| Note | |
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| Entity | Esophageal cancer |
| Note | It has been shown, in cell cultures of esophageal cancer, that WNT1 results in cytoplasmic accumulation of beta-catenin and activates TCF-dependent transcription (Mizushima et al., 2002). Overexpression of mRNA and protein levels of WNT1 have been positively associated with lymph node metastasis, advanced pathological stage and prognosis of patients with esophageal squamous cell carcinoma (Lv et al., 2012). |
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| Entity | Breast cancer |
| Note | WNT1 has been shown to be markedly elevated in grade I tumors, but declined as tumor grade declined (Wong et al., 2002). Ectopic expression of WNT1, triggers the DNA damage response (DDR) and an ensuing cascade of events resulting in tumorigenic conversion of primary human mammary epithelial cells. WNT1-transformed cells have high telomerase activity and compromised p53 and Rb function, grow as spheres in suspension, and in mice form tumors that closely resemble medullary carcinomas of the breast (Ayyanan et al., 2006). siRNA anti-WNT1 has been shown to induce apoptosis in human breast cancer cell lines (Wieczorek et al., 2008). WNT1 immunoreactivity has been found to be inversely related to histological grade, Ki-67 and p53, positively to , HER-2 and caspase-3 and has been correlated with favorable prognosis of patients with stage II breast cancer (Mylona et al., 2013). |
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| Entity | Basal cell carcinoma of head and neck |
| Note | Overexpression of WNT1 has been positively associated with cytoplasmic beta-catenin (Lo Muzio et al., 2002). |
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| Entity | Sarcoma |
| Note | WNT1 blockade by either monoclonal antibody or siRNA induces cell death in sarcoma cells (Mikami et al., 2005). |
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| Entity | Non-small cell lung cancer (NSCLC) |
| Note | The expression of WNT1 has been positively correlated with c-Myc, cyclin D1, VEGF-A, MMP-7, Ki-67 and intratumoral microvessel density and has been found to negatively influence patients' survival (Huang et al., 2008). WNT1 overexpression has been positively associated with the Ki-67 proliferation index and c-Myc and has been found to exert an unfavorable impact on patients' survival (Nakashima et al., 2008). WNT1 expression has been found to be an independent prognostic factor of poor survival (Xu et al., 2011). |
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| Entity | Gastric cancer |
| Note | The expression levels of WNT1 are positively correlated with tumor size, tumor invasive depth, lymph node metastasis, pTNM stage and negatively influences patients' 5-year survival rate (Zhang and Xue, 2008). |
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| Entity | Neuroblastoma |
| Note | Knockdown of endogenous WNT1 expression results in cell death and inhibits cell growth (Zhang et al., 2009). |
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| Entity | Osteogenesis imperfecta (OI) |
| Note | This disease is a heritable bone fragiility disorder that is usually due to dominant mutations in COL1A1 or COL1A2 and is characterized by reduced bone mass and recurrent fractures. Genetic variations in WNT1 define the bone mineral density quantitative trait locus 16 (BMND16) [MIM:615221]. Variance in bone mineral density influences bone mass, contributes to size determination in the general population, and is a susceptibility factor for osteoporotic fractures. The disease is caused by mutations affecting the gene of WNT1 (Fahiminiya et al., 2013; Faqeih et al., 2013; Laine et al., 2013; Pyott et al., 2013). |
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| Entity | Osteoporosis (OSTEOP) |
| Note | A systemic skeletal disorder characterized by decreased bone mass and deterioration of bone microarchitecture without alteration in the composition of bone. The result is fragile bones and an increased risk of fractures, even after minimal trauma. Osteoporosis is a chronic condition of multifactorial etiology and is usually clinically silent until a fracture occurs. Disease susceptibility is associated with variations affecting the gene of WNT1 (Keupp et al., 2013; Laine et al., 2013). |
| | |
| Increased Wnt signaling triggers oncogenic conversion of human breast epithelial cells by a Notch-dependent mechanism. |
| Ayyanan A, Civenni G, Ciarloni L, Morel C, Mueller N, Lefort K, Mandinova A, Raffoul W, Fiche M, Dotto GP, Brisken C. |
| Proc Natl Acad Sci U S A. 2006 Mar 7;103(10):3799-804. Epub 2006 Feb 24. |
| PMID 16501043 |
| |
| Mutations in WNT1 are a cause of osteogenesis imperfecta. |
| Fahiminiya S, Majewski J, Mort J, Moffatt P, Glorieux FH, Rauch F. |
| J Med Genet. 2013 May;50(5):345-8. doi: 10.1136/jmedgenet-2013-101567. Epub 2013 Feb 23. |
| PMID 23434763 |
| |
| WNT1 mutation with recessive osteogenesis imperfecta and profound neurological phenotype. |
| Faqeih E, Shaheen R, Alkuraya FS. |
| J Med Genet. 2013 Jul;50(7):491-2. doi: 10.1136/jmedgenet-2013-101750. Epub 2013 May 24. |
| PMID 23709755 |
| |
| Wnt1 overexpression promotes tumour progression in non-small cell lung cancer. |
| Huang CL, Liu D, Ishikawa S, Nakashima T, Nakashima N, Yokomise H, Kadota K, Ueno M. |
| Eur J Cancer. 2008 Nov;44(17):2680-8. doi: 10.1016/j.ejca.2008.08.004. Epub 2008 Sep 13. |
| PMID 18790633 |
| |
| Mutations in WNT1 cause different forms of bone fragility. |
| Keupp K, Beleggia F, Kayserili H, Barnes AM, Steiner M, Semler O, Fischer B, Yigit G, Janda CY, Becker J, Breer S, Altunoglu U, Grunhagen J, Krawitz P, Hecht J, Schinke T, Makareeva E, Lausch E, Cankaya T, Caparros-Martin JA, Lapunzina P, Temtamy S, Aglan M, Zabel B, Eysel P, Koerber F, Leikin S, Garcia KC, Netzer C, Schonau E, Ruiz-Perez VL, Mundlos S, Amling M, Kornak U, Marini J, Wollnik B. |
| Am J Hum Genet. 2013 Apr 4;92(4):565-74. doi: 10.1016/j.ajhg.2013.02.010. Epub 2013 Mar 14. |
| PMID 23499309 |
| |
| WNT1 mutations in early-onset osteoporosis and osteogenesis imperfecta. |
| Laine CM, Joeng KS, Campeau PM, Kiviranta R, Tarkkonen K, Grover M, Lu JT, Pekkinen M, Wessman M, Heino TJ, Nieminen-Pihala V, Aronen M, Laine T, Kroger H, Cole WG, Lehesjoki AE, Nevarez L, Krakow D, Curry CJ, Cohn DH, Gibbs RA, Lee BH, Makitie O. |
| N Engl J Med. 2013 May 9;368(19):1809-16. doi: 10.1056/NEJMoa1215458. |
| PMID 23656646 |
| |
| WNT-1 expression in basal cell carcinoma of head and neck. An immunohistochemical and confocal study with regard to the intracellular distribution of beta-catenin. |
| Lo Muzio L, Pannone G, Staibano S, Mignogna MD, Grieco M, Ramires P, Romito AM, De Rosa G, Piattelli A. |
| Anticancer Res. 2002 Mar-Apr;22(2A):565-76. |
| PMID 12014624 |
| |
| Association of beta-catenin, Wnt1, Smad4, Hoxa9, and Bmi-1 with the prognosis of esophageal squamous cell carcinoma. |
| Lv J, Cao XF, Ji L, Zhu B, Wang DD, Tao L, Li SQ. |
| Med Oncol. 2012 Mar;29(1):151-60. doi: 10.1007/s12032-010-9816-5. Epub 2011 Jan 23. |
| PMID 21259057 |
| |
| Efficacy of Wnt-1 monoclonal antibody in sarcoma cells. |
| Mikami I, You L, He B, Xu Z, Batra S, Lee AY, Mazieres J, Reguart N, Uematsu K, Koizumi K, Jablons DM. |
| BMC Cancer. 2005 May 24;5:53. |
| PMID 15913453 |
| |
| Wnt-1 but not epidermal growth factor induces beta-catenin/T-cell factor-dependent transcription in esophageal cancer cells. |
| Mizushima T, Nakagawa H, Kamberov YG, Wilder EL, Klein PS, Rustgi AK. |
| Cancer Res. 2002 Jan 1;62(1):277-82. |
| PMID 11782388 |
| |
| An immunohistochemical evaluation of the proteins Wnt1 and glycogen synthase kinase (GSK)-3b in invasive breast carcinomas. |
| Mylona E, Vamvakaris I, Giannopoulou I, Theohari I, Papadimitriou C, Keramopoulos A, Nakopoulou L. |
| Histopathology. 2013 May;62(6):899-907. doi: 10.1111/his.12095. Epub 2013 Mar 28. |
| PMID 23551536 |
| |
| Wnt1 overexpression associated with tumor proliferation and a poor prognosis in non-small cell lung cancer patients. |
| Nakashima T, Liu D, Nakano J, Ishikawa S, Yokomise H, Ueno M, Kadota K, Huang CL. |
| Oncol Rep. 2008 Jan;19(1):203-9. |
| PMID 18097596 |
| |
| WNT1 mutations in families affected by moderately severe and progressive recessive osteogenesis imperfecta. |
| Pyott SM, Tran TT, Leistritz DF, Pepin MG, Mendelsohn NJ, Temme RT, Fernandez BA, Elsayed SM, Elsobky E, Verma I, Nair S, Turner EH, Smith JD, Jarvik GP, Byers PH. |
| Am J Hum Genet. 2013 Apr 4;92(4):590-7. doi: 10.1016/j.ajhg.2013.02.009. Epub 2013 Mar 14. |
| PMID 23499310 |
| |
| Silencing of Wnt-1 by siRNA induces apoptosis of MCF-7 human breast cancer cells. |
| Wieczorek M, Paczkowska A, Guzenda P, Majorek M, Bednarek AK, Lamparska-Przybysz M. |
| Cancer Biol Ther. 2008 Feb;7(2):268-74. Epub 2007 Nov 14. |
| PMID 18059186 |
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| Expression of frizzled-related protein and Wnt-signalling molecules in invasive human breast tumours. |
| Wong SC, Lo SF, Lee KC, Yam JW, Chan JK, Wendy Hsiao WL. |
| J Pathol. 2002 Feb;196(2):145-53. |
| PMID 11793365 |
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| Aberrant Wnt1/beta-catenin expression is an independent poor prognostic marker of non-small cell lung cancer after surgery. |
| Xu X, Sun PL, Li JZ, Jheon S, Lee CT, Chung JH. |
| J Thorac Oncol. 2011 Apr;6(4):716-24. doi: 10.1097/JTO.0b013e31820c5189. |
| PMID 21336184 |
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| Wnt pathway is involved in advanced gastric carcinoma. |
| Zhang H, Xue Y. |
| Hepatogastroenterology. 2008 May-Jun;55(84):1126-30. |
| PMID 18705344 |
| |
| The effect on cell growth by Wnt1 RNAi in human neuroblastoma SH-SY5Y cell line. |
| Zhang L, Li K, Lv Z, Xiao X, Zheng J. |
| Pediatr Surg Int. 2009 Dec;25(12):1065-71. doi: 10.1007/s00383-009-2481-0. Epub 2009 Sep 16. |
| PMID 19756656 |
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