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.
Original language | English (US) |
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Pages (from-to) | 1009-1020 |
Number of pages | 12 |
Journal | American Journal of Translational Research |
Volume | 7 |
Issue number | 6 |
State | Published - Feb 25 2015 |
Keywords
- CDK2
- EZH2
- Phosphorylation
ASJC Scopus subject areas
- Molecular Medicine
- Clinical Biochemistry
- Cancer Research