CDK2-mediated site-specific phosphorylation of EZH2 drives and maintains triple-negative breast cancer.

ABSTRACT: Triple-negative breast cancer (TNBC), which lacks estrogen receptor α (ERα), progesterone receptor, and human epidermal growth factor receptor 2 (HER2) expression, is closely related to basal-like breast cancer. Previously, we and others report that cyclin E/cyclin-dependent kinase 2 (CDK2) phosphorylates enhancer of zeste homolog 2 (EZH2) at T416 (pT416-EZH2). Here, we show that transgenic expression of phospho-mimicking EZH2 mutant EZH2^T416D in mammary glands leads to tumors with TNBC phenotype. Coexpression of EZH2^T416D in mammary epithelia of HER2/Neu transgenic mice reprograms HER2-driven luminal tumors into basal-like tumors. Pharmacological inhibition of CDK2 or EZH2 allows re-expression of ERα and converts TNBC to luminal ERα-positive, rendering TNBC cells tar

SUBMITTER: Nie L 

PROVIDER: S-EPMC6841924 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature