Abstract
BackgroundThe erythropoietin-producing hepatocellular (Eph) receptor A5 (EphA5) has been found to be overexpressed in some malignant tumors and is associated with disease prognosis. However, the role of EphA5 in esophageal squamous cell carcinoma (ESCC) is not clear.MethodsIn the present study, we measured the expression of EphA5 in ESCC tissues and cell lines including KYSE150 and KYSE450 cells. siRNA transfection was used to interfere with EphA5 expression in ESCC cell lines. Cell viability, colony formation, scratch and invasion assays were performed to explore the roles of EphA5 in ESCC cell lines. Flow cytometry analysis was performed to investigate whether EphA5 could affect the cell apoptosis and cycle. The biomarkers related to epithelial-mesenchymal transition (EMT) and molecules associated with Wnt/β‑catenin signaling were also measured by western blot and immunofluorescence.ResultsThe protein and mRNA expression of EphA5 were significantly higher in fresh ESCC tissues and cell lines compared with normal control groups and human normal esophageal epithelial cells (HEEC). The cell viability assay and colony formation assay revealed that EphA5 knockdown enhanced the proliferation of KYSE150 and KYSE450 cells in vitro. The invasion and migration of ESCC cells were accelerated after EphA5 knockdown. The expression of EMT biomarkers was altered in ESCC cells transfected with siRNA targeting EphA5. Moreover, EphA5 downregulation enhanced the protein levels of β‑catenin and p-GSK-3βSer9, which play a key role in the Wnt/β‑catenin pathway.ConclusionsEphA5 knockdown promotes the proliferation of esophageal squamous cell carcinoma,enhances invasion and migration ability via epithelial-mesenchymal transition through activating Wnt/β‑catenin pathway.
Highlights
The erythropoietin-producing hepatocellular (Eph) receptor A5 (EphA5) has been found to be overex‐ pressed in some malignant tumors and is associated with disease prognosis
Contradictory with the above reports, we found that high erythropoietin-producing hepatocellular receptor A5 (EphA5) expression implies a greater likelihood of regional lymph node metastasis and advanced tumor stage, while low EphA5 expression may be related to nerve invasion
The results demonstrated that the level of E-cadherin in the EphA5 knockdown cells was downregulated whereas the levels of N-cadherin and Snail were upregulated compared with the negative controls
Summary
The erythropoietin-producing hepatocellular (Eph) receptor A5 (EphA5) has been found to be overex‐ pressed in some malignant tumors and is associated with disease prognosis. The role of EphA5 in esopha‐ geal squamous cell carcinoma (ESCC) is not clear. There are two main subtypes: esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC). Erythropoietin-producing human hepatocellular carcinoma receptors (Eph receptors) are the largest subgroup of the receptor tyrosine kinases family. It was first identified in human cancers,and has been found to play important roles in pathology and physiology [3]. Depending on their ephrin ligands, Eph receptors are subdivided into EphA or EphB subfamilies [4]. The role of EphA5 in patients with ESCC remains unknown
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