FOXA3: A Novel Tumor Suppressor in Esophageal Squamous Cell Carcinoma
Abstract Background: Forkhead box A(FOXA) family, have been widely investigated in cancer research. However, currently the study of FOXA3 in malignant tumors is still limited compared with other family members. FOXA1 and FOXA2 both play a role in the development and progression of esophageal cancer and Barrett's esophagus, but the exact role of FOXA3 in esophageal squamous cell carcinoma (ESCC) has not been elucidated.Methods: The expression of FOXA3 in ESCC tissues was determined by real-time PCR immunohistochemistry staining. The relationship between FOXA3 and overall survival rate of patients was analyzed by Kaplan-Meier analysis, and Cox regression analysis was used to analyze independent prognostic risk factors. Cell proliferation was analyzed by CCK-8 assay, EdU assay and colony forming assay. Cell migration was analyzed by wound healing assay and Transwell assay. Tumorigenesis by subcutaneous injection was performed to detect the inhibition of tumors by FOXA3 in vivo.Results: We found that FOXA3 is down-regulated in ESCC tissues and low FOXA3 expression significantly correlated with a poor prognosis of ESCC. Additionally, after up-regulating the FOXA3 expression, the abilities of proliferation, migration and invasion in ESCC cells were significantly inhibited. Moreover, over-expression of FOXA3 can inhibit tumor growth in vivo either via tumorigenesis assay by subcutaneous injection.Conclusions: Low FOXA3 expression significantly correlated with a poor prognosis of ESCC and the over-expression of FOXA3 could inhibit the growth and metastasis of ESCC, which indicated that FOXA3 maybe a novel biomarker and therapeutic target for ESCC.