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Gene Review

WNT1  -  wingless-type MMTV integration site family...

Homo sapiens

Synonyms: BMND16, INT1, OI15, Proto-oncogene Int-1 homolog, Proto-oncogene Wnt-1
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Disease relevance of WNT1

  • Expression of WNT1 mRNA was up-regulated in 5 out of 10 cases of primary gastric cancer [1].
  • WNT1 mRNA was relatively highly expressed in OKAJIMA cells (gastric cancer) and BxPC-3 cells (pancreatic cancer) [1].
  • Although WNT1 itself has not been implicated in human breast neoplasms, it has been reported that other WNT genes are sometimes overexpressed in human breast cancer and there is growing evidence that downstream components of the Wnt signaling pathway are activated in a significant proportion of breast tumors [2].
  • For these reasons, data obtained from the study of the WNT-1 pathway could be important in our understanding of the mechanisms of epithelial tumors, in general, and probably also of oral squamous cell carcinoma, in particular [3].
  • Insulin and wnt1 pathways cooperate to induce reserve cell activation in differentiation and myotube hypertrophy [4].

High impact information on WNT1

  • CHK1 heterozygosity modestly enhances the tumorigenesis phenotype of WNT-1 transgenic mice [5].
  • Consistent with the expression of Noggin in dorsomedial dermomyotomal cells that lie adjacent to the dorsal neural tube, we have found that coculture of somites with fibroblasts programmed to secrete Wnt1, which is expressed in dorsal neural tube, can induce somitic Noggin expression [6].
  • Reverse transcriptase-PCR analysis revealed expression of five wnt (wnt1, 5a, 10b, 11, and 13) and three fz (fz2, 5, and 7) isoforms in RA synovial tissues [7].
  • The APC tumor-suppressor protein associates with beta-catenin, a cell adhesion protein that is upregulated by the WNT1 oncogene [8].
  • In contrast, Hras1-mutant Wnt1-induced tumors consistently remained oncogene dependent [9].

Biological context of WNT1


Anatomical context of WNT1

  • When presomitic explants are confronted with cells secreting SHH-N and WNT1 simultaneously, competition to specify the sclerotome and dermomyotome domains within the naive mesoderm can be observed [14].
  • Our finding that Wnts transactivate ErbB1 in addition to stimulating the prototypic beta-catenin/TCF pathway may help to explain why wnt1 is a potent oncogene in the mammary gland [12].
  • Differential expression of transporters for norepinephrine and glutamate in wild type, variant, and WNT1-expressing PC12 cells [15].
  • We show that Wnt1 and Wnt3a signaling from the neural tube inhibit Wnt6 expression in the medial surface ectoderm via dermomyotomal Wnt11 [16].
  • These mice exhibit a profound delay in tumorigenesis that is associated with reduced Wnt1-induced accumulation of mammary progenitor cells [17].

Associations of WNT1 with chemical compounds

  • Expression of WNT1 mRNA was significantly up-regulated by beta-estradiol in MCF-7 cells [1].
  • Finally, we demonstrated that the Wnt1-mediated activation of a GAL4-beta-catenin heterologous transcription system was effectively inhibited by STI-571 [18].
  • Transfer of antimicrobial resistance (ampicillin, streptomycin and sulphonamides), the tem-1 gene and markers (int1, qacEDelta1, sul1) characteristic of class 1 integrons were evident in one MDR isolate (resistant to 4 antimicrobial classes) when conjugation and transformation experiments were performed [19].

Regulatory relationships of WNT1

  • There is a strong correlation between the ability of the WNT-1 gene to induce beta-catenin accumulation and its transforming potential in vivo, suggesting that the WNT-1 gene activates an intracellular signaling pathway that can induce the morphological transformation of cells [3].
  • We further show that SFRP2-expressing cells can reduce the dermomyotome-inducing activity of WNT1 and WNT4, but not that of WNT3a [14].

Other interactions of WNT1

  • Three other genes in the 12q13-15 region (CDK2, WNT1 and WNT10b) were not amplified in any of the tumors [20].
  • A search for mutations in WNT1 in a series of patients with Joubert syndrome did not detect mutations at this locus [21].
  • Together, our results support the model that SHH-N at least in part employs SFRP2 to reduce WNT1/4 activity in the somitic mesoderm [14].
  • Interestingly, Wnt proteins from both the Wnt1 and Wnt5A classes, when fused to the same Frizzled, can synergize with LRP6 to activate signaling and induce secondary axes in Xenopus embryos [22].
  • Immunoprecipitation studies demonstrated physical interactions between human Ror2 and mammalian Wnt1 and Wnt3 [23].

Analytical, diagnostic and therapeutic context of WNT1


  1. Expression and regulation of WNT1 in human cancer: up-regulation of WNT1 by beta-estradiol in MCF-7 cells. Katoh, M. Int. J. Oncol. (2003) [Pubmed]
  2. Wnt signaling in breast cancer: have we come full circle? Brown, A.M. Breast Cancer Res. (2001) [Pubmed]
  3. A possible role for the WNT-1 pathway in oral carcinogenesis. Lo Muzio, L. Crit. Rev. Oral Biol. Med. (2001) [Pubmed]
  4. Insulin and wnt1 pathways cooperate to induce reserve cell activation in differentiation and myotube hypertrophy. Rochat, A., Fernandez, A., Vandromme, M., Molès, J.P., Bouschet, T., Carnac, G., Lamb, N.J. Mol. Biol. Cell (2004) [Pubmed]
  5. Chk1 is an essential kinase that is regulated by Atr and required for the G(2)/M DNA damage checkpoint. Liu, Q., Guntuku, S., Cui, X.S., Matsuoka, S., Cortez, D., Tamai, K., Luo, G., Carattini-Rivera, S., DeMayo, F., Bradley, A., Donehower, L.A., Elledge, S.J. Genes Dev. (2000) [Pubmed]
  6. Regulation of dorsal somitic cell fates: BMPs and Noggin control the timing and pattern of myogenic regulator expression. Reshef, R., Maroto, M., Lassar, A.B. Genes Dev. (1998) [Pubmed]
  7. Expression and function of wingless and frizzled homologs in rheumatoid arthritis. Sen, M., Lauterbach, K., El-Gabalawy, H., Firestein, G.S., Corr, M., Carson, D.A. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  8. Regulation of intracellular beta-catenin levels by the adenomatous polyposis coli (APC) tumor-suppressor protein. Munemitsu, S., Albert, I., Souza, B., Rubinfeld, B., Polakis, P. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  9. Isoform-Specific Ras Activation and Oncogene Dependence during MYC- and Wnt-Induced Mammary Tumorigenesis. Jang, J.W., Boxer, R.B., Chodosh, L.A. Mol. Cell. Biol. (2006) [Pubmed]
  10. WNT10A and WNT6, clustered in human chromosome 2q35 region with head-to-tail manner, are strongly coexpressed in SW480 cells. Kirikoshi, H., Sekihara, H., Katoh, M. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  11. Beta-catenin is essential and sufficient for skeletal myogenesis in P19 cells. Petropoulos, H., Skerjanc, I.S. J. Biol. Chem. (2002) [Pubmed]
  12. Wnt1 and Wnt5a induce cyclin D1 expression through ErbB1 transactivation in HC11 mammary epithelial cells. Civenni, G., Holbro, T., Hynes, N.E. EMBO Rep. (2003) [Pubmed]
  13. Endofin, a FYVE Domain Protein, Interacts with Smad4 and Facilitates Transforming Growth Factor-beta Signaling. Chen, Y.G., Wang, Z., Ma, J., Zhang, L., Lu, Z. J. Biol. Chem. (2007) [Pubmed]
  14. SHH-N upregulates Sfrp2 to mediate its competitive interaction with WNT1 and WNT4 in the somitic mesoderm. Lee, C.S., Buttitta, L.A., May, N.R., Kispert, A., Fan, C.M. Development (2000) [Pubmed]
  15. Differential expression of transporters for norepinephrine and glutamate in wild type, variant, and WNT1-expressing PC12 cells. Ramachandran, B., Houben, K., Rozenberg, Y.Y., Haigh, J.R., Varpetian, A., Howard, B.D. J. Biol. Chem. (1993) [Pubmed]
  16. Regulation of ectodermal Wnt6 expression by the neural tube is transduced by dermomyotomal Wnt11: a mechanism of dermomyotomal lip sustainment. Geetha-Loganathan, P., Nimmagadda, S., Huang, R., Christ, B., Scaal, M. Development (2006) [Pubmed]
  17. The Wnt Signaling Receptor Lrp5 Is Required for Mammary Ductal Stem Cell Activity and Wnt1-induced Tumorigenesis. Lindvall, C., Evans, N.C., Zylstra, C.R., Li, Y., Alexander, C.M., Williams, B.O. J. Biol. Chem. (2006) [Pubmed]
  18. Tyrosine kinase inhibitor STI-571/Gleevec down-regulates the beta-catenin signaling activity. Zhou, L., An, N., Haydon, R.C., Zhou, Q., Cheng, H., Peng, Y., Jiang, W., Luu, H.H., Vanichakarn, P., Szatkowski, J.P., Park, J.Y., Breyer, B., He, T.C. Cancer Lett. (2003) [Pubmed]
  19. Antimicrobial resistance in Irish isolates of verocytotoxigenic Escherichia coli (E. coli)--VTEC. Walsh, C., Duffy, G., O'Mahony, R., Fanning, S., Blair, I.S., McDowell, D.A. Int. J. Food Microbiol. (2006) [Pubmed]
  20. Co-amplification and overexpression of CDK4, SAS and MDM2 occurs frequently in human parosteal osteosarcomas. Wunder, J.S., Eppert, K., Burrow, S.R., Gokgoz, N., Bell, R.S., Andrulis, I.L., Gogkoz, N. Oncogene (1999) [Pubmed]
  21. Clinical nosologic and genetic aspects of Joubert and related syndromes. Chance, P.F., Cavalier, L., Satran, D., Pellegrino, J.E., Koenig, M., Dobyns, W.B. J. Child Neurol. (1999) [Pubmed]
  22. A novel set of Wnt-Frizzled fusion proteins identifies receptor components that activate beta -catenin-dependent signaling. Holmen, S.L., Salic, A., Zylstra, C.R., Kirschner, M.W., Williams, B.O. J. Biol. Chem. (2002) [Pubmed]
  23. The orphan receptor tyrosine kinase Ror2 modulates canonical Wnt signaling in osteoblastic cells. Billiard, J., Way, D.S., Seestaller-Wehr, L.M., Moran, R.A., Mangine, A., Bodine, P.V. Mol. Endocrinol. (2005) [Pubmed]
  24. Chromosome localization of the human oncogene INT1 to 12q13 by in situ hybridization. Arheden, K., Mandahl, N., Strömbeck, B., Isaksson, M., Mitelman, F. Cytogenet. Cell Genet. (1988) [Pubmed]
  25. Analysis of 148 kb of genomic DNA around the wnt1 locus of Fugu rubripes. Gellner, K., Brenner, S. Genome Res. (1999) [Pubmed]
  26. MRP-1/CD9 gene transduction downregulates Wnt signal pathways. Huang, C.L., Liu, D., Masuya, D., Kameyama, K., Nakashima, T., Yokomise, H., Ueno, M., Miyake, M. Oncogene (2004) [Pubmed]
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