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Monoacylglycerol lipase regulates cannabinoid receptor 2-dependent macrophage activation and cancer progression

Author

Listed:
  • Wei Xiang

    (Third Military Medical University)

  • Rongchen Shi

    (Third Military Medical University)

  • Xia Kang

    (Third Military Medical University)

  • Xuan Zhang

    (Third Military Medical University)

  • Peng Chen

    (PLA 324 Hospital)

  • Lili Zhang

    (Third Military Medical University)

  • Along Hou

    (Third Military Medical University)

  • Rui Wang

    (Third Military Medical University)

  • Yuanyin Zhao

    (Third Military Medical University)

  • Kun Zhao

    (Third Military Medical University)

  • Yingzhe Liu

    (Third Military Medical University)

  • Yue Ma

    (Third Military Medical University)

  • Huan Luo

    (Third Military Medical University)

  • Shenglan Shang

    (Third Military Medical University)

  • Jinyu Zhang

    (Third Military Medical University)

  • Fengtian He

    (Third Military Medical University)

  • Songtao Yu

    (Third Military Medical University)

  • Lixia Gan

    (Third Military Medical University)

  • Chunmeng Shi

    (Third Military Medical University)

  • Yongsheng Li

    (Third Military Medical University)

  • Wei Yang

    (Southern Medical University)

  • Houjie Liang

    (Third Military Medical University)

  • Hongming Miao

    (Third Military Medical University)

Abstract

Metabolic reprogramming greatly contributes to the regulation of macrophage activation. However, the mechanism of lipid accumulation and the corresponding function in tumor-associated macrophages (TAMs) remain unclear. With primary investigation in colon cancer and confirmation in other cancer models, here we determine that deficiency of monoacylglycerol lipase (MGLL) results in lipid overload in TAMs. Functionally, macrophage MGLL inhibits CB2 cannabinoid receptor-dependent tumor progression in inoculated and genetic cancer models. Mechanistically, MGLL deficiency promotes CB2/TLR4-dependent macrophage activation, which further suppresses the function of tumor-associated CD8+ T cells. Treatment with CB2 antagonists delays tumor progression in inoculated and genetic cancer models. Finally, we verify that expression of macrophage MGLL is decreased in cancer tissues and positively correlated with the survival of cancer patients. Taken together, our findings identify MGLL as a switch for CB2/TLR4-dependent macrophage activation and provide potential targets for cancer therapy.

Suggested Citation

  • Wei Xiang & Rongchen Shi & Xia Kang & Xuan Zhang & Peng Chen & Lili Zhang & Along Hou & Rui Wang & Yuanyin Zhao & Kun Zhao & Yingzhe Liu & Yue Ma & Huan Luo & Shenglan Shang & Jinyu Zhang & Fengtian H, 2018. "Monoacylglycerol lipase regulates cannabinoid receptor 2-dependent macrophage activation and cancer progression," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-04999-8
    DOI: 10.1038/s41467-018-04999-8
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    Cited by:

    1. Ping Yang & Hong Qin & Yiyu Li & Anhua Xiao & Enze Zheng & Han Zeng & Chunxiao Su & Xiaoqing Luo & Qiannan Lu & Meng Liao & Lei Zhao & Li Wei & Zac Varghese & John F. Moorhead & Yaxi Chen & Xiong Z. R, 2022. "CD36-mediated metabolic crosstalk between tumor cells and macrophages affects liver metastasis," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    2. Chen Chen & Bongsoo Park & Emeline Ragonnaud & Monica Bodogai & Xin Wang & Le Zong & Jung-Min Lee & Isabel Beerman & Arya Biragyn, 2022. "Cancer co-opts differentiation of B-cell precursors into macrophage-like cells," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    3. Karel Miettinen & Nattawat Leelahakorn & Aldo Almeida & Yong Zhao & Lukas R. Hansen & Iben E. Nikolajsen & Jens B. Andersen & Michael Givskov & Dan Staerk & Søren Bak & Sotirios C. Kampranis, 2022. "A GPCR-based yeast biosensor for biomedical, biotechnological, and point-of-use cannabinoid determination," Nature Communications, Nature, vol. 13(1), pages 1-16, December.

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