A new Eph receptor tyrosine kinase overexpressed in gastric cancer was found

The potential role of Eph receptor and ephrin ligand family in human cancer is receiving increasing attention. Compared with other Eph receptors, EphA4 is distinguished by its ability to bind to both type A ephrins and most type B ephrins. EphA4 reportedly forms a hetero receptor complex with FGFR1 and that EphA4/FGFR1 complex potentiates FGFR-mediated downstream signal transduction. However, alterations of EphA4 are not well understood in gastric cancer. A research article to be published on October 7, 2008 in the World Journal of Gastroenterology will adress this question. This study was conducted by a team led by Dr. Hiroyuki Yamamoto of Sapporo Medical University in which they systematically analyzed expression of EphA4, FGFR1, and ephrins in gastric cancer.

Using reverse transcription-PCR (RT-PCR), real-time RT-PCR, immunohistochemistry, and cell growth assays, the research team analyzed the expression and role of EphA4 in gastric cancer, in relation to clinicopathological characteristics and the expression of FGFR1 and ephrin ligands. EphA4 overexpression at protein level was found and significantly associated with depth of invasion, recurrence, poor prognosis, and FGFR1 overexpression. The mRNAs for ephrin ligands were coexpressed in various combinations in gastric cancer cell lines and cancer tissues. Downregulation of EphA4 expression by siRNA resulted in a significant decrease in cancer cell growth in vitro.

In the view of the team, EphA4 is the first Eph/ephrin family member of which prognostic significance was shown in gastric cancer. EphA4 reportedly forms a hetero receptor complex with FGFR1 and that the EphA4/FGFR1 complex potentiates FGFR-mediated downstream signal transduction. FGFR1 expression was correlated with EphA4 expression. Therefore, EphA4 may play a role in gastric cancer, at least in part, through the interaction with FGFR signaling.

Source: World Journal of Gastroenterology