EphA2 promotes epithelial-mesenchymal transition through the Wnt/β-catenin pathway in gastric cancer cells.

Abstract

This study aims to investigate the significance of erythropoietin-producing hepatocellular (Eph)A2 expression and the mechanism by which EphA2 is involved in the epithelial-mensenchymal transition (EMT) of gastric cancer cells. EphA2 expression levels were upregulated and positively correlated with metastasis and EMT markers in human gastric cancer specimens. Modulation of EphA2 expression levels had distinct effects on cell proliferation, cell cycle, migration, invasion and morphology in the gastric cancer cell lines SGC7901 and AGS in vitro and in vivo. Overexpression of EphA2 resulted in the upregulation of the EMT molecular markers N-cadherin and Snail, as well as the Wnt/β-catenin targets TCF4, Cyclin-D1 and c-Myc, while silencing EphA2 using short hairpin RNA had the opposite effect. Furthermore, inhibition of the Wnt/β-catenin pathway by XAV939 negated the effect of EphA2 overexpression, whereas activation of the Wnt/β-catenin pathway by LiCl impaired the effect of the EphA2 knockdown on EMT. These observations demonstrate that EphA2 upregulation is a common event in gastric cancer specimens that is closely correlated with cancer metastasis and that EphA2 promotes EMT of gastric cancer cells through activation of Wnt/β-catenin signaling.

• Authors: J Huang, D Xiao, G Li, J Ma, P Chen, W Yuan, F Hou, J Ge, M Zhong, Y Tang, X Xia, Z Chen
• Journal: Oncogene (Oncogene) Vol. 33 Issue 21 Pg. 2737-47 (May 22 2014) ISSN: 1476-5594 [Electronic] England
• PMID: 23752181 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, CD
• CDH1 protein, human
• CDH2 protein, human
• CTNNB1 protein, human
• Cadherins
• Snail Family Transcription Factors
• Transcription Factors
• beta Catenin
• Receptor, EphA2

Topics

• Adult
• Aged
• Animals
• Antigens, CD (metabolism)
• Cadherins (metabolism)
• Cell Line, Tumor
• Cell Movement
• Cell Proliferation
• Epithelial-Mesenchymal Transition
• Female
• Gastric Mucosa (metabolism)
• Gene Expression Regulation, Neoplastic
• Humans
• Lung Neoplasms (enzymology, secondary)
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Middle Aged
• Neoplasm Transplantation
• Receptor, EphA2 (physiology)
• Snail Family Transcription Factors
• Stomach Neoplasms (enzymology, pathology)
• Transcription Factors (metabolism)
• Tumor Burden
• Up-Regulation
• Wnt Signaling Pathway
• beta Catenin (metabolism)