Chia Nan University of Pharmacy & Science Institutional Repository:Item 310902800/29753
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    標題: COL11A1 confers chemoresistance on ovarian cancer cells through the activation of Akt/c/EBPβ pathway and PDK1 stabilization
    作者: Wu, Yi-Hui
    Chang, Tzu-Hao
    Huang, Yu-Fang
    Chen, Chien-Chin
    Chou, Cheng-Yang
    貢獻者: 化粧品應用與管理系
    關鍵字: epithelial ovarian carcinoma
    chemoresistance
    collagen type XI alpha 1
    Akt
    PDK1
    日期: 2015-09
    上傳時間: 2016-04-19 19:06:57 (UTC+8)
    出版者: Impact Journals Llc
    摘要: Chemoresistance to anticancer drugs substantially reduces survival in epithelial ovarian carcinoma (EOC). Here, microarray analysis showed that collagen type XI alpha 1 (COL11A1) is a chemotherapy response-associated gene. Chemoresistant cells expressed higher COL11A1 and c/EBP beta than chemosensitive cells. COL11A1 or c/EBP beta downregulation suppressed chemoresistance, whereas COL11A1 overexpression attenuated sensitivity to cisplatin and paclitaxel. The c/EBP beta binding site in the COL11A1 promoter was identified as the major determinant of cisplatin-and paclitaxel-induced COL11A1 expression. Immunoprecipitation and immunofluorescence showed that in resistant cells, Akt and PDK1 were highly expressed and that anticancer drugs enhanced binding activity between COL11A1 and PDK1 binding and attenuated PDK1 ubiquitination and degradation. Conversely, chemosensitive cells showed decreased activity of COL11A1 binding to PDK1 and increased PDK1 ubiquitination, which were reversed by COL11A1 overexpression. Analysis of 104 EOC patients showed that high COL11A1 mRNA levels are significantly associated with poor chemoresponse and clinical outcome.
    關聯: Oncotarget, v.6 n.27, pp.23748-23763
    顯示於類別:[化妝品應用與管理系(所)] 期刊論文

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