NAT10-mediated lipid metabolic reprogramming drives EGFR-TKI resistance in non-small cell lung cancer via ac4C-dependent mRNA stabilization.

ABSTRACT: The development of resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment represents a significant challenge to targeted therapies for lung cancer. To explore the feasibility of epigenetic therapy in overcoming resistance, an epigenetic drug library was screened, identifying Remodelin as a potent enhancer of EGFR-TKI sensitivity in non-small cell lung cancer (NSCLC) cells. We demonstrated that the cytidine acetyltransferase NAT10 was overexpressed in NSCLC tissues and was associated with poor patient prognosis. NAT10 knockdown inhibited proliferation, increased apoptosis, and enhanced sensitivity to EGFR-TKIs both in vitro and in vivo. Mechanistically, NAT10 promoted EGFR-TKI resistance in NSCLC by remodeling fatty acid metabolism. Specifically, NAT

SUBMITTER: Fang S 

PROVIDER: S-EPMC12661735 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature