Hsp90α Mediates BMI1 Expression in Breast Cancer Stem/Progenitor Cells through Facilitating Nuclear Translocation of c-Myc and EZH2

doi:10.3390/ijms18091986

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題名:	Hsp90α Mediates BMI1 Expression in Breast Cancer Stem/Progenitor Cells through Facilitating Nuclear Translocation of c-Myc and EZH2
作者:	Yueh-Chun Lee;Wen-Wei Chang;Yi-Ying Chen;Yu-Hung Tsai;Ying-Hsiang Chou;Hsien-Chun Tseng;Hsin-Lin Chen;Chun-Chieh Wu;Ju Chang-Chien;Hsueh-Te Lee;Huei-Fan Yang;Bing-Yen Wang
貢獻者:	醫學影像暨放射科學系暨碩士班
關鍵詞:	Hsp90α, BMI1, breast cancer stem cells, EZH2, c-Myc, nuclear translocation
日期:	2017-09-15
上傳時間:	2020-08-10T13:35:27Z (UTC)
出版者:	Int J Mol Sci.
摘要:	Abstract Heat shock protein 90 (Hsp90) is a molecular chaperone that facilitates the correct folding and functionality of its client protein. Numerous Hsp90-client proteins are involved in cancer development. Thus, Hsp90 inhibitors have potential applications as anti-cancer drugs. We previously discovered that Hsp90α expression increased in breast cancer stem cells (BCSCs), which can initiate tumorigenesis and metastasis and resist treatment. In the present study, we further demonstrated that 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG), an inhibitor of Hsp90, could suppress the self-renewal of BCSCs by downregulating B lymphoma Mo-MLV insertion region 1 homolog (BMI1), a polycomb family member with oncogenic activity in breast cancer. Through immunoprecipitation analysis, we found that BMI1 did not interact with Hsp90α and that the downregulation of BMI1 by 17-DMAG was mediated by the inhibition of c-Myc and enhancement of zeste homolog 2 (EZH2) expression. The transcriptional and BMI1 promoter-binding activities of c-Myc in BCSCs were inhibited by 17-DMAG treatment. The overexpression of EZH2 attenuated the inhibitory effect of 17-DMAG on BMI1 and c-Myc expression. Furthermore, Hsp90α could be co-immunoprecipitated with c-Myc and EZH2 and bind to the BMI1 promoter. Treatment with 17-DMAG decreased the nuclear expression of EZH2 and c-Myc but not that of Hsp90α. In conclusion, our data suggested that Hsp90α could positively regulate the self-renewal of BCSCs by facilitating the nuclear translocation of c-Myc and EZH2 to maintain BMI1 expression.
URI:	https://ir.csmu.edu.tw:8080/ir/handle/310902500/21079
關聯:	Int J Mol Sci. 2017 Sep; 18(9): 1986.
顯示於類別:	[醫學影像暨放射科學系暨碩士班] 期刊論文

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