Kaiso at the Crossroads: Understanding the Transition from Inflammatory Bowel Disease to Colorectal Cancer

Individuals diagnosed with inflammatory bowel disease (IBD) experience chronic intestinal inflammation and are at increased risk of developing colitis-associated colorectal cancer (CAC). However, as the mechanisms involved in the IBD-to-CAC transition are not fully elucidated, it is necessary to identify key molecular pathways involved in IBD. Colon biopsies derived from IBD patients, along with primary and metastatic colorectal cancer tumours display elevated expression of the transcription factor Kaiso. Notably, Kaiso over-expressing mice (KaisoTg/+) exhibit altered morphology and chronic intestinal inflammation. RNA-sequencing revealed dysregulated expression of genes linked to immune response in 6 weeks old KaisoTg/+ mice, which were subsequently examined for other factors contributing to inflammation. Immunohistochemical staining of KaisoTg/+ mouse intestines showed unaltered expression of proliferative, apoptotic, and neutrophil protein markers compared to non-transgenic (NonTg) mice. In addition, Gram staining revealed that there was no notable bacterial infiltration into the lamina propria that could explain the inflammatory phenotype. Collectively, our findings implicate Kaiso’s transcriptional activity as the key driver of the inflammatory phenotype, positioning KaisoTg/+ mice as a pivotal model to unravel the IBD-to-CAC transition.