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IL-6 regulates autophagy and chemotherapy resistance by promoting BECN1 phosphorylation

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Listed:
  • Fuqing Hu

    (GI Cancer Research Institute, Tongji Hospital, Huazhong University of Science and Technology)

  • Da Song

    (GI Cancer Research Institute, Tongji Hospital, Huazhong University of Science and Technology)

  • Yumeng Yan

    (School of Physics, Huazhong University of Science and Technology)

  • Changsheng Huang

    (GI Cancer Research Institute, Tongji Hospital, Huazhong University of Science and Technology)

  • Chentao Shen

    (GI Cancer Research Institute, Tongji Hospital, Huazhong University of Science and Technology)

  • Jingqin Lan

    (GI Cancer Research Institute, Tongji Hospital, Huazhong University of Science and Technology)

  • Yaqi Chen

    (GI Cancer Research Institute, Tongji Hospital, Huazhong University of Science and Technology)

  • Anyi Liu

    (GI Cancer Research Institute, Tongji Hospital, Huazhong University of Science and Technology)

  • Qi Wu

    (GI Cancer Research Institute, Tongji Hospital, Huazhong University of Science and Technology)

  • Li Sun

    (Tongji Hospital, Huazhong University of Science and Technology)

  • Feng Xu

    (GI Cancer Research Institute, Tongji Hospital, Huazhong University of Science and Technology)

  • Fayong Hu

    (GI Cancer Research Institute, Tongji Hospital, Huazhong University of Science and Technology)

  • Lisheng Chen

    (GI Cancer Research Institute, Tongji Hospital, Huazhong University of Science and Technology)

  • Xuelai Luo

    (GI Cancer Research Institute, Tongji Hospital, Huazhong University of Science and Technology)

  • Yongdong Feng

    (GI Cancer Research Institute, Tongji Hospital, Huazhong University of Science and Technology)

  • Shengyou Huang

    (School of Physics, Huazhong University of Science and Technology)

  • Junbo Hu

    (GI Cancer Research Institute, Tongji Hospital, Huazhong University of Science and Technology)

  • Guihua Wang

    (GI Cancer Research Institute, Tongji Hospital, Huazhong University of Science and Technology)

Abstract

Extracellular cytokines are enriched in the tumor microenvironment and regulate various important properties of cancers, including autophagy. However, the precise molecular mechanisms underlying the link between autophagy and extracellular cytokines remain to be elucidated. In the present study, we demonstrate that IL-6 activates autophagy through the IL-6/JAK2/BECN1 pathway and promotes chemotherapy resistance in colorectal cancer (CRC). Mechanistically, IL-6 triggers the interaction between JAK2 and BECN1, where JAK2 phosphorylates BECN1 at Y333. We demonstrate that BECN1 Y333 phosphorylation is crucial for BECN1 activation and IL-6-induced autophagy by regulating PI3KC3 complex formation. Furthermore, we investigate BECN1 Y333 phosphorylation as a predictive marker for poor CRC prognosis and chemotherapy resistance. Combination treatment with autophagy inhibitors or pharmacological agents targeting the IL-6/JAK2/BECN1 signaling pathway may represent a potential strategy for CRC cancer therapy.

Suggested Citation

  • Fuqing Hu & Da Song & Yumeng Yan & Changsheng Huang & Chentao Shen & Jingqin Lan & Yaqi Chen & Anyi Liu & Qi Wu & Li Sun & Feng Xu & Fayong Hu & Lisheng Chen & Xuelai Luo & Yongdong Feng & Shengyou Hu, 2021. "IL-6 regulates autophagy and chemotherapy resistance by promoting BECN1 phosphorylation," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-23923-1
    DOI: 10.1038/s41467-021-23923-1
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    Cited by:

    1. Yuki Takakura & Moeka Machida & Natsumi Terada & Yuka Katsumi & Seika Kawamura & Kenta Horie & Maki Miyauchi & Tatsuya Ishikawa & Nobuko Akiyama & Takao Seki & Takahisa Miyao & Mio Hayama & Rin Endo &, 2024. "Mitochondrial protein C15ORF48 is a stress-independent inducer of autophagy that regulates oxidative stress and autoimmunity," Nature Communications, Nature, vol. 15(1), pages 1-19, December.

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