Loss of Pkd1 limits susceptibility to colitis and colorectal cancer.

ABSTRACT: Colorectal cancer (CRC) is one of the most common cancers, with an annual incidence of ~135,000 in the US, associated with ~50,000 deaths. Autosomal dominant polycystic kidney disease (ADPKD), associated with mutations disabling the PKD1 gene, affects as many as 1 in 1000. Intriguingly, some studies have suggested that individuals with germline mutations in PKD1 have reduced incidence of CRC, suggesting a genetic modifier function. Using mouse models, we here establish that loss of Pkd1 greatly reduces CRC incidence and tumor growth induced by loss of the tumor suppressor Apc. Growth of Pkd1^-/-;Apc^-/- organoids was reduced relative to Apc^-/- organoids, indicating a cancer cell-intrinsic activity, even though Pkd1 loss enhanced activity of pro-oncogenic sign

SUBMITTER: Nikonova AS 

PROVIDER: S-EPMC10403611 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature