Hepatocyte growth factor/c-Met signaling axis in human diseases: Mechanistic insights and therapeutic potential

Hepatocyte growth factor (HGF) is a multifunctional cytokine that activates the tyrosine kinase activity of its specific receptor, c-Met (mesenchymal-epithelial transition factor). This activation subsequently regulates downstream signaling pathways such as PI3K/Akt and Ras/MEK, ultimately mediating key biological processes including epithelial cell migration, proliferation, morphogenesis, and damaged tissue regeneration. Accumulating evidence indicates that the HGF/c-Met pathway is critical for embryonic development and tissue homeostasis. Dysregulation of this pathway-whether excessive activation or suppression-is closely associated with the pathogenesis of numerous human diseases. This review systematically synthesizes recent research data on the HGF/c-Met pathway and elucidates its disease-related mechanisms: it promotes malignant tumor progression, participates in viral infectious disease pathogenesis, facilitates tissue injury repair, and is implicated in diabetes mellitus and Alzheimer's disease. It further clarifies the pathway's fundamental biological functions, summarizes potential therapeutic strategies targeting this pathway (e.g., c-Met inhibitors, HGF antagonists, and microRNA-mediated regulation), and discusses challenges in clinical translation (e.g., poor target specificity and drug resistance), providing a theoretical reference for subsequent disease-targeted therapy research.