ABSTRACT 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

exploited as an approach to reinforce the efficacy of ER stress-inducing agents against cancer. Access through your institution Buy or subscribe This is a preview of subscription content,

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OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS SMURF1 ATTENUATES ENDOPLASMIC RETICULUM STRESS

BY PROMOTING THE DEGRADATION OF KEAP1 TO ACTIVATE NRF2 ANTIOXIDANT PATHWAY Article Open access 14 June 2023 XAF1 DRIVES APOPTOTIC SWITCH OF ENDOPLASMIC RETICULUM STRESS RESPONSE THROUGH

DESTABILIZATION OF GRP78 AND CHIP Article Open access 28 July 2022 LAMC2 MITIGATES ER STRESS BY ENHANCING ER-MITOCHONDRIA INTERACTION VIA BINDING TO MYH9 AND MYH10 Article Open access 27

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transformation. J Biol Chem. 2011;286:2057–66. CAS  PubMed  Google Scholar  Download references ACKNOWLEDGEMENTS This work was supported by the National Natural Science Foundation of China

under Grant Nos. 81472593 and 81972480; the Postgraduate Research and Innovation Project of Central South University under Grant No. 1053320183910. AUTHOR INFORMATION Author notes * These

authors contributed equally: Lan-Ya Li, Xi-Sha Chen AUTHORS AND AFFILIATIONS * Department of Pharmacy, The Second Xiangya Hospital, Central South University, 410011, Changsha, China Lan-Ya

Li, Xi-Sha Chen, Yi-Di Guan, Xin-Yuan Sun & Yan Cheng * Xiangya School of Pharmaceutical Sciences, Central South University, 410008, Changsha, China Lan-Ya Li, Dong-Sheng Cao, Xin-Yuan

Sun & Ao-Xue Li * Department of Pathology, Xiangya hospital and Department of Pathology, School of Basic Medicine, Central South University, 410078, Changsha, China Kuan-Song Wang *

Department of Cancer Biology and Toxicology, Department of Pharmacology, College of Medicine, Markey Cancer Center, University of Kentucky, Lexington, KY, 40536, USA Xing-Cong Ren & 

Jin-Ming Yang * Cancer Research Institute, School of Basic Medicine, and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Central South University, 410078,

Changsha, China Yong-Guang Tao & Ming-Hua Wu * Department of Pharmacology, College of Pharmaceutical Sciences, Soochow University, 410008, Suzhou, China Yi Zhang * 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 Ming-Zhu Yin * Translational Medicine R&D Center, Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences,

518057, Shenzhen, China Xin-Luan Wang Authors * Lan-Ya Li View author publications You can also search for this author inPubMed Google Scholar * Xi-Sha Chen View author publications You can

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under endoplasmic reticulum stress through activating AMPKα2-mediated autophagy. _Oncogene_ 39, 6704–6718 (2020). https://doi.org/10.1038/s41388-020-01447-0 Download citation * Received: 26

July 2019 * Revised: 14 August 2020 * Accepted: 24 August 2020 * Published: 21 September 2020 * Issue Date: 22 October 2020 * DOI: https://doi.org/10.1038/s41388-020-01447-0 SHARE THIS

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