RRC ID 72305
Author Aggarwal P, Liu Z, Cheng GQ, Singh SR, Shi C, Chen Y, Sun LV, Hou SX.
Title Disruption of the lipolysis pathway results in stem cell death through a sterile immunity-like pathway in adult Drosophila.
Journal Cell Rep
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.
Volume 39(12)
Pages 110958
Published 2022-6-21
DOI 10.1016/j.celrep.2022.110958
PII S2211-1247(22)00740-9
PMID 35732115
PMC PMC9377423
MeSH Adenosine Triphosphate / metabolism Animals Cell Death Drosophila* / metabolism Lipolysis* Neoplastic Stem Cells / metabolism
IF 8.109
Drosophila 1399R-1 DGRC#124478 DGRC#112001