TCF12 regulates exosome release from epirubicin-treated CAFs to promote ER plus breast cancer cell chemoresistance

作者全名："Qiu, Yuxiang; Wang, Xing; Sun, Yan; Du, Yan-e; Yin, Guobing; Luo, Haojun; Wen, Siyang; Lang, Lei; Liu, Manran; Tang, Xi"

作者地址："[Qiu, Yuxiang; Tang, Xi] Chongqing Med Univ, Affiliated Hosp 1, Dept Lab Med, Chongqing 400016, Peoples R China; [Qiu, Yuxiang; Liu, Manran] Chongqing Med Univ, Key Lab Lab Med Diagnost, Chinese Minist Educ, Chongqing 400016, Peoples R China; [Wang, Xing; Yin, Guobing; Luo, Haojun] Chongqing Med Univ, Affiliated Hosp 2, Dept Thyroid & Breast Surg, Chongqing, Peoples R China; [Sun, Yan] Chongqing Med Univ, Basic Med Sch, Dept Cell Biol & Med Genet, Chongqing 400016, Peoples R China; [Du, Yan-e; Wen, Siyang] Chongqing Med Univ, Affiliated Hosp 2, Dept Lab Med, Chongqing 400010, Peoples R China; [Lang, Lei] Chongqing Univ, Chongqing Univ Cent Hosp, Chongqing Emergency Med Ctr, Sch Med, Chongqing 400014, Peoples R China"

通信作者："Tang, X (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Lab Med, Chongqing 400016, Peoples R China."

来源：BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001003309900001

JCR分区：Q1

影响因子：4.2

年份：2023

卷号：1869

期号：6

开始页：　

结束页：　

文献类型：Article

关键词：Breast cancer; Chemoresistance; CAFs; TCF12; Autophagy; Exosome

摘要："Cancer-associated fibroblasts (CAFs) are the predominant stromal cells in the microenvironment and play important roles in tumor progression, including chemoresistance. However, the response of CAFs to chemo-therapeutics and their effects on chemotherapeutic outcomes are largely unknown. In this study, we showed that epirubicin (EPI) treatment triggered ROS which initiated autophagy in CAFs, TCF12 inhibited autophagy flux and further promoted exosome secretion. Inhibition of EPI-induced reactive oxygen species (ROS) production with N-acetyl-L-cysteine (NAC) or suppression of autophagic initiation with short interfering RNA (siRNA) against ATG5 blunted exosome release from CAFs. Furthermore, exosome secreted from EPI-treated CAFs not only prevented ROS accumulation in CAFs but also upregulated the CXCR4 and c-Myc protein levels in recipient ER+ breast cancer cells, thus promoting EPI resistance of tumor cells. Together, the current study provides novel insights into the role of stressed CAFs in promoting tumor chemoresistance and reveal a new function of TCF12 in regulating autophagy impairment and exosome release."

基金机构：National Natural Science Foundation of China [NSFC 81802653]; China Postdoctoral Science Foundation [2022MD723743]; program for Youth Innovation in Future Medicine of Chongqing Medical University [W0068]

基金资助正文："This work was supported by National Natural Science Foundation of China [grant number NSFC 81802653 for Xi Tang] ; China Postdoctoral Science Foundation [grant number 2022MD723743 for Xing Wang] ;The program for Youth Innovation in Future Medicine of Chongqing Medical University, [grant number W0068 for Haojun Luo and Yan Sun] ."