SOX9 suppresses colon cancer via inhibiting epithelial-mesenchymal transition and SOX2 induction.

ABSTRACT: The Wnt/β-catenin pathway regulates expression of the SOX9 gene, which encodes sex-determining region Y-box (SOX) transcription factor 9, a differentiation factor and potential β-catenin regulator. Because APC tumor suppressor defects in approximately 80% of colorectal cancers (CRCs) activate the Wnt/β-catenin pathway, we studied SOX9 inactivation in CRC biology. Compared with effects of Apc inactivation in mouse colon tumors, combined Apc and Sox9 inactivation instigated more invasive tumors with epithelial-mesenchymal transition (EMT) and SOX2 stem cell factor upregulation. In an independent mouse CRC model with combined Apc, Kras, and Trp53 defects, Sox9 inactivation promoted SOX2 induction and distant metastases. About 20% of 171 human CRCs showed loss of SOX9 protein expression, which

SUBMITTER: Feng Y 

PROVIDER: S-EPMC12126244 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature