Phosphorylation of EZH2 at T416 by CDK2 contributes to the malignancy of triple negative breast cancers.
Journal
American journal of translational research
Journal Volume
7
Journal Issue
6
Start Page
1009
End Page
1020
ISSN
1943-8141
Date Issued
2015
Author(s)
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
Li, Long-Yuan
Deng, Rong
Chan, Li-Chuan
Yao, Jun
Kleer, Celina G
Hortobagyi, Gabriel N
Hung, Mien-Chie
Abstract
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.
Subjects
CDK2
EZH2
phosphorylation
Type
journal article