Journal article
Inflammasome adaptor ASC suppresses apoptosis of gastric cancer cells by an IL18-mediated inflammation-independent mechanism
V Deswaerte, P Nguyen, A West, AF Browning, L Yu, SM Ruwanpura, J Balic, T Livis, C Girard, A Preaudet, H Oshima, KY Fung, H Tye, M Najdovska, M Ernst, M Oshima, C Gabay, T Putoczki, BJ Jenkins
Cancer Research | AMER ASSOC CANCER RESEARCH | Published : 2018
Abstract
Inflammasomes are key regulators of innate immunity in chronic inflammatory disorders and autoimmune diseases, but their role in inflammation-associated tumorigenesis remains ill-defined. Here we reveal a protumorigenic role in gastric cancer for the key inflammasome adaptor apoptosis-related speck-like protein containing a CARD (ASC) and its effector cytokine IL18. Genetic ablation of ASC in the gp130F/F spontaneous mouse model of intestinal-type gastric cancer suppressed tumorigenesis by augmenting caspase-8-like apoptosis in the gastric epithelium, independently from effects on myeloid cells and mucosal inflammation. This phenotype was characterized by reduced activation of caspase-1 and ..
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Funding Acknowledgements
We thank R. Smith and P. Bouillet for comments, K. Fitzgerald (University of Massachusetts Medical School, Worcester, MA) for providing Asc<SUP>-/-</SUP> mice, and C. Nold (Hudson Institute of Medical Research, Melbourne, Australia) for providing anakinra. This work was funded by the National Health and Medical Research Council (NHMRC) of Australia (to B. Jenkins), and the Operational Infrastructure Support Program by the Victorian Government of Australia. P. Nguyen, A. Browning, and J. Balic were supported by Australian Postgraduate Awards from the Australian Government, and A. West was supported by an NHMRC Early Career Fellowship. T. Putoczki was supported by a Victorian Cancer Agency Mid-Career Fellowship. B. Jenkins was supported by an NHMRC Senior Medical Research Fellowship.