| First Author | Ordóñez-Morán P | Year | 2014 |
| Journal | Oncogene | Volume | 33 |
| Issue | 15 | Pages | 1975-85 |
| PubMed ID | 23624922 | Mgi Jnum | J:212597 |
| Mgi Id | MGI:5581806 | Doi | 10.1038/onc.2013.140 |
| Citation | Ordonez-Moran P, et al. (2014) SPROUTY2 is a beta-catenin and FOXO3a target gene indicative of poor prognosis in colon cancer. Oncogene 33(15):1975-85 |
| abstractText | SPROUTY2 (SPRY2) is an intracellular regulator of receptor tyrosine kinase signaling involved in cell growth, differentiation and tumorigenesis. Here, we show that SPRY2 is a target gene of the Wnt/beta-catenin pathway that is abnormally activated in more than 90% of colon carcinomas. In human colon cancer cells, SPRY2 expression is induced by beta-catenin in co-operation with the transcription factor FOXO3a instead of lymphoid enhancer factor/T-cell factor proteins. We found binding of beta-catenin to the SPRY2 promoter at FOXO3a response elements. In vivo, cells marked by nuclear beta-catenin and FOXO3a express SPRY2 in proliferative epithelial tissues, such as intestinal mucosa and epidermis. Consistently, inducible beta-catenin deletion in mice reduced Spry2 expression in the small intestine. Moreover, SPRY2 protein expression correlated with nuclear beta-catenin and FOXO3a colocalization in human colon carcinomas. Importantly, the amount of SPRY2 protein correlated with shorter overall survival of colon cancer patients. Our data reveal SPRY2 as a novel Wnt/beta-catenin and FOXO3a target gene indicative of poor prognosis in colon cancer. |
