Linking microbiota changes and lipid signalling to tumour risk in models of unfolded protein response-driven colonic tumorigenesis (P11)

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The endoplasmic reticulum unfolded protein response (UPRER) is linked to intestinal inflammation and cancer, yet its causal role in oncogenic tissue transformation remains incompletely understood. We identified the UPRER activating transcription factor 6 (ATF6) as a novel and clinically relevant target of colorectal cancer and colitis-associated cancer. Chronically activated ATF6 signalling in the epithelium induced alterations in lipid metabolism, including the synthesis of long chain fatty acids, and microbiota adaptations in the tumour niche. We now want to mechanistically link lipid and microbiota signalling to tumour initiation, and better understand inflammation in UPR-related tumorigenesis.