Loss of Aryl Hydrocarbon Receptor Promotes Colon Tumorigenesis in Apc^S580/+; Kras^G12D/+ Mice.

ABSTRACT: The mutational genetic landscape of colorectal cancer has been extensively characterized; however, the ability of "cooperation response genes" to modulate the function of cancer "driver" genes remains largely unknown. In this study, we investigate the role of aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, in modulating oncogenic cues in the colon. We show that intestinal epithelial cell-targeted AhR knockout (KO) promotes the expansion and clonogenic capacity of colonic stem/progenitor cells harboring Apc^S580/+; Kras^G12D/+ mutations by upregulating Wnt signaling. The loss of AhR in the gut epithelium increased cell proliferation, reduced mouse survival rate, and promoted cecum and colon tumorigenesis in mice. Mechanistically, the anta

SUBMITTER: Han H 

PROVIDER: S-EPMC8137548 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature