Phosphorylation of EZH2 at T416 by CDK2 contributes to the malignancy of triple negative breast cancers.
作者： Celina G. Kleer , Gabriel N. Hortobagyi , Huang Chun Lien , Longfei Huo , Yi Du
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摘要: Triple-negative breast cancer (TNBC), which is closely related to basal-like cancer, a highly aggressive subtype of that initially responds chemotherapy but eventually develops resistance. This presents major clinical challenge as there are currently no effective targeted therapies available due its lack HER2 and estrogen receptor expression. Here, we show cyclin E the enhancer zeste 2 (EZH2) co-expressed in TNBC patients, E/CDK2 phosphorylates EZH2 at T416 (pT416-EZH2) vivo. Phosphorylation enhances ability promote cell migration/invasion, tumorsphere formation, vivo tumor growth. In addition, high pT416-EZH2 correlates with poorer survival patients. These findings suggest pT416 has potential serve therapeutic biomarker for forms provide rationale use CDK2 inhibitors treat TNBC.
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