| First Author | Essien BE | Year | 2016 |
| Journal | Cancer Res | Volume | 76 |
| Issue | 23 | Pages | 6877-6887 |
| PubMed ID | 27758879 | Mgi Jnum | J:238011 |
| Mgi Id | MGI:5817853 | Doi | 10.1158/0008-5472.CAN-15-3150 |
| Citation | Essien BE, et al. (2016) Transcription Factor ZBP-89 Drives a Feedforward Loop of beta-Catenin Expression in Colorectal Cancer. Cancer Res 76(23):6877-6887 |
| abstractText | In colorectal cancer, APC-mediated induction of unregulated cell growth involves posttranslational mechanisms that prevent proteasomal degradation of proto-oncogene beta-catenin (CTNNB1) and its eventual translocation to the nucleus. However, about 10% of colorectal tumors also exhibit increased CTNNB1 mRNA. Here, we show in colorectal cancer that increased expression of ZNF148, the gene coding for transcription factor ZBP-89, correlated with reduced patient survival. Tissue arrays showed that ZBP-89 protein was overexpressed in the early stages of colorectal cancer. Conditional deletion of Zfp148 in a mouse model of Apc-mediated intestinal polyps demonstrated that ZBP-89 was required for polyp formation due to induction of Ctnnb1 gene expression. Chromatin immunoprecipitation (ChIP) and EMSA identified a ZBP-89-binding site in the proximal promoter of CTNNB1 Reciprocally, siRNA-mediated reduction of CTNNB1 expression also decreased ZBP-89 protein. ChIP identified TCF DNA binding sites in the ZNF148 promoter through which Wnt signaling regulates ZNF148 gene expression. Suppression of either ZNF148 or CTNNB1 reduced colony formation in WNT-dependent, but not WNT-independent cell lines. Therefore, the increase in intracellular beta-catenin protein initiated by APC mutations is sustained by ZBP-89-mediated feedforward induction of CTNNB1 mRNA. Cancer Res; 76(23); 6877-87. (c)2016 AACR. |
