EphA8 acts as an oncogene and contributes to poor prognosis in gastric cancer via regulation of ADAM10.

Abstract

EphA8 is a member of the erythropoietin-producing hepatocellular receptor (Eph) family of receptor tyrosine kinases. Ephs and their ephrins ligands play crucial roles in many cellular processed by mediating intracellular signaling resulting from cell-cell interactions. But the underlying mechanisms of EphA8 in gastric cancer (GC) remains unclearly. 298 clinical specimens in tissues microarray, and was found to be significantly higher in GC tissues compared with nontumor tissues (p < 0.001). EphA8 expression was also strongly associated with differentiation level (p = 0.025), tumor-node-metastasis stage (p = 0.019), and poor 5 years survival (p < 0.001). A panel of GC cell lines showed reduced proliferation, invasion, and migration capacities after RNA-mediated knockdown of EphA8, concomitant with downregulation of the proliferation-related proteins (cyclin A, cyclin D1, and cyclin-dependent kinase 4) and the metastasis-related (matrix metalloproteinases MMP2, and MMP9). EphA8 knockdown also decreased expression of the protease ADAM10 (a disintegrin and metalloproteinase domain-containing protein 10) and ADAM10-related protein AKT, suggesting an interaction between EphA8 and ADAM10. In conclusion, we found that EphA8, which is highly expressed in GC tissues, stimulates proliferation, invasion, and migration of cancer cells, and is an independent risk factor for poor prognosis of GC. These dates suggest that EphA8 could be new diagnostic and/or therapeutic targets for GC.

• Authors: Yingjing Wang, Nan Zhou, Peng Li, Han Wu, Qingqing Wang, Xiaodong Gao, Xudong Wang, Jianfei Huang
• Journal: Journal of cellular physiology (J Cell Physiol) Vol. 234 Issue 11 Pg. 20408-20419 (11 2019) ISSN: 1097-4652 [Electronic] United States
• PMID: 31026069 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2019 Wiley Periodicals, Inc.

Chemical References

• Membrane Proteins
• Receptor Protein-Tyrosine Kinases
• Receptor, EphA8
• Amyloid Precursor Protein Secretases
• ADAM10 Protein
• ADAM10 protein, human

Topics

• ADAM10 Protein (metabolism)
• Amyloid Precursor Protein Secretases (metabolism)
• Cell Movement (physiology)
• Cell Proliferation (physiology)
• Gene Expression Regulation, Neoplastic (genetics)
• Humans
• Membrane Proteins (metabolism)
• Receptor Protein-Tyrosine Kinases (metabolism)
• Receptor, EphA8 (metabolism)
• Stomach Neoplasms (diagnosis, metabolism)