR activity with a short interfering RNA (siRNA) duplex against the CaSR reduced CaSR protein and prevented the secretion of Wnt5a. Dominant negative CaSR (R185Q) or siRNA blocked the high Ca2+-mediated inhibition of the

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Guo, Rui, and Quan Sheng Xing. "Roles of Wnt Signaling Pathway and ROR2 Receptor in Embryonic Development: An Update Review Article." Epigenetics Insights 15 (January 2022): 251686572110642. http://dx.doi.org/10.1177/25168657211064232.

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The Wnt family is a large class of highly conserved cysteine-rich secretory glycoproteins that play a vital role in various cellular and physiological courses through different signaling pathways during embryogenesis and tissue homeostasis 3. Wnt5a is a secreted glycoprotein that belongs to the noncanonical Wnt family and is involved in a wide range of developmental and tissue homeostasis. A growing body of evidence suggests that Wnt5a affects embryonic development, signaling through various receptors, starting with the activation of β-catenin by Wnt5a. In addition to affecting planar cell pol

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