Loss of colonic fidelity enables multilineage plasticity and metastasis.

ABSTRACT: Cancer cell plasticity enables the acquisition of new phenotypic features and is implicated as a major driver of metastatic progression^1,2. Metastasis occurs mostly in the absence of additional genetic alterations^3-5, which suggests that epigenetic mechanisms are important⁶. However, they remain poorly defined. Here we identify the chromatin-remodelling enzyme ATRX as a key regulator of colonic lineage fidelity and metastasis in colorectal cancer. Atrx loss promotes tumour invasion and metastasis, concomitant with a loss of colonic epithelial identity and the emergence of highly plastic mesenchymal and squamous-like cell states. Combined analysis of chromatin accessibility and enhancer mapping identified impairment of activity of the colonic lineage-specify

SUBMITTER: Cammareri P 

PROVIDER: S-EPMC12350155 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature