WNT5B, a member of the WNT family of proteins that is closely related to WNT5A, is required for cell migration, cell proliferation, or cell differentiation in many cell types. WNT5B signals through the non-canonical β-catenin-independent signaling pathway and often functions as an antagonist of canonical WNT signaling. Although WNT5B has a high amino acid identity with WNT5A and is often assumed to have similar activities, WNT5B often exhibits unique expression patterns and functions. Here, we describe the distinct effects and mechanisms of WNT5B on development, bone, adipose tissue, cardiac tissue, the nervous system, the mammary gland, the lung and hematopoietic cells, compared to WNT5A. We also highlight aberrances in non-canonical WNT5B signaling contributing to diseases such as osteoarthritis, osteoporosis, obesity, type 2 diabetes mellitus, neuropathology, and chronic diseases associated with aging, as well as various cancers.

Center for Cancer Research University of Tennessee Health Science Center Memphis TN United States

Department of Cytokinetics Institute of Biophysics Czech Academy of Sciences Brno Czechia

Department of Experimental Biology Faculty of Science Masaryk University Brno Czechia

Department of Orthopaedic Surgery and Biomedical Engineering University of Tennessee Health Science Center Memphis TN United States

Division of Hematology and Oncology Department of Medicine University of Tennessee Health Science Center Memphis TN United States

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Front Cell Dev Biol. 2021 Jul 23;9:724948. doi: 10.3389/fcell.2021.724948. PubMed

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Abad V., Meyers J. L., Weise M., Gafni R. I., Barnes K. M., Nilsson O., et al. (2002). The role of the resting zone in growth plate chondrogenesis. Endocrinology 143 1851–1857. 10.1210/endo.143.5.8776 PubMed DOI

Agalliu D., Takada S., Agalliu I., McMahon A. P., Jessell T. M. (2009). Motor neurons with axial muscle projections specified by Wnt4/5 signaling. Neuron 61 708–720. 10.1016/j.neuron.2008.12.026 PubMed DOI PMC

Agostino M., Pohl S. O., Dharmarajan A. (2017). Structure-based prediction of Wnt binding affinities for Frizzled-type cysteine-rich domains. J. Biol. Chem. 292 11218–11229. 10.1074/jbc.m117.786269 PubMed DOI PMC

Akoumianakis I., Sanna F., Margaritis M., Badi I., Akawi N., Herdman L., et al. (2019). Adipose tissue-derived WNT5A regulates vascular redox signaling in obesity via USP17/RAC1-mediated activation of NADPH oxidases. Sci. Transl. Med. 11:eaav5055. 10.1126/scitranslmed.aav5055 PubMed DOI PMC

Albanese I., Yu B., Al-Kindi H., Barratt B., Ott L., Al-Refai M., et al. (2017). Role of noncanonical Wnt signaling pathway in human aortic valve calcification. Arterioscler. Thromb. Vasc. Biol. 37 543–552. 10.1161/atvbaha.116.308394 PubMed DOI

Amjadi-Moheb F., Hosseini S. R., Kosari-Monfared M., Ghadami E., Nooreddini H., Akhavan-Niaki H. (2018). A specific haplotype in potential miRNAs binding sites of secreted frizzled-related protein 1 (SFRP1) is associated with BMD variation in osteoporosis. Gene 677 132–141. 10.1016/j.gene.2018.07.061 PubMed DOI

Anderson G., Jenkinson E. J. (2001). Lymphostromal interactions in thymic development and function. Nat. Rev. Immunol. 1 31–40. 10.1038/35095500 PubMed DOI

Andre P., Song H., Kim W., Kispert A., Yang Y. (2015). Wnt5a and Wnt11 regulate mammalian anterior-posterior axis elongation. Development 142, 1516–1527. 10.1242/dev.119065 PubMed DOI PMC

Aoki K., Taketo M. M. (2007). Adenomatous polyposis coli (APC): a multi-functional tumor suppressor gene. J. Cell Sci. 120 3327–3335. 10.1242/jcs.03485 PubMed DOI

Azbazdar Y., Karabicici M., Erdal E., Ozhan G. (2021). Regulation of Wnt signaling pathways at the plasma membrane and their misregulation in cancer. Front. Cell Dev. Biol. 9:631623. 10.3389/fcell.2021.631623 PubMed DOI PMC

Baarsma H. A., Skronska-Wasek W., Mutze K., Ciolek F., Wagner D. E., John-Schuster G., et al. (2017). Noncanonical WNT-5A signaling impairs endogenous lung repair in COPD. J. Exp. Med. 214 143–163. 10.1084/jem.20160675 PubMed DOI PMC

Bailey P., Chang D. K., Nones K., Johns A. L., Patch A. M., Gingras M. C., et al. (2016). Genomic analyses identify molecular subtypes of pancreatic cancer. Nature 531 47–52. PubMed

Bakker E. R., Das A. M., Helvensteijn W., Franken P. F., Swagemakers S., van der Valk M. A., et al. (2013). Wnt5a promotes human colon cancer cell migration and invasion but does not augment intestinal tumorigenesis in Apc1638N mice. Carcinogenesis 34 2629–2638. 10.1093/carcin/bgt215 PubMed DOI

Balciunaite G., Keller M. P., Balciunaite E., Piali L., Zuklys S., Mathieu Y. D., et al. (2002). Wnt glycoproteins regulate the expression of FoxN1, the gene defective in nude mice. Nat. Immunol. 3 1102–1108. 10.1038/ni850 PubMed DOI

Banziger C., Soldini D., Schutt C., Zipperlen P., Hausmann G., Basler K. (2006). Wntless, a conserved membrane protein dedicated to the secretion of Wnt proteins from signaling cells. Cell 125 509–522. 10.1016/j.cell.2006.02.049 PubMed DOI

Bergstein I., Eisenberg L. M., Bhalerao J., Jenkins N. A., Copeland N. G., Osborne M. P., et al. (1997). Isolation of two novel WNT genes, WNT14 and WNT15, one of which (WNT15) is closely linked to WNT3 on human chromosome 17q21. Genomics 46 450–458. 10.1006/geno.1997.5041 PubMed DOI

Bitler B. G., Nicodemus J. P., Li H., Cai Q., Wu H., Hua X., et al. (2011). Wnt5a suppresses epithelial ovarian cancer by promoting cellular senescence. Cancer Res. 71 6184–6194. 10.1158/0008-5472.can-11-1341 PubMed DOI PMC

Blanton S. H., Bertin T., Serna M. E., Stal S., Mulliken J. B., Hecht J. T. (2004). Association of chromosomal regions 3p21.2, 10p13, and 16p13.3 with nonsyndromic cleft lip and palate. Am. J. Med. Genet. A 125A 23–27. 10.1002/ajmg.a.20426 PubMed DOI

Bo H., Gao L., Chen Y., Zhang J., Zhu M. (2016). Upregulation of the expression of Wnt5a promotes the proliferation of pancreatic cancer cells in vitro and in a nude mouse model. Mol. Med. Rep. 13 1163–1171. 10.3892/mmr.2015.4642 PubMed DOI PMC

Bradley E. W., Drissi M. H. (2011). Wnt5b regulates mesenchymal cell aggregation and chondrocyte differentiation through the planar cell polarity pathway. J. Cell. Physiol. 226 1683–1693. 10.1002/jcp.22499 PubMed DOI

Brommage R., Liu J., Hansen G. M., Kirkpatrick L. L., Potter D. G., Sands A. T., et al. (2014). High-throughput screening of mouse gene knockouts identifies established and novel skeletal phenotypes. Bone Res. 2:14034. PubMed PMC

Burn S. F., Webb A., Berry R. L., Davies J. A., Ferrer-Vaquer A., Hadjantonakis A. K., et al. (2011). Calcium/NFAT signalling promotes early nephrogenesis. Dev. Biol. 352 288–298. 10.1016/j.ydbio.2011.01.033 PubMed DOI PMC

Chakravadhanula M., Hampton C. N., Chodavadia P., Ozols V., Zhou L., Catchpoole D., et al. (2015). Wnt pathway in atypical teratoid rhabdoid tumors. Neuro. Oncol. 17 526–535. 10.1093/neuonc/nou229 PubMed DOI PMC

Charoenpanich A., Wall M. E., Tucker C. J., Andrews D. M., Lalush D. S., Dirschl D. R., et al. (2014). Cyclic tensile strain enhances osteogenesis and angiogenesis in mesenchymal stem cells from osteoporotic donors. Tissue Eng. Part A 20 67–78. 10.1089/ten.tea.2013.0006 PubMed DOI PMC

Chen G., Wang Q., Li Z., Yang Q., Liu Y., Du Z., et al. (2020). Circular RNA CDR1as promotes adipogenic and suppresses osteogenic differentiation of BMSCs in steroid-induced osteonecrosis of the femoral head. Bone 133:115258. 10.1016/j.bone.2020.115258 PubMed DOI

Chen Y., Chen Z., Tang Y., Xiao Q. (2021). The involvement of noncanonical Wnt signaling in cancers. Biomed. Pharmacother. 133:110946. 10.1016/j.biopha.2020.110946 PubMed DOI

Cheng R., Sun B., Liu Z., Zhao X., Qi L., Li Y., et al. (2014). Wnt5a suppresses colon cancer by inhibiting cell proliferation and epithelial-mesenchymal transition. J. Cell Physiol. 229 1908–1917. 10.1002/jcp.24566 PubMed DOI

Choi M. R., Jung K. H., Park J. H., Das N. D., Chung M. K., Choi I. G., et al. (2011). Ethanol-induced small heat shock protein genes in the differentiation of mouse embryonic neural stem cells. Arch. Toxicol. 85 293–304. 10.1007/s00204-010-0591-z PubMed DOI

Choudhary P., Dodsworth B. T., Sidders B., Gutteridge A., Michaelides C., Duckworth J. K., et al. (2015). A FOXM1 dependent mesenchymal-epithelial transition in retinal pigment epithelium cells. PLoS One 10:e0130379. 10.1371/journal.pone.0130379 PubMed DOI PMC

Church D. M., Goodstadt L., Hillier L. W., Zody M. C., Goldstein S., She X., et al. (2009). Lineage-specific biology revealed by a finished genome assembly of the mouse. PLoS Biol. 7:e1000112. 10.1371/journal.pbio.1000112 PubMed DOI PMC

Church V., Nohno T., Linker C., Marcelle C., Francis-West P. (2002). Wnt regulation of chondrocyte differentiation. J. Cell Sci. 115 4809–4818. 10.1242/jcs.00152 PubMed DOI

Clevers H., Nusse R. (2012). Wnt/beta-catenin signaling and disease. Cell 149 1192–1205. PubMed

Dahiya S., Saini V., Kumar P., Kumar A. (2019). Insights into molecular interactions of human Wnt5b and Frizzled proteins for their role in teratogenicity. Bioinformation 15 246–254. 10.6026/97320630015246 PubMed DOI PMC

Daudet N., Ripoll C., Moles J. P., Rebillard G. (2002). Expression of members of Wnt and Frizzled gene families in the postnatal rat cochlea. Brain. Res. Mol. Brain Res. 105 98–107. 10.1016/s0169-328x(02)00397-2 PubMed DOI

de Rezende M. M., Ng-Blichfeldt J. P., Justo G. Z., Paredes-Gamero E. J., Gosens R. (2020). Divergent effects of Wnt5b on IL-3- and GM-CSF-induced myeloid differentiation. Cell. Signal. 67:109507. 10.1016/j.cellsig.2019.109507 PubMed DOI PMC

Dejmek J., Safholm A., Kamp Nielsen C., Andersson T., Leandersson K. (2006). Wnt-5a/Ca2+-induced NFAT activity is counteracted by Wnt-5a/Yes-Cdc42-casein kinase 1alpha signaling in human mammary epithelial cells. Mol. Cell. Biol. 26 6024–6036. 10.1128/mcb.02354-05 PubMed DOI PMC

Dhasmana D., Veerapathiran S., Azbazdar Y., Nelanuthala A. V. S., Teh C., Ozhan G., et al. (2021). Wnt3 is lipidated at conserved cysteine and serine residues in zebrafish neural tissue. Front. Cell Dev. Biol. 9:671218. 10.3389/fcell.2021.671218 PubMed DOI PMC

Dijkgraaf L. C., de Bont L. G. M., Boering G., Liem R. S. B. (1995). The structure, biochemistry, and metabolism of osteoarthritic cartilage: a review of the literature. J. Oral Maxillofac. Surg. 53 1182–1192. 10.1016/0278-2391(95)90632-0 PubMed DOI

Dong J.-J., Ying L., Shi K.-O. (2019). Expression of the Wnt ligands gene family and its relationship to prognosis in hepatocellular carcinoma. Cancer Cell Int. 19:34. 10.1186/s12935-019-0743-z PubMed DOI PMC

Duesterdieck-Zellmer K., Semevolos S., Kinsley M., Riddick T. (2015). Age-related differential gene and protein expression in postnatal cartilage canal and osteochondral junction chondrocytes. Gene Expr. Patterns 17 1–10. 10.1016/j.gep.2014.11.002 PubMed DOI

Enomoto M., Hayakawa S., Itsukushima S., Ren D. Y., Matsuo M., Tamada K., et al. (2009). Autonomous regulation of osteosarcoma cell invasiveness by Wnt5a/Ror2 signaling. Oncogene 28 3197–3208. 10.1038/onc.2009.175 PubMed DOI

Estrada K., Styrkarsdottir U., Evangelou E., Hsu Y. H., Duncan E. L., Ntzani E. E., et al. (2012). Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture. Nat. Genet. 44 491–501. PubMed PMC

Fanto M., Weber U., Strutt D. I., Mlodzik M. (2000). Nuclear signaling by Rac and Rho GTPases is required in the establishment of epithelial planar polarity in the Drosophila eye. Curr. Biol. 10 979–988. 10.1016/s0960-9822(00)00645-x PubMed DOI

Fazzi R., Pacini S., Carnicelli V., Trombi L., Montali M., Lazzarini E., et al. (2011). Mesodermal progenitor cells (MPCs) differentiate into mesenchymal stromal cells (MSCs) by activation of Wnt5/calmodulin signalling pathway. PLoS One 6:e25600. 10.1371/journal.pone.0025600 PubMed DOI PMC

Galli L. M., Barnes T. L., Secrest S. S., Kadowaki T., Burrus L. W. (2007). Porcupine-mediated lipid-modification regulates the activity and distribution of Wnt proteins in the chick neural tube. Development 134 3339–3348. 10.1242/dev.02881 PubMed DOI

Gatica-Andrades M., Vagenas D., Kling J., Nguyen T. T. K., Benham H., Thomas R., et al. (2017). WNT ligands contribute to the immune response during septic shock and amplify endotoxemia-driven inflammation in mice. Blood Adv. 1 1274–1286. 10.1182/bloodadvances.2017006163 PubMed DOI PMC

Gavin B. J., McMahon A. P. (1992). Differential regulation of the Wnt gene family during pregnancy and lactation suggests a role in postnatal development of the mammary gland. Mol. Cell. Biol. 12 2418–2423. 10.1128/mcb.12.5.2418 PubMed DOI PMC

Gavin B. J., McMahon J. A., McMahon A. P. (1990). Expression of multiple novel Wnt-1/int-1-related genes during fetal and adult mouse development. Genes Dev. 4 2319–2332. 10.1101/gad.4.12b.2319 PubMed DOI

Gerdes J. M., Liu Y., Zaghloul N. A., Leitch C. C., Lawson S. S., Kato M., et al. (2007). Disruption of the basal body compromises proteasomal function and perturbs intracellular Wnt response. Nat. Genet. 39 1350–1360. PubMed

Gu Q., Tian H., Zhang K., Chen D., Chen D., Wang X., et al. (2018). Wnt5a/FZD4 mediates the mechanical stretch-induced osteogenic differentiation of bone mesenchymal stem cells. Cell. Physiol. Biochem. 48 215–226. 10.1159/000491721 PubMed DOI

Guder C., Philipp I., Lengfeld T., Watanabe H., Hobmayer B., Holstein T. W. (2006). The Wnt code: cnidarians signal the way. Oncogene 25 7450–7460. 10.1038/sj.onc.1210052 PubMed DOI

Gupta K., Schnell E. (2019). Neuronal network remodeling and Wnt pathway dysregulation in the intra-hippocampal kainate mouse model of temporal lobe epilepsy. PLoS One 14:e0215789. 10.1371/journal.pone.0215789 PubMed DOI PMC

Gutzman J. H., Graeden E., Brachmann I., Yamazoe S., Chen J. K., Sive H. (2018). Basal constriction during midbrain-hindbrain boundary morphogenesis is mediated by Wnt5b and focal adhesion kinase. Biol. Open 7:bio034520. 10.1242/bio.034520 PubMed DOI PMC

Habas R., Kato Y., He X. (2001). Wnt/Frizzled activation of rho regulates vertebrate gastrulation and requires a novel formin homology protein Daam1. Cell 107 843–854. 10.1016/s0092-8674(01)00614-6 PubMed DOI

Harada T., Yamamoto H., Kishida S., Kishida M., Awada C., Takao T., et al. (2017). Wnt5b-associated exosomes promote cancer cell migration and proliferation. Cancer Sci. 108 42–52. 10.1111/cas.13109 PubMed DOI PMC

Hart M., Concordet J. P., Lassot I., Albert I., del los Santos R., Durand H., et al. (1999). The F-box protein beta-TrCP associates with phosphorylated beta-catenin and regulates its activity in the cell. Curr. Biol. 9 207–210. 10.1016/s0960-9822(99)80091-8 PubMed DOI

He F., Xiong W., Yu X., Espinoza-Lewis R., Liu C., Gu S., et al. (2008). Wnt5a regulates directional cell migration and cell proliferation via Ror2-mediated noncanonical pathway in mammalian palate development. Development 135 3871–3879. 10.1242/dev.025767 PubMed DOI PMC

Heijink I. H., de Bruin H. G., Dennebos R., Jonker M. R., Noordhoek J. A., Brandsma C. A., et al. (2016). Cigarette smoke-induced epithelial expression of WNT-5B: implications for COPD. Eur. Respir. J. 48 504–515. 10.1183/13993003.01541-2015 PubMed DOI

Heilmann A., Schinke T., Bindl R., Wehner T., Rapp A., Haffner-Luntzer M., et al. (2013). The Wnt serpentine receptor Frizzled-9 regulates new bone formation in fracture healing. PLoS One 8:e84232. 10.1371/journal.pone.0084232 PubMed DOI PMC

Heller R. S., Dichmann D. S., Jensen J., Miller C., Wong G., Madsen O. D., et al. (2002). Expression patterns of Wnts, Frizzleds, sFRPs, and misexpression in transgenic mice suggesting a role for Wnts in pancreas and foregut pattern formation. Dev. Dyn. 225 260–270. 10.1002/dvdy.10157 PubMed DOI

Hino M., Kamo M., Saito D., Kyakumoto S., Shibata T., Mizuki H., et al. (2016). Transforming growth factor-beta1 induces invasion ability of HSC-4 human oral squamous cell carcinoma cells through the Slug/Wnt-5b/MMP-10 signalling axis. J. Biochem. 159 631–640. 10.1093/jb/mvw007 PubMed DOI PMC

Hopwood B., Tsykin A., Findlay D. M., Fazzalari N. L. (2007). Microarray gene expression profiling of osteoarthritic bone suggests altered bone remodelling, WNT and transforming growth factor-beta/bone morphogenic protein signalling. Arthritis Res. Ther. 9:R100. PubMed PMC

Houschyar K. S., Tapking C., Borrelli M. R., Popp D., Duscher D., Maan Z. N., et al. (2018). Wnt pathway in bone repair and regeneration – what do we know so far. Front. Cell Dev. Biol. 6:170. 10.3389/fcell.2018.00170 PubMed DOI PMC

Huang C. L., Liu D., Nakano J., Ishikawa S., Kontani K., Yokomise H., et al. (2005). Wnt5a expression is associated with the tumor proliferation and the stromal vascular endothelial growth factor–an expression in non-small-cell lung cancer. J. Clin. Oncol. 23 8765–8773. 10.1200/jco.2005.02.2871 PubMed DOI

Huang J., Chen C., Liang C., Luo P., Xia G., Zhang L., et al. (2020). Dysregulation of the Wnt signaling pathway and synovial stem cell dysfunction in osteoarthritis development. Stem Cells Dev. 29 401–413. 10.1089/scd.2019.0260 PubMed DOI

Huang T. C., Lee P. T., Wu M. H., Huang C. C., Ko C. Y., Lee Y. C., et al. (2017). Distinct roles and differential expression levels of Wnt5a mRNA isoforms in colorectal cancer cells. PLoS One 12:e0181034. 10.1371/journal.pone.0181034 PubMed DOI PMC

Hung I. C., Chen T. M., Lin J. P., Tai Y. L., Shen T. L., Lee S. J. (2020). Wnt5b integrates Fak1a to mediate gastrulation cell movements via Rac1 and Cdc42. Open Biol. 10:190273. 10.1098/rsob.190273 PubMed DOI PMC

Hunziker E. B. (1994). Mechanism of longitudinal bone growth and its regulation by growth plate chondrocytes. Microsc. Res. Tech. 28 505–519. 10.1002/jemt.1070280606 PubMed DOI

Hurson C. J., Butler J. S., Keating D. T., Murray D. W., Sadlier D. M., O’Byrne J. M., et al. (2007). Gene expression analysis in human osteoblasts exposed to dexamethasone identifies altered developmental pathways as putative drivers of osteoporosis. BMC Musculoskelet. Disord. 8:12. 10.1186/1471-2474-8-12 PubMed DOI PMC

Imel E. A., DiMeglio L. A., Burr D. B. (2014). “Chapter 16 – metabolic bone diseases,” in Basic and Applied Bone Biology, eds Burr D. B., Allen M. R. (San Diego, CA: Academic Press; ) 317–344.

Iozzo R. V., Eichstetter I., Danielson K. G. (1995). Aberrant expression of the growth factor Wnt-5A in human malignancy. Cancer Res. 55 3495–3499. PubMed

Janovska P., Poppova L., Plevova K., Plesingerova H., Behal M., Kaucka M., et al. (2016). Autocrine signaling by Wnt-5a deregulates chemotaxis of leukemic cells and predicts clinical outcome in chronic lymphocytic leukemia. Clin. Cancer Res. 22 459–469. 10.1158/1078-0432.ccr-15-0154 PubMed DOI PMC

Ji H., Goode R. J., Vaillant F., Mathivanan S., Kapp E. A., Mathias R. A., et al. (2011). Proteomic profiling of secretome and adherent plasma membranes from distinct mammary epithelial cell subpopulations. Proteomics 11 4029–4039. 10.1002/pmic.201100102 PubMed DOI

Jia H. L., Zhou D. S. (2018). Downregulation of microRNA-367 promotes osteoblasts growth and proliferation of mice during fracture by activating the PANX3-mediated Wnt/beta-catenin pathway. J. Cell. Biochem. 10.1002/jcb.28108 [Epub ahead of print]. PubMed DOI

Jiang S., Zhang M., Zhang Y., Zhou W., Zhu T., Ruan Q., et al. (2019). WNT5B governs the phenotype of basal-like breast cancer by activating WNT signaling. Cell Commun. Signal. 17:109. PubMed PMC

Kanazawa A., Tsukada S., Kamiyama M., Yanagimoto T., Nakajima M., Maeda S. (2005). Wnt5b partially inhibits canonical Wnt/beta-catenin signaling pathway and promotes adipogenesis in 3T3-L1 preadipocytes. Biochem. Biophys. Res. Commun. 330 505–510. 10.1016/j.bbrc.2005.03.007 PubMed DOI

Kanazawa A., Tsukada S., Sekine A., Tsunoda T., Takahashi A., Kashiwagi A., et al. (2004). Association of the gene encoding wingless-type mammary tumor virus integration-site family member 5B (WNT5B) with type 2 diabetes. Am. J. Hum. Genet. 75 832–843. 10.1086/425340 PubMed DOI PMC

Karp S. J., Schipani E., St-Jacques B., Hunzelman J., Kronenberg H., McMahon A. P. (2000). Indian hedgehog coordinates endochondral bone growth and morphogenesis via parathyroid hormone related-protein-dependent and -independent pathways. Development 127 543–548. PubMed

Katanaev V., Buestorf S. (2009). Frizzled Proteins are bona fide G protein-coupled receptors. Nat. Preced. 10.1038/npre.2009.2765.1 DOI

Kato S., Hayakawa Y., Sakurai H., Saiki I., Yokoyama S. (2014). Mesenchymal-transitioned cancer cells instigate the invasion of epithelial cancer cells through secretion of WNT3 and WNT5B. Cancer Sci. 105 281–289. 10.1111/cas.12336 PubMed DOI PMC

Katoh M., Katoh M. (2005). Comparative genomics on Wnt5a and Wnt5b genes. Int. J. Mol. Med. 15 749–753. PubMed

Kemp J. P., Medina-Gomez C., Estrada K., St Pourcain B., Heppe D. H., Warrington N. M., et al. (2014). Phenotypic dissection of bone mineral density reveals skeletal site specificity and facilitates the identification of novel loci in the genetic regulation of bone mass attainment. PLoS Genet. 10:e1004423. 10.1371/journal.pgen.1004423 PubMed DOI PMC

Kessenbrock K., Smith P., Steenbeek S. C., Pervolarakis N., Kumar R., Minami Y., et al. (2017). Diverse regulation of mammary epithelial growth and branching morphogenesis through noncanonical Wnt signaling. Proc. Natl. Acad. Sci. U. S. A. 114 3121–3126. 10.1073/pnas.1701464114 PubMed DOI PMC

Khan K., Yu B., Kiwan C., Shalal Y., Filimon S., Cipro M., et al. (2020). The role of Wnt/beta-catenin pathway mediators in aortic valve stenosis. Front. Cell Dev. Biol. 8:862. 10.3389/fcell.2020.00862 PubMed DOI PMC

Kilander M. B., Dahlstrom J., Schulte G. (2014). Assessment of Frizzled 6 membrane mobility by FRAP supports G protein coupling and reveals WNT-Frizzled selectivity. Cell. Signal. 26 1943–1949. 10.1016/j.cellsig.2014.05.012 PubMed DOI

Kitagawa M., Hatakeyama S., Shirane M., Matsumoto M., Ishida N., Hattori K., et al. (1999). An F-box protein, FWD1, mediates ubiquitin-dependent proteolysis of beta-catenin. EMBO J. 18 2401–2410. 10.1093/emboj/18.9.2401 PubMed DOI PMC

Kuhl M., Sheldahl L. C., Malbon C. C., Moon R. T. (2000). Ca(2+)/calmodulin-dependent protein kinase II is stimulated by Wnt and Frizzled homologs and promotes ventral cell fates in Xenopus. J. Biol. Chem. 275 12701–12711. 10.1074/jbc.275.17.12701 PubMed DOI

Kumarasinghe D. D., Sullivan T., Kuliwaba J. S., Fazzalari N. L., Atkins G. J. (2012). Evidence for the dysregulated expression of TWIST1, TGFbeta1 and SMAD3 in differentiating osteoblasts from primary hip osteoarthritis patients. Osteoarthritis Cartilage 20 1357–1366. 10.1016/j.joca.2012.07.005 PubMed DOI

Lecarpentier Y., Schussler O., Hébert J.-L., Vallée A. (2019). Multiple targets of the canonical WNT/β-catenin signaling in cancers. Front. Oncol. 9:1248. 10.3389/fonc.2019.01248 PubMed DOI PMC

Li Q., Chen H. (2012). Silencing of Wnt5a during colon cancer metastasis involves histone modifications. Epigenetics 7 551–558. 10.4161/epi.20050 PubMed DOI PMC

Lickert H., Kispert A., Kutsch S., Kemler R. (2001). Expression patterns of Wnt genes in mouse gut development. Mech. Dev. 105 181–184. 10.1016/s0925-4773(01)00390-2 PubMed DOI

Lin S., Baye L. M., Westfall T. A., Slusarski D. C. (2010). Wnt5b-Ryk pathway provides directional signals to regulate gastrulation movement. J. Cell. Biol. 190 263–278. 10.1083/jcb.200912128 PubMed DOI PMC

Liu H., Mohamed O., Dufort D., Wallace V. A. (2003). Characterization of Wnt signaling components and activation of the Wnt canonical pathway in the murine retina. Dev. Dyn. 227 323–334. 10.1002/dvdy.10315 PubMed DOI

Liu S., Liu Y. P., Huang Z. J., Zhang Y. K., Song A. A., Ma P. C., et al. (2015). Wnt/Ryk signaling contributes to neuropathic pain by regulating sensory neuron excitability and spinal synaptic plasticity in rats. Pain 156 2572–2584. 10.1097/j.pain.0000000000000366 PubMed DOI

Liu X., Chen W., Zhou Y., Tang K., Zhang J. (2015). Mechanical tension promotes the osteogenic differentiation of rat tendon-derived stem cells through the Wnt5a/Wnt5b/JNK signaling pathway. Cell. Physiol. Biochem. 36 517–530. 10.1159/000430117 PubMed DOI

Louwette S., Labarque V., Wittevrongel C., Thys C., Metz J., Gijsbers R., et al. (2012). Regulator of G-protein signaling 18 controls megakaryopoiesis and the cilia-mediated vertebrate mechanosensory system. FASEB J. 26 2125–2136. 10.1096/fj.11-198739 PubMed DOI

Lu B. J., Wang Y. Q., Wei X. J., Rong L. Q., Wei D., Yan C. M., et al. (2012). Expression of WNT-5a and ROR2 correlates with disease severity in osteosarcoma. Mol. Med. Rep. 5 1033–1036. 10.3892/mmr.2012.772 PubMed DOI PMC

Lu D., Zhao Y., Tawatao R., Cottam H. B., Sen M., Leoni L. M., et al. (2004). Activation of the Wnt signaling pathway in chronic lymphocytic leukemia. Proc. Natl. Acad. Sci. U. S. A. 101 3118–3123. 10.1073/pnas.0308648100 PubMed DOI PMC

Lutze G., Haarmann A., Demanou Toukam J. A., Buttler K., Wilting J., Becker J. (2019). Non-canonical WNT-signaling controls differentiation of lymphatics and extension lymphangiogenesis via RAC and JNK signaling. Sci. Rep. 9:4739. PubMed PMC

Maeda K., Kobayashi Y., Udagawa N., Uehara S., Ishihara A., Mizoguchi T., et al. (2012). Wnt5a-Ror2 signaling between osteoblast-lineage cells and osteoclast precursors enhances osteoclastogenesis. Nat. Med. 18 405–412. 10.1038/nm.2653 PubMed DOI

Marsell R., Einhorn T. A. (2011). The biology of fracture healing. Injury 42 551–555. PubMed PMC

Martin V., Valencia A., Agirre X., Cervera J., San Jose-Eneriz E., Vilas-Zornoza A., et al. (2010). Epigenetic regulation of the non-canonical Wnt pathway in acute myeloid leukemia. Cancer Sci. 101 425–432. 10.1111/j.1349-7006.2009.01413.x PubMed DOI PMC

Martineau X., Abed E., Martel-Pelletier J., Pelletier J. P., Lajeunesse D. (2017). Alteration of Wnt5a expression and of the non-canonical Wnt/PCP and Wnt/PKC-Ca2+ pathways in human osteoarthritis osteoblasts. PLoS One 12:e0180711. 10.1371/journal.pone.0180711 PubMed DOI PMC

Matsukawa T., Morita K., Omizu S., Kato S., Koriyama Y. (2018). Mechanisms of RhoA inactivation and CDC42 and Rac1 activation during zebrafish optic nerve regeneration. Neurochem. Int. 112 71–80. 10.1016/j.neuint.2017.11.004 PubMed DOI

Mattes B., Dang Y., Greicius G., Kaufmann L. T., Prunsche B., Rosenbauer J., et al. (2018). Wnt/PCP controls spreading of Wnt/beta-catenin signals by cytonemes in vertebrates. Elife 7:e36953. PubMed PMC

Mazzotta S., Neves C., Bonner R. J., Bernardo A. S., Docherty K., Hoppler S. (2016). Distinctive roles of canonical and noncanonical Wnt signaling in human embryonic cardiomyocyte development. Stem Cell Rep. 7 764–776. 10.1016/j.stemcr.2016.08.008 PubMed DOI PMC

Memarian A., Hojjat-Farsangi M., Asgarian-Omran H., Younesi V., Jeddi-Tehrani M., Sharifian R. A., et al. (2009). Variation in WNT genes expression in different subtypes of chronic lymphocytic leukemia. Leuk. Lymphoma 50 2061–2070. 10.3109/10428190903331082 PubMed DOI

Miller J. R. (2002). The Wnts. Genome Biol. 3:REVIEWS3001. PubMed PMC

Minegishi K., Hashimoto M., Ajima R., Takaoka K., Shinohara K., Ikawa Y., et al. (2017). A Wnt5 activity asymmetry and intercellular signaling via PCP proteins polarize node cells for left-right symmetry breaking. Dev. Cell 40 439–452.e4. PubMed PMC

Mitchell J. A., Chesi A., Elci O., McCormack S. E., Roy S. M., Kalkwarf H. J., et al. (2016). Physical activity benefits the skeleton of children genetically predisposed to lower bone density in adulthood. J. Bone Miner. Res. 31 1504–1512. 10.1002/jbmr.2872 PubMed DOI PMC

Miyazaki A., Sugimoto A., Yoshizaki K., Kawarabayashi K., Iwata K., Kurogoushi R., et al. (2019). Coordination of WNT signaling and ciliogenesis during odontogenesis by piezo type mechanosensitive ion channel component 1. Sci. Rep. 9:14762. PubMed PMC

Morioka K., Tanikawa C., Ochi K., Daigo Y., Katagiri T., Kawano H., et al. (2009). Orphan receptor tyrosine kinase ROR2 as a potential therapeutic target for osteosarcoma. Cancer Sci. 100 1227–1233. 10.1111/j.1349-7006.2009.01165.x PubMed DOI PMC

Nicenboim J., Malkinson G., Lupo T., Asaf L., Sela Y., Mayseless O., et al. (2015). Lymphatic vessels arise from specialized angioblasts within a venous niche. Nature 522 56–61. 10.1038/nature14425 PubMed DOI

Niehrs C. (2012). The complex world of WNT receptor signalling. Nat. Rev. Mol. Cell. Biol. 13 767–779. 10.1038/nrm3470 PubMed DOI

Nusse R., Varmus H. E. (1982). Many tumors induced by the mouse mammary tumor virus contain a provirus integrated in the same region of the host genome. Cell 31 99–109. 10.1016/0092-8674(82)90409-3 PubMed DOI

Okamoto M., Udagawa N., Uehara S., Maeda K., Yamashita T., Nakamichi Y., et al. (2014). Noncanonical Wnt5a enhances Wnt/beta-catenin signaling during osteoblastogenesis. Sci. Rep. 4:4493. PubMed PMC

Paez D., Gerger A., Zhang W., Yang D., Labonte M. J., Benhanim L., et al. (2014). Association of common gene variants in the WNT/beta-catenin pathway with colon cancer recurrence. Pharmacogenomics J. 14 142–150. 10.1038/tpj.2013.20 PubMed DOI

Park H. W., Kim Y. C., Yu B., Moroishi T., Mo J. S., Plouffe S. W., et al. (2015). Alternative Wnt signaling activates YAP/TAZ. Cell 162 780–794. 10.1016/j.cell.2015.07.013 PubMed DOI PMC

Peng C., Zhang X., Yu H., Wu D., Zheng J. (2011). Wnt5a as a predictor in poor clinical outcome of patients and a mediator in chemoresistance of ovarian cancer. Int. J. Gynecol. Cancer 21 280–288. 10.1097/igc.0b013e31820aaadb PubMed DOI

Petrini M., Pacini S., Trombi L., Fazzi R., Montali M., Ikehara S., et al. (2009). Identification and purification of mesodermal progenitor cells from human adult bone marrow. Stem Cells Dev. 18 857–866. 10.1089/scd.2008.0291 PubMed DOI PMC

Qi H., Sun B., Zhao X., Du J., Gu Q., Liu Y., et al. (2014). Wnt5a promotes vasculogenic mimicry and epithelial-mesenchymal transition via protein kinase Calpha in epithelial ovarian cancer. Oncol. Rep. 32 771–779. 10.3892/or.2014.3229 PubMed DOI

Raghavan S., Mehta P., Xie Y., Lei Y. L., Mehta G. (2019). Ovarian cancer stem cells and macrophages reciprocally interact through the WNT pathway to promote pro-tumoral and malignant phenotypes in 3D engineered microenvironments. J. Immunother. Cancer 7:190. PubMed PMC

Ram Makena M., Gatla H., Verlekar D., Sukhavasi S., Pandey M. K., Pramanik K. C. (2019). Wnt/beta-catenin signaling: the culprit in pancreatic carcinogenesis and therapeutic resistance. Int. J. Mol. Sci. 20:4242. 10.3390/ijms20174242 PubMed DOI PMC

Rauner M., Sipos W., Pietschmann P. (2008). Age-dependent Wnt gene expression in bone and during the course of osteoblast differentiation. Age (Dordr) 30 273–282. 10.1007/s11357-008-9069-9 PubMed DOI PMC

Ren J., Han P., Ma X., Farah E. N., Bloomekatz J., Zeng X. I., et al. (2019). Canonical Wnt5b signaling directs outlying Nkx2.5+ mesoderm into pacemaker cardiomyocytes. Dev. Cell 50:e725. PubMed PMC

Rijsewijk F., Schuermann M., Wagenaar E., Parren P., Weigel D., Nusse R. (1987). The drosophila homolog of the mouse mammary oncogene int-1 is identical to the segment polarity gene wingless. Cell 50 649–657. 10.1016/0092-8674(87)90038-9 PubMed DOI

Rios-Esteves J., Haugen B., Resh M. D. (2014). Identification of key residues and regions important for porcupine-mediated Wnt acylation. J. Biol. Chem. 289 17009–17019. 10.1074/jbc.m114.561209 PubMed DOI PMC

Robling A. G., Turner C. H. (2009). Mechanical signaling for bone modeling and remodeling. Crit. Rev. Eukaryot. Gene Expr. 19 319–338. 10.1615/critreveukargeneexpr.v19.i4.50 PubMed DOI PMC

Rochard L., Monica S. D., Ling I. T., Kong Y., Roberson S., Harland R., et al. (2016). Roles of Wnt pathway genes wls, wnt9a, wnt5b, frzb and gpc4 in regulating convergent-extension during zebrafish palate morphogenesis. Development 143 2541–2547. 10.1242/dev.137000 PubMed DOI PMC

Routledge D., Scholpp S. (2019). Mechanisms of intercellular Wnt transport. Development 146:dev176073. 10.1242/dev.176073 PubMed DOI

Saitoh T., Katoh M. (2001). Molecular cloning and characterization of human WNT5B on chromosome 12p13.3 region. Int. J. Oncol. 19 347–351. PubMed

Salpea K. D., Gable D. R., Cooper J. A., Stephens J. W., Hurel S. J., Ireland H. A., et al. (2009). The effect of WNT5B IVS3C>G on the susceptibility to type 2 diabetes in UK Caucasian subjects. Nutr. Metab. Cardiovasc. Dis. 19 140–145. 10.1016/j.numecd.2008.02.009 PubMed DOI

Samanta S., Guru S., Elaimy A. L., Amante J. J., Ou J., Yu J., et al. (2018). IMP3 stabilization of WNT5B mRNA facilitates TAZ activation in breast cancer. Cell Rep. 23 2559–2567. 10.1016/j.celrep.2018.04.113 PubMed DOI PMC

Santiago F., Oguma J., Brown A. M., Laurence J. (2012). Noncanonical Wnt signaling promotes osteoclast differentiation and is facilitated by the human immunodeficiency virus protease inhibitor ritonavir. Biochem. Biophys. Res. Commun. 417 223–230. 10.1016/j.bbrc.2011.11.089 PubMed DOI PMC

Sarin S., Zuniga-Sanchez E., Kurmangaliyev Y. Z., Cousins H., Patel M., Hernandez J., et al. (2018). Role for Wnt signaling in retinal neuropil development: analysis via RNA-seq and in vivo somatic CRISPR mutagenesis. Neuron 98:e108. PubMed PMC

Schaffer A. E., Taylor B. L., Benthuysen J. R., Liu J., Thorel F., Yuan W., et al. (2013). Nkx6.1 controls a gene regulatory network required for establishing and maintaining pancreatic Beta cell identity. PLoS Genet. 9:e1003274. 10.1371/journal.pgen.1003274 PubMed DOI PMC

Schiffman J. D., Hodgson J. G., VandenBerg S. R., Flaherty P., Polley M. Y., Yu M., et al. (2010). Oncogenic BRAF mutation with CDKN2A inactivation is characteristic of a subset of pediatric malignant astrocytomas. Cancer Res. 70 512–519. 10.1158/0008-5472.can-09-1851 PubMed DOI PMC

Sharma R. P., Chopra V. L. (1976). Effect of the wingless (wg1) mutation on wing and haltere development in Drosophila melanogaster. Dev. Biol. 48 461–465. 10.1016/0012-1606(76)90108-1 PubMed DOI

Shi F. L., Ren L. X. (2020). Up-regulated miR-374a-3p relieves lipopolysaccharides induced injury in CHON-001 cells via regulating Wingless-type MMTV integration site family member 5B. Mol. Cell. Probes 51:101541. 10.1016/j.mcp.2020.101541 PubMed DOI

Sisson B. E., Dale R. M., Mui S. R., Topczewska J. M., Topczewski J. (2015). A role of glypican4 and wnt5b in chondrocyte stacking underlying craniofacial cartilage morphogenesis. Mech. Dev. 138 Pt 3 279–290. 10.1016/j.mod.2015.10.001 PubMed DOI PMC

Slusarski D. C., Yang-Snyder J., Busa W. B., Moon R. T. (1997). Modulation of embryonic intracellular Ca2+ signaling by Wnt-5A. Dev. Biol. 182 114–120. 10.1006/dbio.1996.8463 PubMed DOI

Smith A. R., Smith R. G., Pishva E., Hannon E., Roubroeks J. A. Y., Burrage J., et al. (2019). Parallel profiling of DNA methylation and hydroxymethylation highlights neuropathology-associated epigenetic variation in Alzheimer’s disease. Clin. Epigenetics 11:52. PubMed PMC

Smolich B. D., McMahon J. A., McMahon A. P., Papkoff J. (1993). Wnt family proteins are secreted and associated with the cell surface. Mol. Biol. Cell 4 1267–1275. 10.1091/mbc.4.12.1267 PubMed DOI PMC

Spanjer A. I., Baarsma H. A., Oostenbrink L. M., Jansen S. R., Kuipers C. C., Lindner M., et al. (2016). TGF-beta-induced profibrotic signaling is regulated in part by the WNT receptor Frizzled-8. FASEB J. 30 1823–1835. 10.1096/fj.201500129 PubMed DOI

Stamos J. L., Weis W. I. (2013). The beta-catenin destruction complex. Cold Spring Harb. Perspect. Biol. 5:a007898. PubMed PMC

Steinhart Z., Angers S. (2018). Wnt signaling in development and tissue homeostasis. Development 145:dev146589. 10.1242/dev.146589 PubMed DOI

Stewart D. J., Chang D. W., Ye Y., Spitz M., Lu C., Shu X., et al. (2014). Wnt signaling pathway pharmacogenetics in non-small cell lung cancer. Pharmacogenomics J. 14 509–522. 10.1038/tpj.2014.21 PubMed DOI PMC

Strutt D. I., Weber U., Mlodzik M. (1997). The role of RhoA in tissue polarity and Frizzled signalling. Nature 387 292–295. 10.1038/387292a0 PubMed DOI

Suomalainen M., Thesleff I. (2010). Patterns of Wnt pathway activity in the mouse incisor indicate absence of Wnt/beta-catenin signaling in the epithelial stem cells. Dev. Dyn. 239 364–372. PubMed

Takada R., Satomi Y., Kurata T., Ueno N., Norioka S., Kondoh H., et al. (2006). Monounsaturated fatty acid modification of Wnt protein: its role in Wnt secretion. Dev. Cell 11 791–801. 10.1016/j.devcel.2006.10.003 PubMed DOI

Takeshita A., Iwai S., Morita Y., Niki-Yonekawa A., Hamada M., Yura Y. (2014). Wnt5b promotes the cell motility essential for metastasis of oral squamous cell carcinoma through active Cdc42 and RhoA. Int. J. Oncol. 44 59–68. 10.3892/ijo.2013.2172 PubMed DOI

Tang Q., Chen C., Zhang Y., Dai M., Jiang Y., Wang H., et al. (2018). Wnt5a regulates the cell proliferation and adipogenesis via MAPK-independent pathway in early stage of obesity. Cell Biol. Int. 42 63–74. 10.1002/cbin.10862 PubMed DOI

Tao J., Shi L., Huang L., Shi H., Chen H., Wang Y., et al. (2017). EZH2 is involved in silencing of WNT5A during epithelial-mesenchymal transition of colon cancer cell line. J. Cancer Res. Clin. Oncol. 143 2211–2219. 10.1007/s00432-017-2479-2 PubMed DOI PMC

Tao S. C., Yuan T., Zhang Y. L., Yin W. J., Guo S. C., Zhang C. Q. (2017). Exosomes derived from miR-140-5p-overexpressing human synovial mesenchymal stem cells enhance cartilage tissue regeneration and prevent osteoarthritis of the knee in a rat model. Theranostics 7 180–195. 10.7150/thno.17133 PubMed DOI PMC

Taylor B. L., Liu F. F., Sander M. (2013). Nkx6.1 is essential for maintaining the functional state of pancreatic beta cells. Cell Rep. 4 1262–1275. 10.1016/j.celrep.2013.08.010 PubMed DOI PMC

Vaidya H., Rumph C., Katula K. S. (2016). Inactivation of the WNT5A alternative promoter B is associated with DNA methylation and histone modification in osteosarcoma cell lines U2OS and SaOS-2. PLoS One 11:e0151392. 10.1371/journal.pone.0151392 PubMed DOI PMC

van Amerongen R., Nusse R. (2009). Towards an integrated view of Wnt signaling in development. Development 136 3205–3214. 10.1242/dev.033910 PubMed DOI

van Dijk E. M., Menzen M. H., Spanjer A. I., Middag L. D., Brandsma C. A., Gosens R. (2016). Noncanonical WNT-5B signaling induces inflammatory responses in human lung fibroblasts. Am. J. Physiol. Lung Cell. Mol. Physiol. 310 L1166–L1176. PubMed

van Tienen F. H., Laeremans H., van der Kallen C. J., Smeets H. J. (2009). Wnt5b stimulates adipogenesis by activating PPARgamma, and inhibiting the beta-catenin dependent Wnt signaling pathway together with Wnt5a. Biochem. Biophys. Res. Commun. 387 207–211. 10.1016/j.bbrc.2009.07.004 PubMed DOI

Vethe H., Ghila L., Berle M., Hoareau L., Haaland O. A., Scholz H., et al. (2019). The effect of Wnt pathway modulators on human iPSC-derived pancreatic beta cell maturation. Front. Endocrinol. (Lausanne) 10:293. 10.3389/fendo.2019.00293 PubMed DOI PMC

Wang Q., Symes A. J., Kane C. A., Freeman A., Nariculam J., Munson P., et al. (2010). A novel role for Wnt/Ca2+ signaling in actin cytoskeleton remodeling and cell motility in prostate cancer. PLoS One 5:e10456. 10.1371/journal.pone.0010456 PubMed DOI PMC

Wang S. H., Chang J. S., Hsiao J. R., Yen Y. C., Jiang S. S., Liu S. H., et al. (2017). Tumour cell-derived WNT5B modulates in vitro lymphangiogenesis via induction of partial endothelial-mesenchymal transition of lymphatic endothelial cells. Oncogene 36 1503–1515. 10.1038/onc.2016.317 PubMed DOI

Wang X., Zhao X., Yi Z., Ma B., Wang H., Pu Y., et al. (2018). WNT5A promotes migration and invasion of human osteosarcoma cells via SRC/ERK/MMP-14 pathway. Cell Biol. Int. 42 598–607. 10.1002/cbin.10936 PubMed DOI

Wei W., Sun H. H., Li N., Li H. Y., Li X., Li Q., et al. (2014). WNT5A modulates cell cycle progression and contributes to the chemoresistance in pancreatic cancer cells. Hepatobiliary Pancreat. Dis. Int. 13 529–538. 10.1016/s1499-3872(14)60277-0 PubMed DOI

