2013
DOI: 10.1038/onc.2013.238
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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 ce… Show more

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Cited by 178 publications
(165 citation statements)
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“…Aberrant Wnt/β‐catenin signaling is known to play an important role in the initiation and maintenance of GC (Hidaka et al ., 2013; Ju et al ., 2014). While Wnt signaling is activated, β‐catenin is stabilized and accumulates in the cytoplasm and then migrates to the nucleus where it binds to the T‐cell factor/lymphoid enhancer‐binding factor (TCF/LEF) to promote transcription of various target genes, inducing those related to EMT (Clevers, 2006; Clevers and Nusse, 2012; Huang et al ., 2014). In the present study, we found that DDAH1 overexpression significantly decreased the level of β‐catenin, whereas its knockdown produced the opposite effect.…”
Section: Discussionmentioning
confidence: 99%
“…Aberrant Wnt/β‐catenin signaling is known to play an important role in the initiation and maintenance of GC (Hidaka et al ., 2013; Ju et al ., 2014). While Wnt signaling is activated, β‐catenin is stabilized and accumulates in the cytoplasm and then migrates to the nucleus where it binds to the T‐cell factor/lymphoid enhancer‐binding factor (TCF/LEF) to promote transcription of various target genes, inducing those related to EMT (Clevers, 2006; Clevers and Nusse, 2012; Huang et al ., 2014). In the present study, we found that DDAH1 overexpression significantly decreased the level of β‐catenin, whereas its knockdown produced the opposite effect.…”
Section: Discussionmentioning
confidence: 99%
“…On the other hand, nuclear b-catenin is correlated with an invasive phenotype in intestinal-type tumors [198] . This increase in tumor invasion is likely mediated by the upregulation of Wnt transcriptional targets, such as EphA2 (erythropoietin-producing hepatocellular) and membrane type 3 matrix metalloproteinase (MT3-MMP) genes [199,200] . Furthermore, evidence provided by Kim et al [201,202] suggests that TC1 (C8orf4), which is upregulated in high-grade gastric cancers, coordinates the upregulation of Wnt/b-catenin target genes involved in the aggressive biological behavior and poor clinical outcome observed in advanced gastric cancer [202,203] .…”
Section: Wnt/b-catenin Signaling and Metastatic Potential In Gastric mentioning
confidence: 99%
“…Expression of EphA1 and EphA2 is associated with poor prognosis in gastric cancer. 115,116 Increased EphA1 expression significantly correlated with increased tumor grade and lymph node metastasis and decreased cumulative survival in gastric carcinomas. Ephrin-A1 mRNA transcripts independently predicted poor prognosis in colorectal cancer patients and knockdown of this ligand inhibited proliferation and migration of colon carcinoma cell lines.…”
Section: Eph Receptor and Ephrin Signaling In Gastrointestinal Diseasementioning
confidence: 99%