Gain of function p53 mutant R273H confers distinct methylation profiles and consequent YAP/TAZ signaling mediated activation of partial or full EMT states to colon tumours.

ABSTRACT:

Background

Mutations in tumour suppressor p53 are frequently implied in aggressive progression and metastasis in colorectal cancer. But the distinct phenotypes exhibited by site-specific mutations of p53 are not well elucidated. Here, we investigate the epigenetic and transcriptional impact of three major p53 hotspot mutations (R175H, R273H and R282W), through DNA methylation changes and single cell transcriptomics.

Results

We observed that the p53 R273H mutation is associated with a partial epithelial-mesenchymal transition (pEMT) and increased metastatic progression. Analysis of DNA methylation patterns revealed a distinct epigenetic landscape in R273H-mutant tumours, with hypomethylated regions correlating with enhanced transcriptional activation of YAP/TAZ target genes t

SUBMITTER: Rani H 

PROVIDER: S-EPMC12822081 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature