Cytochrome c Oxidase Subunit 5A (COX5A) Enhances Gastric Cancer Progression by Augmenting ATP Synthesis and Activating the PI3K/Akt Pathway.

Gastric cancer (GC) is a lethal malignancy characterised by poor prognosis. In this study, we identify cytochrome c oxidase subunit 5A (COX5A) as a key metabolic driver and prognostic biomarker in GC. COX5A was upregulated in tumours and correlated with poor survival. Mechanistically, COX5A enhanced mitochondrial oxidative phosphorylation to elevate ATP production, activating PI3K/Akt signalling to drive proliferation, migration, and invasion. These effects were reversed by PI3K/Akt inhibitors. JC-1 assays revealed COX5A-mediated mitochondrial membrane potential elevation, indicating amplified bioenergetic output. In vivo, COX5A silencing suppressed xenograft tumour growth. Our results demonstrate COX5A orchestrates metabolic reprogramming and PI3K/Akt-mediated progression in GC, positioning it as both a prognostic indicator and therapeutic target.