SLC16A3 drives lung adenocarcinoma progression and gefitinib resistance through coordinated regulation of ferroptosis and lactate metabolism.

ABSTRACT:

Background

Ferroptosis is an iron-dependent form of regulated cell death that plays a critical role in tumor suppression and therapeutic response. However, the metabolic mechanisms that drive ferroptosis resistance in lung adenocarcinoma (LUAD), particularly in the context of EGFR-TKI tolerance, remain unclear.

Methods

We integrated transcriptomic and clinical data from TCGA LUAD cohort and performed survival and enrichment analyses. Functional assays, including proliferation, invasion, ferroptosis indicators, and in vivo xenograft models, were used to evaluate the role of SLC16A3. Lactate rescue, transcription factor prediction (JASPAR), mIHC, and luciferase reporter assays were used to dissect regulatory mechanisms. Pharmacological inhibition of SLC16A3 was used to

SUBMITTER: Cai W 

PROVIDER: S-EPMC12640836 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature