Loss of DOCK2 potentiates Inflammatory Bowel Disease-associated colorectal cancer via immune dysfunction and IFNγ induction of IDO1 expression.

ABSTRACT: Inflammatory Bowel Disease-associated colorectal cancer (IBD-CRC) is a known and serious complication of Inflammatory Bowel Disease (IBD) affecting the colon. However, relatively little is known about the pathogenesis of IBD-associated colorectal cancer in comparison with its sporadic cancer counterpart. Here, we investigated the function of Dock2, a gene mutated in ~10% of IBD-associated colorectal cancers that encodes a guanine nucleotide exchange factor (GEF). Using a genetically engineered mouse model of IBD-CRC, we found that whole body loss of Dock2 increases tumourigenesis via immune dysregulation. Dock2-deficient tumours displayed increased levels of IFNγ-associated genes, including the tryptophan metabolising, immune modulatory enzyme, IDO1, when compared to Dock2-proficient tumou

SUBMITTER: Churchhouse AMD 

PROVIDER: S-EPMC11473400 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature