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Disruption of the lipolysis pathway results in stem cell death through a sterile immunity-like pathway in adult Drosophila

  1. Author:
    Aggarwal,Poonam
    Liu, Zilun
    Cheng, Guang Qian
    Singh,Shree Ram
    Shi,Chunmei
    Chen, Ying
    Sun, Ling V
    Shi,Chunmei

  2. Author Address

    The Basic Research Laboratory, Center for Cancer Research, National Cancer Institute at Frederick, National Institutes of Health, Frederick, MD 21702, USA., State Key Laboratory of Genetic Engineering, School of Life Sciences, Institute of Developmental Biology and Molecular Medicine, Institute of Metabolism and Integrative Biology, Human Phenome Institute, Department of Liver Surgery and Transplantation of Liver Cancer Institute at Zhongshan Hospital, Children 39;s Hospital, Fudan University, Shanghai 200438, China., State Key Laboratory of Genetic Engineering, School of Life Sciences, Institute of Developmental Biology and Molecular Medicine, Institute of Metabolism and Integrative Biology, Human Phenome Institute, Department of Liver Surgery and Transplantation of Liver Cancer Institute at Zhongshan Hospital, Children 39;s Hospital, Fudan University, Shanghai 200438, China. Electronic address: lingsun@fudan.edu.cn., State Key Laboratory of Genetic Engineering, School of Life Sciences, Institute of Developmental Biology and Molecular Medicine, Institute of Metabolism and Integrative Biology, Human Phenome Institute, Department of Liver Surgery and Transplantation of Liver Cancer Institute at Zhongshan Hospital, Children 39;s Hospital, Fudan University, Shanghai 200438, China; The Basic Research Laboratory, Center for Cancer Research, National Cancer Institute at Frederick, National Institutes of Health, Frederick, MD 21702, USA. Electronic address: stevenhou@fudan.edu.cn.,
    1. Year: 2022
    2. Date: Jun 21
  2. Journal: Cell Reports
    1. 39
    2. 12
    3. Pages: 110958
  4. Type of Article: Article
  5. Article Number: 110958
  1. Abstract:

    We previously showed that the Arf1-mediated lipolysis pathway sustains stem cells and cancer stem cells (CSCs); its ablation resulted in necrosis of stem cells and CSCs, which further triggers a systemic antitumor immune response. Here we show that knocking down Arf1 in intestinal stem cells (ISCs) causes metabolic stress, which promotes the expression and translocation of ISC-produced damage-associated molecular patterns (DAMPs; Pretaporter [Prtp] and calreticulin [Calr]). DAMPs regulate macroglobulin complement-related (Mcr) expression and secretion. The secreted Mcr influences the expression and localization of enterocyte (EC)-produced Draper (Drpr) and LRP1 receptors (pattern recognition receptors [PRRs]) to activate autophagy in ECs for ATP production. The secreted ATP possibly feeds back to kill ISCs by activating inflammasome-like pyroptosis. We identify an evolutionarily conserved pathway that sustains stem cells and CSCs, and its ablation results in an immunogenic cascade that promotes death of stem cells and CSCs as well as antitumor immunity. Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.

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External Sources

  1. View Full Text
  2. DOI: 10.1016/j.celrep.2022.110958
  3. PMID: 35732115
  4. PII : S2211-1247(22)00740-9

Library Notes

  1. Fiscal Year: FY2021-2022
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