2. Academic Validation
  3. IL-6 regulates autophagy and chemotherapy resistance by promoting BECN1 phosphorylation

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

  • Nat Commun. 2021 Jun 15;12(1):3651. doi: 10.1038/s41467-021-23923-1.
Fuqing Hu  # 1,  Da Song  # 1,  Yumeng Yan 2,  Changsheng Huang 1,  Chentao Shen 1,  Jingqin Lan 1,  Yaqi Chen 1,  Anyi Liu 1,  Qi Wu 1,  Li Sun 3,  Feng Xu 1,  Fayong Hu 1,  Lisheng Chen 1,  Xuelai Luo 1,  Yongdong Feng 1,  Shengyou Huang 2,  Junbo Hu 4,  Guihua Wang 5
Affiliations

Affiliations

  • 1 GI Cancer Research Institute, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, P. R. China.
  • 2 School of Physics, Huazhong University of Science and Technology, Wuhan, Hubei, P. R. China.
  • 3 Department of Oncology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, P. R. China.
  • 4 GI Cancer Research Institute, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, P. R. China. [email protected].
  • 5 GI Cancer Research Institute, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, P. R. China. [email protected].
  • # Contributed equally.
PMID: 34131122 DOI: 10.1038/s41467-021-23923-1
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.

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