The Role of Yes-Associated Protein in Autophagy and Tumor Progression in Gastric Cancer.

Abstract

The Yes-associated protein (YAP) is a key regulator in the pathogenesis of gastric cancer (GC), yet its role in modulating autophagy remains unclear. This study investigated the effects of YAP modulation on autophagy and tumor progression using the SNU-484 and MKN-74 gastric cancer cell lines. YAP overexpression led to increased B-cell lymphoma-2 (BCL-2) transcription, reducing autophagy and enhancing cell survival, while YAP knockdown resulted in elevated autophagic activity. In vivo experiments with nude mice confirmed that YAP overexpression promotes tumor growth, whereas YAP silencing inhibits it. Further analysis revealed that YAP directly binds to the BCL-2 promoter, driving its transcription and thereby inhibiting autophagy-induced cell death. Importantly, silencing BCL-2 mitigated the autophagy inhibition caused by YAP without affecting YAP expression itself. These findings indicate that YAP, by upregulating BCL-2, suppresses autophagy and contributes to gastric cancer progression, suggesting a potential therapeutic strategy targeting the YAP-BCL-2 axis in GC treatment.