ATMLP Enhances Radioresistance in Non-Small Cell Lung Cancer through AKT-Mediated Lipid Droplet Accumulation

Area of Science:

• Oncology
• Molecular Biology
• Metabolism

Background:

• Radiotherapy resistance is a major challenge in non-small cell lung cancer (NSCLC) treatment.
• The mitochondrial peptide ATMLP, encoded by lncRNA AFAP1-AS1, is implicated in tumor progression.

Purpose of the Study:

• To investigate the role of ATMLP in NSCLC radioresistance.
• To elucidate the mechanism by which ATMLP influences radiation response.

Main Methods:

• Investigated ATMLP function in NSCLC cells using genetic knockout and overexpression.
• Analyzed the impact of ATMLP on reactive oxygen species (ROS) levels, AKT pathway activation, and lipid droplet (LD) accumulation.
• Utilized AKT pathway inhibition to assess its role in ATMLP-mediated effects.

Main Results:

• ATMLP promotes radioresistance by enhancing lipid droplet accumulation through AKT activation.
• ATMLP reduces radiation-induced ROS, preventing suppression of AKT phosphorylation.
• Genetic knockout of ATMLP sensitizes NSCLC cells to radiation by increasing ROS and impairing AKT signaling.
• AKT pathway inhibition reverses ATMLP-induced radioresistance.

Conclusions:

• ATMLP is a key mediator linking ROS homeostasis and lipid metabolism to radiation response in NSCLC.
• Targeting the ATMLP-AKT axis presents a potential therapeutic strategy to improve radiotherapy efficacy in NSCLC.