BRAF^V600E-mutated serrated colorectal neoplasia drives transcriptional activation of cholesterol metabolism.

ABSTRACT: BRAF mutations occur early in serrated colorectal cancers, but their long-term influence on tissue homeostasis is poorly characterized. We investigated the impact of short-term (3 days) and long-term (6 months) expression of Braf^V600E in the intestinal tissue of an inducible mouse model. We show that Braf^V600E perturbs the homeostasis of intestinal epithelial cells, with impaired differentiation of enterocytes emerging after prolonged expression of the oncogene. Moreover, Braf^V600E leads to a persistent transcriptional reprogramming with enrichment of numerous gene signatures indicative of proliferation and tumorigenesis, and signatures suggestive of metabolic rewiring. We focused on the top-ranking cholesterol biosynthesis signature and confirmed its incre

SUBMITTER: Rzasa P 

PROVIDER: S-EPMC10514332 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature