NNMT promotes acquired EGFR-TKI resistance by forming EGR1 and lactate-mediated double positive feedback loops in non-small cell lung cancer.

ABSTRACT:

Background

Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are remarkably effective for treating EGFR-mutant non-small cell lung cancer (NSCLC). However, patients inevitably develop acquired drug resistance, resulting in recurrence or metastasis. It is important to identify novel effective therapeutic targets to reverse acquired TKI resistance.

Results

Bioinformatics analysis revealed that nicotinamide N-methyltransferase (NNMT) was upregulated in EGFR-TKI resistant cells and tissues via EGR1-mediated transcriptional activation. High NNMT levels were correlated with poor prognosis in EGFR-mutated NSCLC patients, which could promote resistance to EGFR-TKIs in vitro and in vivo. Mechanistically, NNMT catalyzed the conversion of nicotinamide to 1-methyl

SUBMITTER: Dai J 

PROVIDER: S-EPMC11909984 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature