Phosphorylation of EZH2 at T416 by CDK2 contributes to the malignancy of triple negative breast cancers

作者：Yang Cheng Chieh; LaBaff Adam; Wei Yongkun; Nie Lei; Xia Weiya; Huo Longfei; Yamaguchi Hirohito; Hsu Yi Hsin; Hsu Jennifer L; Liu Dongping; Lang Jingyu; Du Yi; Lien Huang Chun; Li Long Yuan; Deng Rong; Chan Li Chuan; Yao Jun; Kleer Celina G; Hortobagyi Gabriel N; Hung Mien Chie^*

来源：American Journal of Translational Research, 2015, 7(6): 1009-U235.

• CDK2
• EZH2
• phosphorylation

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

• 出版日期2015
• 单位中国医科大学