CHD4 R975H mutant activates tumorigenic pathways and promotes stemness and M2-like macrophage polarization in endometrial cancer.

ABSTRACT: Endometrial cancer (EC), one of the most prevalent carcinomas in females, is associated with increasing mortality. We identified the CHD4 R975H mutation as a high-frequency occurrence in EC patients through a comprehensive survey of EC databases. Computational predictions suggest that this mutation profoundly impacts the structural and functional integrity of CHD4. Functional assays revealed that the CHD4 R975H mutation enhances EC cell invasion, proliferation, and colony formation, promoting a cancer stem cell (CSC)-like phenotype. RNA-seq analysis of cells expressing CHD4 R975H mutant revealed a transcriptomic landscape marked by the activation of several cancer-promoting signaling pathways, including TNF-α signaling via NF-κB, KRAS, P53, mTOR, TGF-β, EGFR, Myc and growth factor signalin

SUBMITTER: Zhang Q 

PROVIDER: S-EPMC11316823 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature