Hypoxia-inducible factor-2 alpha promotes EMT in esophageal squamous cell carcinoma through the Notch pathway

Background. Esophageal cancer is one of the most lethal tumors worldwide. The most common histological type in China is esophageal squamous cell carcinoma (ESCC), accounting for 90% of cases. Esophageal cancer occurs at a high incidence in certain areas, among which China has the highest incidence. Although various therapeutic strategies have been used in clinical treatment, the 5-year survival rate is still not satisfactory, as it is only 15-20%. The reason for the poor prognosis of ESCC is that the distant metastasis easily occurs in these tumors. However, the mechanism of metastasis has not been studied clearly. Objectives. To investigate the function of hypoxia-inducible factor-2 alpha (hif-2 alpha) in ESCC. Materials and methods. lmmunohistochemistry and immunofluorescence were used to detect the expression of hif-2 alpha in tissues and cells. Clinicopathological data from 100 ESCC patients were used to investigate the relationship between hif-2 alpha and prognosis. Cell experiments (Cell Counting Kit-8 (CCK-8) assay and transwell migration assays) were utilized to verify the roles of hif-2 alpha on the ESCC cells. Western blotting was used to explore the mechanism of hif-2 alpha in ESCC. Mouse model was used to clarify the effect of hif-2 alpha on ESCC cells in vivo. Results. The hif-2 alpha was overexpressed both in ESCC tissues and cells, and was related with poor prognosis in ESCC patients. The CCK-8 assay evidenced that silencing hif-2 alpha suppressed the proliferation of ESCC cells, while transwell assay-that overexpression of hif-2 alpha promoted the migration of ESCC cells. Western blot assay indicated that hif-2 alpha regulated epithelial-mesenchymal transition (EMT) through Notch pathway in ESCC cells. Mouse model showed that silencing hif-2 alpha significantly suppressed the proliferation of ESCC cells in vivo. Conclusions. The hif-2 alpha promotes EMT in ESCC through the Notch pathway.