The HGF/c-Met signaling axis: A master regulator of invasion and metastasis in oral squamous cell carcinoma.

BACKGROUND

Oral squamous cell carcinoma (OSCC) is a major global health concern because local invasion and regional lymph node metastasis drive poor outcomes. The hepatocyte growth factor (HGF)/c-Met signaling axis is a key regulator of this aggressive phenotype.

OBJECTIVE

This narrative review evaluates evidence linking HGF/c-Met signaling to OSCC progression, tumor microenvironment interactions, treatment resistance, prognostic assessment, and therapeutic targeting.

FINDINGS: HGF/c-Met activation promotes EMT, MMP expression, cell motility, CAF-mediated crosstalk, lymphangiogenesis, perineural invasion, and EGFR inhibitor resistance through PI3K/AKT, RAS/MAPK, and STAT3 signaling. Although c-Met overexpression often correlates with poor prognosis, clinical findings are not fully consistent. Small-molecule inhibitors (crizotinib, cabozantinib, and tepotinib) and monoclonal antibodies (onartuzumab and rilotumumab) may be most useful within biomarker-guided combination regimens.

CONCLUSIONS

HGF/c-Met signaling represents a clinically relevant driver and therapeutic vulnerability in OSCC. Standardized biomarkers and rational combination strategies are required to overcome resistance and improve patient survival.