Winter C. G., Wang B., Ballew A., Royou A., Karess R., Axelrod J. D., et al. (2001). Drosophila Rho-associated kinase (Drok) links Frizzled-mediated planar cell polarity signaling to the actin cytoskeleton. Cell 105 81–91. 10.1016/s0092-8674(01)00298-7 PubMed DOI

Witte F., Dokas J., Neuendorf F., Mundlos S., Stricker S. (2009). Comprehensive expression analysis of all Wnt genes and their major secreted antagonists during mouse limb development and cartilage differentiation. Gene Expr. Patterns 9 215–223. 10.1016/j.gep.2008.12.009 PubMed DOI

Wong G. T., Gavin B. J., McMahon A. P. (1994). Differential transformation of mammary epithelial cells by Wnt genes. Mol. Cell. Biol. 14 6278–6286. 10.1128/mcb.14.9.6278 PubMed DOI PMC

Wu B. T., Wen S. H., Hwang S. P., Huang C. J., Kuan Y. S. (2015). Control of Wnt5b secretion by Wntless modulates chondrogenic cell proliferation through fine-tuning fgf3 expression. J. Cell. Sci. 128 2328–2339. 10.1242/jcs.167403 PubMed DOI

Wu M., Li Z., Liang L., Ma P., Cui D., Chen P., et al. (2020). Wnt signaling contributes to withdrawal symptoms from opioid receptor activation induced by morphine exposure or chronic inflammation. Pain 161 532–544. 10.1097/j.pain.0000000000001738 PubMed DOI PMC

Wu X., van Dijk E. M., Ng-Blichfeldt J. P., Bos I. S. T., Ciminieri C., Konigshoff M., et al. (2019). Mesenchymal WNT-5A/5B signaling represses lung alveolar epithelial progenitors. Cells 8:1147. 10.3390/cells8101147 PubMed DOI PMC

Xiao Q., Chen Z., Jin X., Mao R., Chen Z. (2017). The many postures of noncanonical Wnt signaling in development and diseases. Biomed. Pharmacother. 93 359–369. 10.1016/j.biopha.2017.06.061 PubMed DOI

Xu A., Yang H., Gao K., Zhan Z., Song Z., Huang T., et al. (2020). Expression profiles and prognostic significance of WNT family members in glioma via bioinformatic analysis. Biosci. Rep. 40:BSR20194255. PubMed PMC

Xuan F., Yano F., Mori D., Chijimatsu R., Maenohara Y., Nakamoto H., et al. (2019). Wnt/beta-catenin signaling contributes to articular cartilage homeostasis through lubricin induction in the superficial zone. Arthritis Res. Ther. 21:247. PubMed PMC

Yamaguchi T. P., Bradley A., McMahon A. P., Jones S. (1999). A Wnt5a pathway underlies outgrowth of multiple structures in the vertebrate embryo. Development 126 1211–1223. PubMed

Yang L., Perez A. A., Fujie S., Warden C., Li J., Wang Y., et al. (2014). Wnt modulates MCL1 to control cell survival in triple negative breast cancer. BMC Cancer 14:124. 10.1186/1471-2407-14-124 PubMed DOI PMC

Yang Y., Topol L., Lee H., Wu J. (2003). Wnt5a and Wnt5b exhibit distinct activities in coordinating chondrocyte proliferation and differentiation. Development 130 1003–1015. 10.1242/dev.00324 PubMed DOI

Yao C. J., Lv Y., Zhang C. J., Jin J. X., Xu L. H., Jiang J., et al. (2018). MicroRNA-185 inhibits the growth and proliferation of osteoblasts in fracture healing by targeting PTH gene through down-regulating Wnt/beta -catenin axis: in an animal experiment. Biochem. Biophys. Res. Commun. 501 55–63. 10.1016/j.bbrc.2018.04.138 PubMed DOI

Ye Z., Zhang C., Tu T., Sun M., Liu D., Lu D., et al. (2013). Wnt5a uses CD146 as a receptor to regulate cell motility and convergent extension. Nat. Commun. 4:2803. PubMed

Yi H., Nakamura R. E., Mohamed O., Dufort D., Hackam A. S. (2007). Characterization of Wnt signaling during photoreceptor degeneration. Invest. Ophthalmol. Vis. Sci. 48 5733–5741. 10.1167/iovs.07-0097 PubMed DOI PMC

Yin P., Bai Y., Wang Z., Sun Y., Gao J., Na L., et al. (2020). Non-canonical Fzd7 signaling contributes to breast cancer mesenchymal-like stemness involving Col6a1. Cell Commun. Signal. 18:143. PubMed PMC

Yuzugullu H., Benhaj K., Ozturk N., Senturk S., Celik E., Toylu A., et al. (2009). Canonical Wnt signaling is antagonized by noncanonical Wnt5a in hepatocellular carcinoma cells. Mol. Cancer 8:90. 10.1186/1476-4598-8-90 PubMed DOI PMC

Zeng R., Huang J., Zhong M. Z., Li L., Yang G., Liu L., et al. (2016). Multiple roles of WNT5A in breast cancer. Med. Sci. Monit. 22 5058–5067. 10.12659/msm.902022 PubMed DOI PMC

Zhang Q., Fan H., Liu H., Jin J., Zhu S., Zhou L., et al. (2020). WNT5B exerts oncogenic effects and is negatively regulated by miR-5587-3p in lung adenocarcinoma progression. Oncogene 39 1484–1497. 10.1038/s41388-019-1071-4 PubMed DOI

Zhang Y., Lin L., Jin Y., Lin Y., Cao Y., Zheng C. (2016). Overexpression of WNT5B promotes COLO 205 cell migration and invasion through the JNK signaling pathway. Oncol. Rep. 36 23–30. 10.3892/or.2016.4772 PubMed DOI

Zhao C., Yu T., Dou Q., Guo Y., Yang X., Chen Y. (2020). Knockout of TLR4 promotes fracture healing by activating Wnt/beta-catenin signaling pathway. Pathol. Res. Pract. 216:152766. 10.1016/j.prp.2019.152766 PubMed DOI

Zheng X., Fan X., Fu B., Zheng M., Zhang A., Zhong K., et al. (2017). EpCAM inhibition sensitizes chemoresistant leukemia to immune surveillance. Cancer Res. 77 482–493. 10.1158/0008-5472.can-16-0842 PubMed DOI

Zheng Y., Wang C., Zhang H., Shao C., Gao L. H., Li S. S., et al. (2016). Polymorphisms in Wnt signaling pathway genes are associated with peak bone mineral density, lean mass, and fat mass in Chinese male nuclear families. Osteoporos. Int. 27 1805–1815. 10.1007/s00198-015-3457-7 PubMed DOI

Zong X., Wang W., Ozes A., Fang F., Sandusky G. E., Nephew K. P. (2020). EZH2-mediated downregulation of the tumor suppressor DAB2IP maintains ovarian cancer stem cells. Cancer Res. 80 4371–4385. 10.1158/0008-5472.can-20-0458 PubMed DOI PMC

Aberrant neurodevelopment in human iPS cell-derived models of Alexander disease