Journal article

Necroptosis is dispensable for the development of inflammation-associated or sporadic colon cancer in mice

Silvia Alvarez-Diaz, Adele Preaudet, Andre L Samson, Paul M Nguyen, Ka Yee Fung, Alexandra L Garnham, Warren S Alexander, Andreas Strasser, Matthias Ernst, Tracy L Putoczki, James M Murphy

Cell Death & Differentiation | SPRINGERNATURE | Published : 2020

Abstract

Chronic inflammation of the large intestine is associated with an increased risk of developing colorectal cancer (CRC), the second most common cause of cancer-related deaths worldwide. Necroptosis has emerged as a form of lytic programmed cell death that, distinct from apoptosis, triggers an inflammatory response. Dysregulation of necroptosis has been linked to multiple chronic inflammatory diseases, including inflammatory bowel disease and cancer. Here, we used murine models of acute colitis, colitis-associated CRC, sporadic CRC, and spontaneous intestinal tumorigenesis to investigate the role of necroptosis in these gastrointestinal pathologies. In the Dextran Sodium Sulfate-induced acute ..

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Grants

Awarded by Cancer Council Victoria


Awarded by National Health and Medical Research Council (NHMRC) of Australia


Awarded by Victorian Cancer Agency Fellowship


Awarded by NHMRC IRIISS


Funding Acknowledgements

We thank Drs Kim Newton and Vishva Dixit (Genentech) for provision of the Ripk3<SUP>-/-</SUP> mouse strain. This project was funded by Cancer Council Victoria (1086419) with additional support from the National Health and Medical Research Council (NHMRC) of Australia (1113577, 1058344 to WSA; 461221, 1116937, 1113133, 1143105 to AS; 1124735, 1124737, 1105754, 1172929 to JMM) and a WEHI Dyson Bequest Centenary Fellowship (TLP), and Victorian Cancer Agency Fellowship (MCRF16009 to TLP). We gratefully acknowledge infrastructure support from the NHMRC IRIISS (9000587) and the Victorian State Government Operational Infrastructure Support Program.