LIF/LIFR Signaling in Gastric Cancer: A Double-Edged Sword in Tumor Progression and Therapeutic Resistance.

Gastric cancer (GC) remains a major cause of cancer-related mortality worldwide, driven by late-stage diagnoses and poor survival outcomes. Leukemia inhibitory factor (LIF) and leukemia inhibitory factor receptor (LIFR) are increasingly recognized as critical players in GC pathophysiology, though their exact roles are not fully understood. LIF, a multifunctional cytokine in the interleukin-6 family, signals through the LIFR/gp130 complex and activates oncogenic pathways such as JAK/STAT3, MAPK/ERK, and Hippo-YAP. Emerging evidence indicates that LIF drives tumor progression by promoting epithelial-mesenchymal transition, immune evasion, and chemoresistance. Clinically, high LIF expression is associated with poor prognosis, peritoneal metastasis, and resistance to chemotherapy and immunotherapy. This review explores the molecular mechanisms of LIF/LIFR signaling in GC, highlighting its potential as a prognostic biomarker and therapeutic target. MINI ABSTRACT CONCLUSION: The LIF/LIFR pathway contributing to gastric cancer is complex with context-dependent pro- versus anti-tumorigenic roles in GC progression, marking it as a significant biomarker and target for future therapies.