CCN6 Suppresses Metaplastic Breast Carcinoma by Antagonizing Wnt/β-Catenin Signaling to Inhibit EZH2-Driven EMT.

ABSTRACT: Metaplastic breast carcinomas (mBrCA) are a highly aggressive subtype of triple-negative breast cancer with histologic evidence of epithelial-to-mesenchymal transition and aberrant differentiation. Inactivation of the tumor suppressor gene cellular communication network factor 6 (CCN6; also known as Wnt1-induced secreted protein 3) is a feature of mBrCAs, and mice with conditional inactivation of Ccn6 in mammary epithelium (Ccn6-KO) develop spindle mBrCAs with epithelial-to-mesenchymal transition. Elucidation of the precise mechanistic details of how CCN6 acts as a tumor suppressor in mBrCA could help identify improved treatment strategies. In this study, we showed that CCN6 interacts with the Wnt receptor FZD8 and coreceptor LRP6 on mBrCA cells to antagonize Wnt-induced activation of β-ca

SUBMITTER: Gonzalez ME 

PROVIDER: S-EPMC11444886 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature