https://scholars.lib.ntu.edu.tw/handle/123456789/470174
標題: | Phosphorylation of ezh2 at t416 by cdk2 contributes to the malignancy of triple negative breast cancers | 作者: | Yang C.-C. Labaff A. Wei Y. Nie L. Xia W. Huo L. Yamaguchi H. Hsu Y.-H. Hsu J.L. Liu D. Lang J. Du Y. HUANG-CHUN LIEN Li L.-Y. Deng R. Chan L.-C. Yao J. Kleer C.G. Hortobagyi G.N. Hung M.-C. |
關鍵字: | CDK2; EZH2; Phosphorylation | 公開日期: | 2015 | 出版社: | E-Century Publishing Corporation | 卷: | 7 | 期: | 6 | 起(迄)頁: | 1009-1020 | 來源出版物: | American Journal of Translational Research | 摘要: | 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. ? 2015 E-Century Publishing Corporation. All rights reserved. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84939503541&partnerID=40&md5=d73f4c30cd6b04020f0b6c9815b4ec41 https://scholars.lib.ntu.edu.tw/handle/123456789/470174 |
ISSN: | 1943-8141 | SDG/關鍵字: | actin; cyclin dependent kinase 2; cyclin E; methionine; n [5 (5 tert butyl 2 oxazolylmethylthio) 2 thiazolyl] isonipecotamide; nucleophosmin; phospho nucleophosmin; roscovitine; transcription factor EZH2; tubulin; unclassified drug; animal experiment; animal model; animal tissue; Article; autoradiography; carcinogenesis; cell growth; cell invasion; cell migration; controlled study; female; human; human cell; IC50; immunoblotting; immunohistochemistry; immunoprecipitation; mouse; MTT assay; nonhuman; protein phosphorylation; triple negative breast cancer; tumor growth; tumor sphere formation assay |
顯示於: | 病理學科所 |
在 IR 系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。