OVOL1 targets YAP to suppress esophageal squamous cell carcinoma progression.

BACKGROUND Abnormal regulation of OVO-like proteins (OVOLs) has been recognized as an important contributor to cancer development. Ovo like transcriptional repressor 1 (OVOL1), a member of the OVOL family, has been reported to function either as a tumor suppressor or as an oncogene in different cancer types; however, its role in esophageal squamous cell carcinoma (ESCC) has not been clearly defined.

METHODS The expression of OVOL1 in ESCC was examined using multiple independent patient cohorts, and its clinical significance was further evaluated. The functional role of OVOL1 in ESCC cells was determined through both in vitro and in vivo experiments. To elucidate the underlying mechanisms, RNA-seq, luciferase reporter, co-immunoprecipitation, and chromatin immunoprecipitation (ChIP) assays were performed.

RESULTS Reduced OVOL1 expression was frequently observed across multiple ESCC cohorts and was associated with poor clinical outcomes. Both in vitro and in vivo experiments showed that enforced OVOL1 expression suppresses ESCC cell proliferation, stemness-associated traits, and lung metastasis caused by tail vein injection of ESCC cells in mice, whereas OVOL1 knockdown enhances these malignant behaviors. Mechanistically, OVOL1 represses Yes1-associated transcriptional regulator (YAP) transcription, which is likely achieved through a histone deacetylase (HDAC)-dependent mechanism, thereby limiting ESCC progression.

CONCLUSION OVOL1 acts as a tumor suppressor in ESCC, in part by suppressing YAP.