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

Lan-Ya Li1,2, Xi-Sha Chen1, Kuan-Song Wang3

  • 1Department of Pharmacy, The Second Xiangya Hospital, Central South University, 410011, Changsha, China.

Oncogene
|September 22, 2020
PubMed

Insights

p90 ribosomal S6 kinase 2 (RSK2) promotes autophagy in breast cancer cells under ER stress by phosphorylating AMPKα2. Inhibiting RSK2 enhances cancer cell sensitivity to chemotherapy by blocking this protective autophagy.

Area of Science:

  • Cellular Biology
  • Molecular Oncology
  • Cancer Research

Background:

  • Autophagy protects cancer cells from stress by degrading damaged components.
  • Mechanisms regulating autophagy, particularly under ER stress, are not fully understood.
  • Understanding these mechanisms is crucial for developing novel cancer therapies.

Purpose of the Study:

  • To investigate the role of RSK2 in ER stress-induced autophagy in breast cancer.
  • To elucidate the molecular pathway through which RSK2 regulates autophagy.
  • To evaluate the therapeutic potential of targeting RSK2 in combination with chemotherapy.

Main Methods:

  • Investigated RSK2's role in autophagy using breast cancer cell lines.
  • Utilized techniques like knockdown, Western blotting, and co-immunoprecipitation.
  • Assessed cancer cell sensitivity to ER stress and paclitaxel in vitro and in vivo.

Main Results:

  • RSK2 directly binds and phosphorylates AMPKα2 in the nucleus, promoting autophagy.
  • IRE1α is essential for ER stress-mediated activation of the ERK1/2-RSK2 pathway.
  • Knockdown of RSK2 increases breast cancer cell sensitivity to ER stress and paclitaxel.

Conclusions:

  • RSK2 is a critical regulator of ER stress-induced autophagy in breast cancer.
  • Targeting RSK2 enhances cancer cell vulnerability to ER stress and chemotherapy.
  • RSK2 inhibition represents a potential strategy to improve the efficacy of ER stress-inducing cancer treatments.

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