Knockdown of YAP/TAZ sensitizes tamoxifen-resistant MCF7 breast cancer cells

被引:14
作者
Kim, Yu Jin [1 ,2 ]
Jang, Se-Kyeong [1 ]
Hong, Sung-Eun [3 ]
Park, Chan Sub [4 ]
Seong, Min-Ki [4 ]
Kim, Hyun-Ah [4 ]
Park, Ki Soo [2 ]
Kim, Chun-Ho [5 ]
Park, In-Chul [1 ]
Jin, Hyeon-Ok [3 ]
机构
[1] Korea Inst Radiol & Med Sci, Div Fus Radiol Res, 75 Nowon Ro, Seoul 01812, South Korea
[2] Konkuk Univ, Dept Biol Engn, 120 Neungdong Ro, Seoul 05029, South Korea
[3] Korea Inst Radiol & Med Sci, KIRAMS Radiat Biobank, 75 Nowon Ro, Seoul 01812, South Korea
[4] Korea Inst Radiol & Med Sci, Korea Canc Ctr Hosp, Dept Surg, 75 Nowon Ro, Seoul 01812, South Korea
[5] Korea Inst Radiol & Med Sci, Lab Tissue Engn, 75 Nowon Ro, Seoul 01812, South Korea
基金
新加坡国家研究基金会;
关键词
Breast cancer; Estrogen receptor; PSAT1; Tamoxifen resistance; YAP; TAZ; YAP; DOWNSTREAM; PATHWAY;
D O I
10.1016/j.bbrc.2022.02.083
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Although endocrine therapy with tamoxifen has improved survival in breast cancer patients, resistance to this therapy remains one of the major causes of breast cancer mortality. In the present study, we found that the expression level of YAP/TAZ in tamoxifen-resistant MCF7 (MCF7-TR) breast cancer cells was significantly increased compared with that in MCF7 cells. Knockdown of YAP/TAZ with siRNA sensitized MCF7-TR cells to tamoxifen. Furthermore, siRNA targeting PSAT1, a downstream effector of YAP/TAZ, enhanced sensitivity to tamoxifen in MCF7-TR cells. Additionally, mTORC1 activity and survivin expression were significantly decreased during cell death induced by combination treatment with YAP/ TAZ or PSAT1 siRNA and tamoxifen. In conclusion, targeting the YAP/TAZ-PSAT1 axis could sensitize tamoxifen-resistant MCF7 breast cancer cells by modulating the mTORC1-survivin axis.(c) 2022 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
引用
收藏
页码:73 / 78
页数:6
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