EYA3 promotes the tumorigenesis of gastric cancer through activation of the mTORC1 signaling pathway and inhibition of autophagy.

Gastric cancer (GC) is a leading cause of cancer-related mortality, with a high rate of postoperative recurrence and poor long-term survival. The Eyes Absent (EYA) protein family plays a significant role in cancer progression, with EYA3 being implicated in promoting GC cell proliferation and tumor growth. Utilizing the DepMap database, we identified EYA3 as a gene of interest in GC. We analyzed EYA3 expression in GC tissues and cell lines, performed in vitro assays to assess its role in cell proliferation, and conducted gene set enrichment analysis to explore its relationship with autophagy and the mTORC1 signaling pathway. In vivo, we used a xenograft tumor model to examine the effects of EYA3 expression on tumor progression. EYA3 was consistently upregulated in GC tissues, and its high expression correlated with a decrease in patient survival rates. Silencing EYA3 in GC cell lines resulted in reduced cell proliferation. Inhibition of autophagy and activation of the mTORC1 signaling pathway were observed as mechanisms by which EYA3 may promote GC cell growth. In vivo experiments supported the in vitro findings, showing slower tumor growth with reduced EYA3 expression. Our study confirms the upregulation of EYA3 in GC and its association with poor prognosis. EYA3 promotes GC cell proliferation and tumor growth by activating the mTORC1 signaling pathway and inhibiting autophagy. These findings highlight the potential of EYA3 as a therapeutic target for GC, providing a foundation for future research and treatment strategies. Despite the promising data, the limitations of sample size and the need for further mechanistic studies are acknowledged.