FBXW7 inhibits the Progression of ESCC by directly inhibiting the Stemness of Tumor Cells

Abstract

Background F-box and WD repeat domain containing 7 (FBXW7), is an aboriginal and high frequency mutant gene associated with esophageal squamous cell carcinoma (ESCC). This study was designed to determine the clinical value and molecular mechanisms of FBXW7 in the development of ESCC. Methods The clinical significance of FBXW7 was analyzed in ESCC from TCGA data. The effects of FBXW7 on proliferation, colony formation, migration and invasion, angiogenesis and apoptosis were tested in ESCC cells. PCR-array, sphere formation assay, quantitative real-time polymerase chain reaction(qPCR) were used to explore the mechanism of FBXW7. Results FBXW7 was a significantly mutated gene in ESCC. It was an independent and potential predictor for survival in ESCC patients. In addition, FBXW7 overexpression significantly inhibited ESCC cell proliferation, migration, invasion, angiogenesis, and promoted cell apoptosis. PCR-array revealed that FBXW7 overexpression leads to a significant change of genes expression associated with angiogenesis, cell senescence and DNA damage and repair. Sphere formation assay and qPCR showed FBXW7 was associated with ESCC stem cell formation. Conclusions Our results suggest that FBXW7 may act as a tumor suppressor by repressing cancer stem cell formation and regulating tumor angiogenesis, cell senescence, DNA damage and repair in ESCC.