BRAF^V600E augments WNT signaling in colorectal cancer via aberrant DNA methylation.

ABSTRACT: The BRAF^V600E mutation drives an aggressive subtype of colorectal cancer (CRC). Although WNT signaling activation is a hallmark of CRC, APC mutations are uncommon in BRAF-V600E mutant CRC, and RNF43 mutations are instead suspected to drive WNT pathway activation. Here, we investigated WNT pathway activation in BRAF-V600E mutant CRC using CRISPR-LbCpf1-corrected BRAF (V600E) and RNF43 (P441fs) organoids. BRAF^E600V organoids regained dependency on EGF receptor signaling, and lost tumorigenic potential. Under identical growth conditions, correction of BRAF^V600E, rather than RNF43^P441fs, suppressed WNT target genes and upregulated epithelial differentiation genes and WNT antagonist genes. DNA methylation analysis revealed promoter hyper

SUBMITTER: El Bouazzaoui L 

PROVIDER: S-EPMC12272824 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature