Stromal interaction molecule 1/microtubule-associated protein 1A/1B-light chain 3B complex induces metastasis of hepatocellular carcinoma by promoting autophagy

作者全名："Wang, Jingchun; Xie, Qichao; Wu, Lei; Zhou, Yu; Xu, Yanquan; Chen, Yu; Zhang, Jiangang; Ren, Ran; Yang, Shiming; Li, Yongsheng; Zhao, Huakan"

作者地址："[Wang, Jingchun; Yang, Shiming] Army Med Univ, Affiliated Hosp 2, Dept Gastroenterol, Chongqing, Peoples R China; [Xie, Qichao] Chongqing Med Univ, Affiliated Hosp 3, Dept Oncol, Chongqing, Peoples R China; [Wu, Lei; Zhou, Yu; Chen, Yu; Zhang, Jiangang; Ren, Ran; Li, Yongsheng; Zhao, Huakan] Chongqing Univ, Canc Hosp, Dept Med Oncol, Chongqing, Peoples R China; [Xu, Yanquan] Army Med Univ, Affiliated Hosp 2, Clin Med Res Ctr, Chongqing, Peoples R China; [Yang, Shiming] Army Med Univ, Dept Gastroenterol, Affiliated Hosp 2, Chongqing 400037, Peoples R China; [Li, Yongsheng; Zhao, Huakan] Chongqing Univ, Canc Hosp, Dept Med Oncol, Chongqing 400030, Peoples R China"

通信作者："Yang, SM (通讯作者)，Army Med Univ, Dept Gastroenterol, Affiliated Hosp 2, Chongqing 400037, Peoples R China.; Li, YS; Zhao, HK (通讯作者)，Chongqing Univ, Canc Hosp, Dept Med Oncol, Chongqing 400030, Peoples R China."

来源：MEDCOMM

ESI学科分类：　

WOS号：WOS:001159745200001

JCR分区：Q1

影响因子：9.9

年份：2024

卷号：5

期号：2

开始页：　

结束页：　

文献类型：Article

关键词：autophagy; epithelial-mesenchymal transition/EMT; hepatocellular carcinoma/HCC; microtubule-associated protein 1A/1B-light chain 3B/LC3B; stromal interaction molecule 1/STIM1

摘要："Metastasis is the leading cause of death in hepatocellular carcinoma (HCC) patients, and autophagy plays a crucial role in this process by orchestrating epithelial-mesenchymal transition (EMT). Stromal interaction molecule 1 (STIM1), a central regulator of store-operated calcium entry (SOCE) in nonexcitable cells, is involved in the development and spread of HCC. However, the impact of STIM1 on autophagy regulation during HCC metastasis remains unclear. Here, we demonstrate that STIM1 is temporally regulated during autophagy-induced EMT in HCC cells, and knocking out (KO) STIM1 significantly reduces both autophagy and EMT. Interestingly, STIM1 enhances autophagy through both SOCE-dependent and independent pathways. Mechanistically, STIM1 directly interacts with microtubule-associated protein 1A/1B-light chain 3B (LC3B) to form a complex via the sterile-alpha motif (SAM) domain, which promotes autophagosome formation. Furthermore, deletion of the SAM domain of STIM1 abolishes its binding with LC3B, leading to a decrease in autophagy and EMT in HCC cells. These findings unveil a novel mechanism by which the STIM1/LC3B complex mediates autophagy and EMT in HCC cells, highlighting a potential target for preventing HCC metastasis. The role of STIM1 in regulating autophagy during HCC metastasis remains unclear. In this study, the authors demonstrate that STIM1 enhances autophagy flux by directly binding with LC3B, independently of SOCE. Mechanistically, STIM1 interacts with LC3B through the SAM domain, promoting the formation of autophagosomes. These findings suggest a potential therapeutic approach for preventing HCC metastasis. # image"

基金机构："Major International (Regional) Joint Research Program of the National Natural Science Foundation of China; Chongqing Guide Special Projects [cstc2020jxjl130014]; Natural Science Foundation of Chongqing [cstc2019jcyj-msxmX0190]; Founding for National Clinical Key Specialty (Oncology), Chongqing Young Expert Studio; Chongqing Young and Middle-Aged Medical Excellence Team; Chongqing Young and Middle-aged Medical Talents Project; [81920108027]"

基金资助正文："This work was supported by the Major International (Regional) Joint Research Program of the National Natural Science Foundation of China (No. 81920108027 to Y. L.), Performance Incentive for Scientific Research Institutions of Chongqing Guide Special Projects (No. cstc2020jxjl130014 to H. Z.), Natural Science Foundation of Chongqing (No. cstc2019jcyj-msxmX0190, to Q. X.), and Founding for National Clinical Key Specialty (Oncology), Chongqing Young Expert Studio (to Y. L.), Chongqing Young and Middle-Aged Medical Excellence Team (to Y. L.), and Chongqing Young and Middle-aged Medical Talents Project (to H. Z.)."