RSK2 protects human breast cancer cells under endoplasmic reticulum stress through activating AMPKα2-mediated autophagy

Lan Ya Li, Xi Sha Chen, Kuan Song Wang, Yi Di Guan, Xing Cong Ren, Dong Sheng Cao, Xin Yuan Sun, Ao Xue Li, Yong Guang Tao, Yi Zhang, Ming Zhu Yin, Xin Luan Wang, Ming Hua Wu, Jin Ming Yang, Yan Cheng

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


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.

Original languageEnglish
Pages (from-to)6704-6718
Number of pages15
Issue number43
StatePublished - Oct 22 2020

Bibliographical note

Funding Information:
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.

Publisher Copyright:
© 2020, The Author(s), under exclusive licence to Springer Nature Limited.

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research


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