| First Author | Wang H | Year | 2013 |
| Journal | J Biol Chem | Volume | 288 |
| Issue | 9 | Pages | 6478-87 |
| PubMed ID | 23306204 | Mgi Jnum | J:196713 |
| Mgi Id | MGI:5489052 | Doi | 10.1074/jbc.M112.419184 |
| Citation | Wang H, et al. (2013) SOX9 regulates low density lipoprotein receptor-related protein 6 (LRP6) and T-cell factor 4 (TCF4) expression and Wnt/beta-catenin activation in breast cancer. J Biol Chem 288(9):6478-87 |
| abstractText | Gene expression profiling has identified breast cancer (BCa) subtypes, including an aggressive basal-like (BL) subtype. The molecular signals underlying the behavior observed in BL-BCa group are largely unknown, although recent results indicate a prevalent increase in Wnt/beta-catenin activity. Our immunohistochemistry study confirmed that SOX9, one of the BL-BCa signature genes, was expressed by most BL-BCa, and its expression correlated with indicators of poor prognosis. Importantly, BCa gene expression profiling strongly associated SOX9 with the expression of Wnt/beta-catenin pathway components, LRP6 and TCF4. In cancer cell lines, SOX9 silencing reduced cell proliferation and invasion, LRP6 and TCF4 transcription, and decreased Wnt/beta-catenin activation. SOX9 expression was also increased by Wnt, indicating that SOX9 is at the center of a positive feedback loop that enhances Wnt/beta-catenin signaling. Consistently, SOX9 overexpression in BCa cell lines and transgenic SOX9 expression in breast epithelium caused increased LRP6 and TCF4 expression and Wnt/beta-catenin activation. These results identify SOX9-mediated Wnt/beta-catenin activation as one of the molecular mechanisms underlying aberrant Wnt/beta-catenin activity in BCa, especially in the BL-BCa subgroup. |
