Phosphorylation regulates EZH2 neoplastic functions in triple-negative breast cancer

An abstract of the study of Anwar et al. about phosphorylation regulates EZH2 neoplastic functions in triple-negative breast cancer is presented. Among other things triple negative (estrogen receptor, progesterone receptor HER2-neu negative) breast cancers (TNBC) comprise 15% of all breast cancers but are responsible for a disproportionately high number of deaths. Overexpression of the histone methyltransferase EZH2 (Enhancer of Zeste Homolog 2) is an independent prognostic biomarker significantly associated with poorly-differentiated TNBCS and poor patient outcome. p38-mediated phosphorylation of EZH2 at T367 contributes to the migratory and invasive properties of TNBC in vitro. Phosphorylation at T367 was also associated with reduced time to metastasis in vivo. Mechanistically, phosphorylation by p38 does not affect binding to other PRC2 members but may affect EZH2 catalytic activity. In clinical specimens, pEZH2 was upregulated in metastases of breast cancer when compared to matched primary tumors from the same patient. p38-mediated phosphorylatiori of EZH2 at 1367 contributes to malignancy of triple-negative breast cancers.