1. Interaction between the EPHB2 receptor and EFNB1 ligand drives gastric cancer invasion and metastasis via the Wnt/β-catenin/FAK pathway.
- Author
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Hu, Yaohua, Xie, Qinghua, Zhao, Jumei, Yang, Runze, Qin, Jing, Li, Hui, Zhao, Yong, Du, Xiong, and Shi, Changhong
- Subjects
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STOMACH cancer , *METASTASIS , *EPHRIN receptors , *GENE therapy , *CELLULAR signal transduction , *WNT signal transduction , *CATENINS - Abstract
The survival benefit for patients with gastric cancer (GC) is modest due to its high transfer potential. Targeted therapy for metastasis-related genes in GC may be a viable approach, however, inhibitors specifically targeting GC are limited. In this study, GC patient-derived xenografts (PDX) with metastatic burden were established via orthotopic transplantation. PCR-Array analysis of primary and metastatic tumors revealed EPH receptor B2 (EPHB2) as the most significantly upregulated gene. The interaction between the EPHB2 receptor and its cognate-specific EFNB1 ligands was high in GC and correlated with a poor prognosis. Fc-EFNB1 treatment increased the invasion and migration abilities of GC cells and induced a high EPHB2 expression. EPHB2 knockdown in GC cells completely abolished the ephrin ligand-induced effects on invasion and migration abilities. Signal transduction analysis revealed Wnt/β-catenin and FAK as downstream signaling mediators potentially inducing the EPHB2 phenotype. In conclusion, the observed deregulation of EPHB2/EFNB1 expression in GC enhances the invasive phenotype, suggesting a potential role of EPHB2/EFNB1 compound in local tumor cell invasion and the formation of metastasis. [Display omitted] • EPHB2 and EFNB1 are co-expressed in gastric cancer cells and tissues. • The interaction between EPHB2 and EFNB1 significantly promoted gastric cancer metastasis. • EPHB2/EFNB1 compounds are potential indicators for the diagnosis of gastric cancer metastasis. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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