MAGEA6 Promoted Gastric Cancer Progression by Activating Mitophagy

Melanoma-associated antigen A6 (MAGEA6) is aberrantly expressed in several cancers and exhibits oncogenic activity. This study aimed to investigate the function and underlying mechanisms of MAGEA6 in gastric cancer (GC). The TCGA dataset was utilized in this study to evaluate MAGEA6 expression in GC. Subsequently, the Transwell assay, EDU labeling, and the Cell Counting Kit-8 were employed to assess the effects of MAGEA6 on the migration and proliferation of GC cells. Mitochondrial autophagy and activity examined using mito-Keima staining, transmission electron microscopy, and the JC-1 assay.We found that MAGEA6 was highly expressed in GC patient tissues and cell lines. Overexpression of MAGEA6 enhanced the migratory and proliferative capabilities of GC cells. Additionally, MAGEA6 overexpression promoted mitophagy and prevented mitochondrial collapse. Mechanistically, MAGEA6 activated the PINK1/PRKN pathway by upregulating the protein expression of S100A9, a mechanism closely associated with the pro-cancer phenotype of MAGEA6.The MAGEA6/S100A9/PINK1/PRKN mitophagy pathway is a potential mechanism that promotes GC progression. It may serve as a promising target for GC therapy.