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RSK2 protects human breast cancer cells under endoplasmic reticulum stress through activating AMPKα2-mediated autophagy.
Li, Lan-Ya; Chen, Xi-Sha; Wang, Kuan-Song; Guan, Yi-Di; Ren, Xing-Cong; Cao, Dong-Sheng; Sun, Xin-Yuan; Li, Ao-Xue; Tao, Yong-Guang; Zhang, Yi; Yin, Ming-Zhu; Wang, Xin-Luan; Wu, Ming-Hua; Yang, Jin-Ming; Cheng, Yan.
Afiliación
  • Li LY; Department of Pharmacy, The Second Xiangya Hospital, Central South University, 410011, Changsha, China.
  • Chen XS; Xiangya School of Pharmaceutical Sciences, Central South University, 410008, Changsha, China.
  • Wang KS; Department of Pharmacy, The Second Xiangya Hospital, Central South University, 410011, Changsha, China.
  • Guan YD; Department of Pathology, Xiangya hospital and Department of Pathology, School of Basic Medicine, Central South University, 410078, Changsha, China.
  • Ren XC; Department of Pharmacy, The Second Xiangya Hospital, Central South University, 410011, Changsha, China.
  • Cao DS; Department of Cancer Biology and Toxicology, Department of Pharmacology, College of Medicine, Markey Cancer Center, University of Kentucky, Lexington, KY, 40536, USA.
  • Sun XY; Xiangya School of Pharmaceutical Sciences, Central South University, 410008, Changsha, China.
  • Li AX; Department of Pharmacy, The Second Xiangya Hospital, Central South University, 410011, Changsha, China.
  • Tao YG; Xiangya School of Pharmaceutical Sciences, Central South University, 410008, Changsha, China.
  • Zhang Y; Xiangya School of Pharmaceutical Sciences, Central South University, 410008, Changsha, China.
  • Yin MZ; Cancer Research Institute, School of Basic Medicine, and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Central South University, 410078, Changsha, China.
  • Wang XL; Department of Pharmacology, College of Pharmaceutical Sciences, Soochow University, 410008, Suzhou, China.
  • Wu MH; Department of Dermatology, Hunan Engineering Research Center of Skin Health and Disease, Hunan Key Laboratory of Skin Cancer and Psoriasis, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
  • Yang JM; Translational Medicine R&D Center, Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, 518057, Shenzhen, China.
  • Cheng Y; Cancer Research Institute, School of Basic Medicine, and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Central South University, 410078, Changsha, China.
Oncogene ; 39(43): 6704-6718, 2020 10.
Article en En | MEDLINE | ID: mdl-32958832
Autophagy can protect stressed cancer cell by degradation of damaged proteins and organelles. However, the regulatory mechanisms behind this cellular process remain incompletely understood. Here, we demonstrate that RSK2 (p90 ribosomal S6 kinase 2) plays a critical role in ER stress-induced autophagy in breast cancer cells. We demonstrated that the promotive effect of RSK2 on autophagy resulted from directly binding of AMPKα2 in nucleus and phosphorylating it at Thr172 residue. IRE1α, an ER membrane-associated protein mediating unfolded protein response (UPR), is required for transducing the signal for activation of ERK1/2-RSK2 under ER stress. Suppression of autophagy by knockdown of RSK2 enhanced the sensitivity of breast cancer cells to ER stress both in vitro and in vivo. Furthermore, we demonstrated that inhibition of RSK2-mediated autophagy rendered breast cancer cells more sensitive to paclitaxel, a chemotherapeutic agent that induces ER stress-mediated cell death. This study identifies RSK2 as a novel controller of autophagy in tumor cells and suggests that targeting RSK2 can be exploited as an approach to reinforce the efficacy of ER stress-inducing agents against cancer.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Autofagia / Neoplasias de la Mama / Proteínas Quinasas S6 Ribosómicas 90-kDa / Proteínas Quinasas Activadas por AMP / Antineoplásicos Límite: Animals / Female / Humans Idioma: En Revista: Oncogene Asunto de la revista: BIOLOGIA MOLECULAR / NEOPLASIAS Año: 2020 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Autofagia / Neoplasias de la Mama / Proteínas Quinasas S6 Ribosómicas 90-kDa / Proteínas Quinasas Activadas por AMP / Antineoplásicos Límite: Animals / Female / Humans Idioma: En Revista: Oncogene Asunto de la revista: BIOLOGIA MOLECULAR / NEOPLASIAS Año: 2020 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido