MED16 Promotes Tumour Progression and Tamoxifen Sensitivity by Modulating Autophagy through the mTOR Signalling Pathway in ER-Positive Breast Cancer

作者全名："Li, Han; Li, Kang; Shu, Dan; Shen, Meiying; Tan, Zhaofu; Zhang, Wenjie; Pu, Dongyao; Tan, Wenhao; Tang, Zhenrong; Jin, Aishun; Liu, Shengchun"

作者地址："[Li, Han; Li, Kang; Shu, Dan; Shen, Meiying; Tan, Zhaofu; Zhang, Wenjie; Pu, Dongyao; Tan, Wenhao; Tang, Zhenrong; Liu, Shengchun] Chongqing Med Univ, Dept Breast & Thyroid Surg, Affiliated Hosp 1, Chongqing 400016, Peoples R China; [Jin, Aishun] Chongqing Med Univ, Coll Basic Med, Dept Immunol, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China; [Jin, Aishun] Chongqing Med Univ, Chongqing Key Lab Canc Immunol Translat Med, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China"

通信作者："Liu, SC (通讯作者)，Chongqing Med Univ, Dept Breast & Thyroid Surg, Affiliated Hosp 1, Chongqing 400016, Peoples R China.; Jin, AS (通讯作者)，Chongqing Med Univ, Coll Basic Med, Dept Immunol, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China.; Jin, AS (通讯作者)，Chongqing Med Univ, Chongqing Key Lab Canc Immunol Translat Med, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China."

来源：LIFE-BASEL

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:000875399800001

JCR分区：Q2

影响因子：3.2

年份：2022

卷号：12

期号：10

开始页：　

结束页：　

文献类型：Article

关键词：MED16; breast cancer; oestrogen receptor-positive; mTOR signalling pathway; autophagy

摘要："Recent studies have shown that the mediator complex (MED) plays a vital role in tumorigenesis and development, but the role of MED16 (mediator complex subunit 16) in breast cancer (BC) is not clear. Increasing evidence has shown that the mTOR pathway is important for tumour progression and therapy. In this study, we demonstrated that the mTOR signalling pathway is regulated by the expression level of MED16 in ER+ breast cancer. With the analysis of bioinformatics data and clinical specimens, we revealed an elevated expression of MED16 in luminal subtype tumours. We found that MED16 knockdown significantly inhibited cell proliferation and promoted G1 phase cell cycle arrest in ER+ BC cell lines. Downregulation of MED16 markedly reduced the sensitivity of ER+ BC cells to tamoxifen and increased the stemness and autophagy of ER+ BC cells. Bioinformatic analysis of similar genes to MED16 were mainly enriched in autophagy, endocrine therapy and mTOR signalling pathways, and the inhibition of mTOR-mediated autophagy restored sensitivity to tamoxifen by MED16 downregulation in ER+ BC cells. These results suggest an important role of MED16 in the regulation of tamoxifen sensitivity in ER+ BC cells, crosstalk between the mTOR signalling pathway-induced autophagy, and together, with the exploration of tamoxifen resistance, may indicate a new therapy option for endocrine therapy-resistant patients."

基金机构："National Natural Science Foundation of China [81472658]; Key Research and Development Project of Chongqing's Technology Innovation and Application Development Special Big Health Field [CSTC2021jscx-gksb-N0027]; Chongqing Municipal Natural Science Foundation, China [cstc2018jcyjAX0194]"

基金资助正文："This research was funded by the National Natural Science Foundation of China (Grant nos. 81472658), the Key Research and Development Project of Chongqing's Technology Innovation and Application Development Special Big Health Field (Grant no. CSTC2021jscx-gksb-N0027) and the Chongqing Municipal Natural Science Foundation, China (cstc2018jcyjAX0194)."