SOX9 and TCF transcription factors associate to mediate Wnt/β-catenin target gene activation in colorectal cancer.

ABSTRACT: Activation of the Wnt/β-catenin pathway regulates gene expression by promoting the formation of a β-catenin-T-cell factor (TCF) complex on target enhancers. In addition to TCFs, other transcription factors interact with the Wnt/β-catenin pathway at different levels to produce tissue-specific patterns of Wnt target gene expression. The transcription factor SOX9 potently represses many Wnt target genes by downregulating β-catenin protein levels. Here, we find using colony formation and cell growth assays that SOX9 surprisingly promotes the proliferation of Wnt-driven colorectal cancer (CRC) cells. In contrast to how it indirectly represses Wnt targets, SOX9 directly co-occupies and activates multiple Wnt-responsive enhancers in CRC cells. Our examination of the binding site grammar of these

SUBMITTER: Ramakrishnan AB 

PROVIDER: S-EPMC9771724 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature