LGALS9B stabilizes EEF1D protein and activates the PI3K/AKT signaling pathway to promote gastric cancer occurrence and metastasis

Abstract

Gastric cancer ranks among the most prevalent malignancies globally, characterized by limited treatment efficacy and high recurrence rates. Effective management of this disease requires a comprehensive understanding of its underlying pathogenic mechanisms. Galectins have emerged as promising targets in gastric cancer therapy, with Galectin-9 (LGALS9) receiving considerable attention in recent years. However, Galectin-9B (LGALS9B) remains relatively under-explored in gastric cancer research. Our study investigates the role of LGALS9B in gastric cancer progression, demonstrating that its over-expression enhances cellular proliferation, migration, and invasion, while its knockdown inhibits these processes both in vitro and in vivo. We further elucidate that LGALS9B competes with the E3 ligase HERC5 for binding to eukaryotic translation elongation factor 1 delta (EEF1D), thereby preventing its protein degradation. This interaction results in the enrichment of EEF1D, which activates the PI3K/AKT signaling pathway and ultimately promotes gastric cancer progression. These findings highlight the regulatory role of LGALS9B in the pathogenesis of gastric cancer, offering valuable insights into potential novel therapeutic strategies for managing this challenging disease.