wnt2 protein


Summary: A proto-oncogene protein and member of the Wnt family of proteins. It is frequently up-regulated in human GASTRIC CANCER and is a tumor marker (BIOMARKERS, TUMOR) of gastric and COLORECTAL CANCER.

Top Publications

  1. Zhang A, Shen C, Ma S, Ke Y, El Idrissi A. Altered expression of Autism-associated genes in the brain of Fragile X mouse model. Biochem Biophys Res Commun. 2009;379:920-3 pubmed publisher
    ..We found major changes in the expression pattern for the three genes examined. FMR1, MECP2, and WNT2 expression were drastically down regulated in the Fragile X mouse brain. ..
  2. Karasawa T, Yokokura H, Kitajewski J, Lombroso P. Frizzled-9 is activated by Wnt-2 and functions in Wnt/beta -catenin signaling. J Biol Chem. 2002;277:37479-86 pubmed
    ..Rfz9 also relocalizes Axin from the cytoplasm to the plasma membrane in the presence of Dvl-1, suggesting that one of the consequences of Dvl-1 relocalization by Rfz9 is to bring Axin to the cell membrane. ..
  3. McCoy P, Shao Y, Wolpert C, Donnelly S, Ashley Koch A, Abel H, et al. No association between the WNT2 gene and autistic disorder. Am J Med Genet. 2002;114:106-9 pubmed
    ..We did not identify any activating mutation in the coding region of the WNT2 gene. Thus, we conclude that activating mutations of the WNT2 gene are not a major contributor to the development of autistic disorder in these data. ..
  4. Goss A, Tian Y, Tsukiyama T, Cohen E, Zhou D, Lu M, et al. Wnt2/2b and beta-catenin signaling are necessary and sufficient to specify lung progenitors in the foregut. Dev Cell. 2009;17:290-8 pubmed publisher
    ..Together, these data reveal that canonical Wnt2/2b signaling is required for the specification of lung endoderm progenitors in the developing foregut...
  5. Kozopas K, Samos C, Nusse R. DWnt-2, a Drosophila Wnt gene required for the development of the male reproductive tract, specifies a sexually dimorphic cell fate. Genes Dev. 1998;12:1155-65 pubmed
  6. Wayman G, Impey S, Marks D, Saneyoshi T, Grant W, Derkach V, et al. Activity-dependent dendritic arborization mediated by CaM-kinase I activation and enhanced CREB-dependent transcription of Wnt-2. Neuron. 2006;50:897-909 pubmed
    ..This novel signaling pathway contributes to dynamic remodeling of the dendritic architecture in response to neuronal activity during development. ..
  7. You L, He B, Xu Z, Uematsu K, Mazieres J, Mikami I, et al. Inhibition of Wnt-2-mediated signaling induces programmed cell death in non-small-cell lung cancer cells. Oncogene. 2004;23:6170-4 pubmed
  8. Okamoto H, Voleti B, Banasr M, Sarhan M, Duric V, Girgenti M, et al. Wnt2 expression and signaling is increased by different classes of antidepressant treatments. Biol Psychiatry. 2010;68:521-7 pubmed publisher
    ..These findings demonstrate that Wnt2 expression and signaling is a common target of antidepressants and that increased Wnt2 is sufficient to produce antidepressant effects. ..
  9. Kozopas K, Nusse R. Direct flight muscles in Drosophila develop from cells with characteristics of founders and depend on DWnt-2 for their correct patterning. Dev Biol. 2002;243:312-25 pubmed
    ..We conclude that DWnt-2 promotes the correct patterning of DFMs through a mechanism that is independent of the attachment site differentiation initiated by stripe. ..

More Information


  1. Holcombe R, Marsh J, Waterman M, Lin F, Milovanovic T, Truong T. Expression of Wnt ligands and Frizzled receptors in colonic mucosa and in colon carcinoma. Mol Pathol. 2002;55:220-6 pubmed
    ..Altered expression of these Wnts and Fz receptors may prove useful as prognostic or diagnostic markers for patients with colon cancer. ..
  2. Wassink T, Piven J, Vieland V, Huang J, Swiderski R, Pietila J, et al. Evidence supporting WNT2 as an autism susceptibility gene. Am J Med Genet. 2001;105:406-13 pubmed
  3. Li J, Nguyen L, Gleason C, Lotspeich L, Spiker D, Risch N, et al. Lack of evidence for an association between WNT2 and RELN polymorphisms and autism. Am J Med Genet B Neuropsychiatr Genet. 2004;126B:51-7 pubmed
    ..Our interpretation of these findings is that it is unlikely that DNA variations in RELN and WNT2 play a significant role in the genetic predisposition to autism. ..
  4. Le Floch N, Rivat C, De Wever O, Bruyneel E, Mareel M, Dale T, et al. The proinvasive activity of Wnt-2 is mediated through a noncanonical Wnt pathway coupled to GSK-3beta and c-Jun/AP-1 signaling. FASEB J. 2005;19:144-6 pubmed
    ..Our data provide a potential clue for our understanding of the action and crosstalk between Wnt activators and other proinvasive pathways, in relation with matrix substrates and proteases in human cancers. ..
  5. Yu M, Ting D, Stott S, Wittner B, Ozsolak F, Paul S, et al. RNA sequencing of pancreatic circulating tumour cells implicates WNT signalling in metastasis. Nature. 2012;487:510-3 pubmed publisher
    ..Thus, molecular analysis of CTCs may identify candidate therapeutic targets to prevent the distal spread of cancer. ..
  6. Sekine K, Ohuchi H, Fujiwara M, Yamasaki M, Yoshizawa T, Sato T, et al. Fgf10 is essential for limb and lung formation. Nat Genet. 1999;21:138-41 pubmed
    ..Thus, we show here that Fgf10 serves as an essential regulator of lung and limb formation. ..
  7. Cho S, Cepko C. Wnt2b/beta-catenin-mediated canonical Wnt signaling determines the peripheral fates of the chick eye. Development. 2006;133:3167-77 pubmed
    ..Because wingless (wg) plays a similar role in the induction of peripheral eye tissues of Drosophila, these findings indicate a possible conservation of the process that patterns the photoreceptive and support structures of the eye. ..
  8. Shimizu H, Julius M, Giarre M, Zheng Z, Brown A, Kitajewski J. Transformation by Wnt family proteins correlates with regulation of beta-catenin. Cell Growth Differ. 1997;8:1349-58 pubmed
    ..These data also imply the existence of receptors that respond to certain Wnt proteins but not to others. ..
  9. Klein D, Demory A, Peyre F, Kroll J, Augustin H, Helfrich W, et al. Wnt2 acts as a cell type-specific, autocrine growth factor in rat hepatic sinusoidal endothelial cells cross-stimulating the VEGF pathway. Hepatology. 2008;47:1018-31 pubmed publisher
    ..Wnt2 siRNA knock-down confirmed Wnt2 specificity of VEGFR-2 regulation in HSECs. Wnt2 is an autocrine growth and differentiation factor specific for HSECs that synergizes with the VEGF signaling pathway to exert its effects. ..
  10. Klein D, Demory A, Peyre F, Kroll J, Géraud C, Ohnesorge N, et al. Wnt2 acts as an angiogenic growth factor for non-sinusoidal endothelial cells and inhibits expression of stanniocalcin-1. Angiogenesis. 2009;12:251-65 pubmed publisher
    ..In conclusion, we provide evidence that Wnt2 acts as an angiogenic factor for non-sinusoidal endothelium in vitro and in vivo whose target genes undergo complex regulation by the tissue microenvironment. ..
  11. Bellusci S, Henderson R, Winnier G, Oikawa T, Hogan B. Evidence from normal expression and targeted misexpression that bone morphogenetic protein (Bmp-4) plays a role in mouse embryonic lung morphogenesis. Development. 1996;122:1693-702 pubmed
    ..A model is proposed for the role of BMP4 and other signalling molecules in embryonic lung morphogenesis. ..
  12. Ferreira J, Choufani S, Grafodatskaya D, Butcher D, Zhao C, Chitayat D, et al. WNT2 promoter methylation in human placenta is associated with low birthweight percentile in the neonate. Epigenetics. 2011;6:440-9 pubmed
    ..Note: All of the array data in the manuscript can be accessed from the Gene Expression Omnibus (GEO) NCBI database under GEO accession number GSE22326. ..
  13. Spiegelman V, Tang W, Katoh M, Slaga T, Fuchs S. Inhibition of HOS expression and activities by Wnt pathway. Oncogene. 2002;21:856-60 pubmed
    ..These results indicate that expression and activities of HOS are negatively regulated by Wnt/beta-catenin pathway. ..
  14. Xiao X, Zhao Y, Jin R, Chen J, Wang X, Baccarelli A, et al. Fetal growth restriction and methylation of growth-related genes in the placenta. Epigenomics. 2016;8:33-42 pubmed publisher
    ..Our findings demonstrated that placental DNA methylation levels of IGF2, AHRR, HSD11B2 and WNT2 were associated with measures of fetal growth. ..
  15. Kikuchi A. Modulation of Wnt signaling by Axin and Axil. Cytokine Growth Factor Rev. 1999;10:255-65 pubmed
    ..Axil has similar functions to Axin. Thus, Axin and Axil act as scaffold proteins in the Wnt signaling pathway, thereby modulating the Wnt-dependent cellular functions. ..
  16. Zakin L, Mazan S, Maury M, Martin N, Guenet J, Brulet P. Structure and expression of Wnt13, a novel mouse Wnt2 related gene. Mech Dev. 1998;73:107-16 pubmed
    ..These data suggest that Wnt13 function might partially overlap with those of other Wnt genes in the cell signaling mechanisms controlling mesoderm specification during gastrulation and some aspects of brain, heart and lung formation. ..
  17. Tsukamoto H, Lin M, Ohata M, Giulivi C, French S, Brittenham G. Iron primes hepatic macrophages for NF-kappaB activation in alcoholic liver injury. Am J Physiol. 1999;277:G1240-50 pubmed
    ..These results support the pivotal role of heme-derived iron in priming HM for NF-kappaB activation and expression of proinflammatory genes in alcoholic liver injury. ..
  18. Grove E, Tole S, Limon J, Yip L, Ragsdale C. The hem of the embryonic cerebral cortex is defined by the expression of multiple Wnt genes and is compromised in Gli3-deficient mice. Development. 1998;125:2315-25 pubmed
  19. Witte F, Dokas J, Neuendorf F, Mundlos S, Stricker S. Comprehensive expression analysis of all Wnt genes and their major secreted antagonists during mouse limb development and cartilage differentiation. Gene Expr Patterns. 2009;9:215-23 pubmed publisher
    ..We provide a full expression pattern for Wif1 in limb development, for which no limb expression had been documented so far. ..
  20. Liu Z, Li Y, Kong Q, Zhan C, Wang Q, Chen X, et al. Immunohistochemical profiling of Wnt, NF-kappaB, Stat3 and Notch signaling in human epidermal tumors. J Dermatol Sci. 2008;52:133-6 pubmed publisher
  21. Dale T, Weber Hall S, Smith K, Huguet E, Jayatilake H, Gusterson B, et al. Compartment switching of WNT-2 expression in human breast tumors. Cancer Res. 1996;56:4320-3 pubmed
    ..The high level of WNT-2 expression in tumor epithelium suggests that tumorigenesis may involve the ectopic expression of WNT-2 and the creation of an autocrine Wnt signaling loop. ..
  22. Willert K, Logan C, Arora A, Fish M, Nusse R. A Drosophila Axin homolog, Daxin, inhibits Wnt signaling. Development. 1999;126:4165-73 pubmed
    ..The loss-of-function and overexpression phenotypes show that Daxin, like its mammalian counterpart, acts as a negative regulator of wg/Wnt signaling. ..
  23. Gattelli A, Cirio M, Quaglino A, Schere Levy C, Martinez N, Binaghi M, et al. Progression of pregnancy-dependent mouse mammary tumors after long dormancy periods. Involvement of Wnt pathway activation. Cancer Res. 2004;64:5193-9 pubmed
    ..Therefore, our results indicate that during hormone-dependent tumor dormancy, relevant changes in cell population occur, allowing rapid progression after changes in the animal internal milieu. ..
  24. Tulac S, Nayak N, Kao L, Van Waes M, Huang J, Lobo S, et al. Identification, characterization, and regulation of the canonical Wnt signaling pathway in human endometrium. J Clin Endocrinol Metab. 2003;88:3860-6 pubmed
    ..Also, they underscore the likely importance of this family during endometrial development, differentiation and implantation. ..
  25. Park J, Kuehn H, Kim S, Chung K, Choi H, Kim M, et al. Downregulation of Wnt-mediated ROS generation is causally implicated in leprechaunism. Mol Cells. 2010;29:63-9 pubmed publisher
    ..These data show a crosstalk between Wnt and ROS pathways which in turn provides new mechanistic insights at the molecular level into the pathogenesis of leprechaunism. ..
  26. Alexandrovich A, Arno M, Patient R, Shah A, Pizzey J, Brewer A. Wnt2 is a direct downstream target of GATA6 during early cardiogenesis. Mech Dev. 2006;123:297-311 pubmed
  27. Negishi T, Nagai Y, Asaoka Y, Ohno M, Namae M, Mitani H, et al. Retinoic acid signaling positively regulates liver specification by inducing wnt2bb gene expression in medaka. Hepatology. 2010;51:1037-45 pubmed publisher
    ..These results suggest that a common molecular mechanism may underlie liver and pectoral fin specification during piscine embryogenesis. ..
  28. Bayle J, Fitch J, Jacobsen K, Kumar R, Lafyatis R, Lemaire R. Increased expression of Wnt2 and SFRP4 in Tsk mouse skin: role of Wnt signaling in altered dermal fibrillin deposition and systemic sclerosis. J Invest Dermatol. 2008;128:871-81 pubmed
    ..Lesional skin from SSc patients also showed large increases in SFRP4 mRNA and protein levels in the deep dermis compared to healthy skin, suggesting that the Wnt pathway might regulate skin fibrosis in SSc. ..
  29. Li Y, Zhang H, Choi S, Litingtung Y, Chiang C. Sonic hedgehog signaling regulates Gli3 processing, mesenchymal proliferation, and differentiation during mouse lung organogenesis. Dev Biol. 2004;270:214-31 pubmed
    ..Our findings shed light on the role of Shh signaling on Gli3 processing in lung growth and differentiation by regulating several critical genes. ..
  30. Finnson K, Kontogiannea M, Li X, Farookhi R. Characterization of Wnt2 overexpression in a rat granulosa cell line (DC3): effects on CTNNB1 activation. Biol Reprod. 2012;87:12, 1-8 pubmed publisher
  31. Katoh M. Expression and regulation of WNT1 in human cancer: up-regulation of WNT1 by beta-estradiol in MCF-7 cells. Int J Oncol. 2003;22:209-12 pubmed
    ..WNT1 was found to be one of estrogen target genes in human MCF-7 cells, which in part explains Wnt1-induced mammary carcinogenesis in ERalpha knockout mice. ..
  32. Kim H, Park J, Kim S, Kang S, Kim J, Park H, et al. No association between polymorphisms of WNT2 and schizophrenia in a Korean population. BMC Med Genet. 2010;11:78 pubmed publisher
    ..The present study does not support a major role for WNT2 in schizophrenia. This could be due to the size of the population. Therefore, additional studies would be needed to definitively rule out the gene's minor effects. ..
  33. Wang H, Gillio Meina C, Chen S, Gong X, Li T, Bai D, et al. The canonical WNT2 pathway and FSH interact to regulate gap junction assembly in mouse granulosa cells. Biol Reprod. 2013;89:39 pubmed publisher
    ..We propose that the WNT2/CTNNB1 pathway regulates CX43 expression and GJIC in granulosa cells by modulating CTNNB1 stability and localization in adherens junctions, and that this is essential for FSH stimulation of GJIC. ..
  34. Cheng X, Wang Z, Chen X, Sun Y, Kong Q, Liu J, et al. Frequent loss of membranous E-cadherin in gastric cancers: A cross-talk with Wnt in determining the fate of beta-catenin. Clin Exp Metastasis. 2005;22:85-93 pubmed
    ..Altered beta-catenin distribution may result from the imbalance of E-cadherin production and Wnt expression, which confers on gastric cancer cells more aggressive behaviors. ..
  35. Han J, Zhang K, Chen X, Jiang H, Kong Q, Sun Y, et al. Expression of seven gastric cancer-associated genes and its relevance for Wnt, NF-kappaB and Stat3 signaling. APMIS. 2007;115:1331-43 pubmed publisher
  36. Cai Y, Zhu S, Yang W, Pan M, Wang C, Wu W. Downregulation of ?-catenin blocks fibrosis via Wnt2 signaling in human keloid fibroblasts. Tumour Biol. 2017;39:1010428317707423 pubmed publisher
  37. Hiester B, Galati D, Salinas P, Jones K. Neurotrophin and Wnt signaling cooperatively regulate dendritic spine formation. Mol Cell Neurosci. 2013;56:115-27 pubmed publisher
    ..Together, these data suggest that BDNF and Wnt signaling cooperatively regulate dendritic spine formation. ..
  38. Bafico A, Gazit A, Pramila T, Finch P, Yaniv A, Aaronson S. Interaction of frizzled related protein (FRP) with Wnt ligands and the frizzled receptor suggests alternative mechanisms for FRP inhibition of Wnt signaling. J Biol Chem. 1999;274:16180-7 pubmed
    ..All of these findings are consistent with a model by which FRP inhibits Wnt signaling through interactions with Wnt and/or formation of nonfunctional complexes with the frizzled receptor. ..
  39. Casta on B, Stapp A, Gifford C, Spicer L, Hallford D, Hernandez Gifford J. Follicle-stimulating hormone regulation of estradiol production: possible involvement of WNT2 and ?-catenin in bovine granulosa cells. J Anim Sci. 2012;90:3789-97 pubmed publisher
    ..Future studies are necessary to determine if FSH directly regulates CTNNB1 through modulation of AKT or indirectly by up regulating WNT2, which subsequently activates the canonical WNT pathway...
  40. Takayasu H, Murphy P, Sato H, Doi T, Puri P. Embryonic Wnt gene expression in the nitrofen-induced hypoplastic lung using 3-dimensional imaging. J Pediatr Surg. 2010;45:2129-35 pubmed publisher
    ..Optical projection tomography is potentially a useful approach to visualize both gene expression and morphology during very early stages of lung development. ..
  41. Wang H, Li T, Kidder G. WNT2 regulates DNA synthesis in mouse granulosa cells through beta-catenin. Biol Reprod. 2010;82:865-75 pubmed publisher
    ..Taken together, the data indicate that WNT2 regulates beta-catenin localization in granulosa cells, and WNT2/beta-catenin signaling contributes to regulating their proliferation. ..
  42. Chan A, Hilkens J, Kroezen V, Mitchell P, Scambler P, Wainwright B, et al. Molecular cloning and localization to chromosome 6 of mouse INT1L1 gene. Somat Cell Mol Genet. 1989;15:555-62 pubmed
    ..In addition, we demonstrate that the mouse INT1L1 and MET genes are coamplified in lines of spontaneously transformed mouse NIH3T3 cells, indicating that these genes may remain closely linked within the mouse genome. ..
  43. Basu M, Roy S. Wnt/?-catenin pathway is regulated by PITX2 homeodomain protein and thus contributes to the proliferation of human ovarian adenocarcinoma cell, SKOV-3. J Biol Chem. 2013;288:4355-67 pubmed publisher
    ..Our findings will help to understand the molecular mechanism of proliferation in ovarian cancer cells. ..
  44. Satterfield M, Song G, Hayashi K, Bazer F, Spencer T. Progesterone regulation of the endometrial WNT system in the ovine uterus. Reprod Fertil Dev. 2008;20:935-46 pubmed
  45. Cayuso J, Marti E. Morphogens in motion: growth control of the neural tube. J Neurobiol. 2005;64:376-87 pubmed
    ..In this review we will summarize the experimental data that support the idea that classical morphogens can be reused to regulate proliferation of neural precursors. ..
  46. Watanabe O, Imamura H, Shimizu T, Kinoshita J, Okabe T, Hirano A, et al. Expression of twist and wnt in human breast cancer. Anticancer Res. 2004;24:3851-6 pubmed
    ..2% (12/23) of the cancer lesions and 34.8% (8/23) of the normal breast tissues. Twist and Wnt-2 are highly expressed in breast cancer tissue, suggesting that both molecules could play important roles in mammary carcinogenesis. ..
  47. Katoh M. Differential regulation of WNT2 and WNT2B expression in human cancer. Int J Mol Med. 2001;8:657-60 pubmed
    ..Up-regulation of WNT2 mRNA by estrogen might play a key role in some cases of human breast cancer through activation of the beta-catenin - TCF signaling pathway. ..
  48. Lin Y, Zhang S, Rehn M, Itäranta P, Tuukkanen J, Heljasvaara R, et al. Induced repatterning of type XVIII collagen expression in ureter bud from kidney to lung type: association with sonic hedgehog and ectopic surfactant protein C. Development. 2001;128:1573-85 pubmed
    ..Our data suggest that differential organ morphogenesis is regulated by an intra-organ patterning process that involves coordination between inductive signals and matrix molecules, such as type XVIII collagen. ..
  49. Alvania R, Chen X, Ginty D. Calcium signals control Wnt-dependent dendrite growth. Neuron. 2006;50:813-5 pubmed
    ..describes a novel calcium-dependent signaling cascade linking neuronal activity and calcium influx to expression of Wnt-2, a member of a family of proteins that controls elaboration of dendrites. ..
  50. Carmona F, Azuara D, Berenguer Llergo A, Fernandez A, Biondo S, De Oca J, et al. DNA methylation biomarkers for noninvasive diagnosis of colorectal cancer. Cancer Prev Res (Phila). 2013;6:656-65 pubmed publisher
    ..This novel panel of specific methylation markers can be useful for early diagnosis of CRC using stool DNA and may help in the follow-up of high-risk patients with IBD. ..
  51. Alexander M, Kawahara G, Motohashi N, Casar J, Eisenberg I, Myers J, et al. MicroRNA-199a is induced in dystrophic muscle and affects WNT signaling, cell proliferation, and myogenic differentiation. Cell Death Differ. 2013;20:1194-208 pubmed publisher
    ..Together, these studies identify miR-199a-5p as a potential regulator of myogenesis through suppression of WNT-signaling factors that act to balance myogenic cell proliferation and differentiation...
  52. Monkley S, Delaney S, Pennisi D, Christiansen J, Wainwright B. Targeted disruption of the Wnt2 gene results in placentation defects. Development. 1996;122:3343-53 pubmed
    ..These results suggest that Wnt2 is required for the proper vascularisation of the mouse placenta and the placental defects in Wnt2-deficient mice result in a reduction in birthweight and perinatal lethality. ..
  53. Hu J, Connor J. Demonstration and characterization of the iron regulatory protein in human brain. J Neurochem. 1996;67:838-44 pubmed
    ..This latter observation suggests the brain IRP undergoes posttranslational modification, the result of which may influence the stability of the IRE/IRP complex. ..