BACKGROUND: The forkhead box A (FOXA) family has been extensively studied in cancer research
however, the role of FOXA3 in malignant tumors, particularly esophageal squamous cell carcinoma (ESCC), is not well understood. This study explores the expression and function of FOXA3 in ESCC, assessing its potential as a prognostic marker and therapeutic target. METHODS: This study analyzed FOXA3 expression in ESCC tissues and its correlation with patient prognosis. The effects of FOXA3 overexpression on ESCC cell proliferation, migration, and invasion were examined in ESCC cell lines in vitro. Additionally, an in vivo tumorigenesis assay was performed using subcutaneous injection to assess the impact of FOXA3 overexpression on tumor growth. Statistical analyses were conducted to determine the significance of the results. RESULTS: FOXA3 expression was significantly reduced in ESCC tissues compared with it in paired adjacent normal tissues, and low FOXA3 expression was significantly associated with poor prognosis in ESCC patients. FOXA3 overexpression markedly inhibited ESCC cell proliferation, migration, and invasion. In addition, overexpression of FOXA3 repressed tumor growth in mice. CONCLUSIONS: These findings indicate that FOXA3 acts as a tumor suppressor in ESCC, and its low expression is linked to poor outcomes. FOXA3 may serve as a potential diagnostic and therapeutic target for ESCC.