Brachyury promotes tamoxifen resistance in breast cancer by targeting SIRT1

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• 作者：Kaichun Li^a ; Mingzhen Ying^a ; Dan Feng^a ; Jie Du^b ; Shiyu Chen^b ; Bing Dan^b ; Cuihua Wang^b ; Yajie Wang^a ; ^{shtumor@163.com} (Dr.)
• 关键词：Brachyury ; SIRT1 ; Tamoxifen resistance ; Breast cancer
• 刊名：Biomedicine & Pharmacotherapy
• 出版年：2016
• 出版时间：December 2016
• 年：2016
• 卷：84
• 期：Complete
• 页码：28-33
• 全文大小：1608 K
• 卷排序：84

文摘

Tamoxifen is effective for treating estrogen receptor-alpha (ERα)-positive breast cancers. However, few molecular mediators of tamoxifen resistance have been elucidated. In the present study, we determine the underlying roles of Brachyury in tamoxifen resistance. Loss- and gain-of-function assay are utilized to confirm the oncogenic roles of Brachyury in breast cancer. Compared with the normal MCF10A cells, Brachyury is commonly overexpressed in breast cancer cell lines. Knockdown of Brachyury inhibits tamoxifen resistance, whereas overexpression of Brachyury enhances tamoxifen resistance as demonstrated increased cell viability and reduced cell apoptosis. Mechanistically, we demonstrate for the first time that Brachyury mediates tamoxifen resistance by regulating Sirtuin-1 (SIRT1). Collectively, our data, as a proof of principle, indicate that Brachyury is a candidate marker for predicting the clinical efficacy of tamoxifen and targeting SIRT1 could overcome resistance to tamoxifen in breast cancer cells.