Ephrin-A4 Ligand Promotes Gastric Cancer Cell Epithelial-Mesenchymal Transition Via The PI3K/AKT Signaling Pathway

Background Ephrin A4 (EFNA4), a member of the ephrin ligand family, is implicated in the progression of multiple malignant tumors. However, its functional role in gastric cancer (GC) remains poorly understood. Thus, this study was designed to investigate the potential mechanisms through which EFNA4 operates in GC. Methods and results Firstly, bioinformatic assessments indicated significantly elevated levels of EFNA4 in GC tissues compared to normal tissues. Secondly, Clinical data from a cohort of 93 GC patients further demonstrated associations between EFNA4 expression and differentiation, tumor size, as well as TNM stage. Furthermore, high EFNA4 expression was correlated with reduced overall survival, indicating its prognostic significance. Thirdly, In vitro experiments revealed that silencing EFNA4 suppressed the proliferation, invasion, and migratory capacity of GC cells. Additionally, knockdown of EFNA4 inhibited epithelial-mesenchymal transition (EMT) by modulating the PI3K/AKT signaling cascade. Treatment with 740Y-P, a PI3K activator, enhanced the expression of PI3K/AKT-related proteins but did not affect the expression of EFNA4. Conclusions These findings indicate that EFNA4 may act as an upstream regulator within the PI3K/AKT signaling axis, playing a key regulatory role in the EMT process during GC progression.