Overexpression of YAP confers radioresistance to esophageal cancer by altering the tumor microenvironment

Abstract This study aimed to investigate the role of yes‐associated protein (YAP) in the radiotherapy sensitivity of esophageal squamous cell carcinoma (ESCC). The clonogenic ability of ESCC cells was reduced after YAP silencing and radiotherapy. Overexpression of YAP promoted cell survival and had a synergistic effect with the hypoxic microenvironment. YAP was found to directly regulate hypoxia‐inducible factor 1α (HIF‐1α). Bioinformatics analysis revealed the involvement of YAP in modulating the tumor immune microenvironment. Inhibition of YAP expression reduced myeloid‐derived suppressor cells (MDSCs) and influenced the immunosuppressive state, leading to radio resistance. These findings provide insights into the YAP‐HIF‐1α interaction and support YAP as a potential target for enhancing radiotherapy sensitivity in esophageal cancer.