EGFR-TKIs Induced DPP4 Drives Metabolic Reprogramming of Persister Cells in Lung Cancer.

ABSTRACT: Mutations in epidermal growth factor receptor (EGFR) are the key drivers of lung cancer initiation and recurrence. The cancer cells undergo transformation to a reversible drug-tolerant persister (DTP) state prior to the development of resistance against EGFR-tyrosine kinase inhibitors (TKIs). Two DTP lung cancer cells with different proliferative capacities are established and identified dipeptidyl peptidase 4 (DPP4) as a potential therapeutic target. The DTP cells primarily relied on oxidative phosphorylation, which is accompanied by the up-regulation of fatty acid metabolism. Mechanistically, DPP4 facilitates the uptake of fatty acids via carnitine palmitoyl transferase 1a (CPT1A, and enhances fatty acid oxidation. In addition, the DPP4-mitogen-activated protein kinase kinase (MEK)-Nucle

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC12376602 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature