FOXD1 promotes proliferation, migration and epithelial-mesenchymal transformation of esophageal squamous cell carcinoma by targeting SNAI1

Abstract The transcription factor forkhead box D1 (FOXD1) is an important member of the FOX family, which is widely expressed in human embryonic cells and is thought to regulate organogenesis. It has been shown that FOXD1 could affect proliferation, migration, and angiogenesis of various tumors and its deletion and overexpression in organisms will undoubtedly have important influence on the change of cell fate and the occurrence of tumors. However, the underlying functions and molecular mechanisms of FOXD1 in esophageal squamous cell carcinoma (ESCC) have not been fully clarified. According to the present study, the expression levels and functional roles of FOXD1 were investigated, and its prognostic value and molecular mechanisms in tumorigenesis and progression of ESCC were clarified. The expression level of FOXD1 was significantly upregulated in ESCC tissues and cell lines, and correlated with TNM stage, pathological differentiation, depth of invasion, and LN metastasis. Moreover, FOXD1 promoted cells migration and invasion as well as participated in TGF-β1 induced epithelial-mesenchymal transition (EMT) process. Furthermore, a positive correlation between FOXD1 and SNAI1 was explored in ESCC. FOXD1 could directly bind to promoter regions of SNAI1 gene, leading to transcriptional promotion of SNAI1 in human esophageal cancer cells. Taken together, FOXD1 may play a tumor activator role in ESCC and may be applied as a new therapeutic target and prognostic marker for ESCC.