Overexpressed HGF promotes metastasis of squamous cell carcinoma of the head and neck through the PI3K/Akt and JNK signaling pathways

Future Oncol. 2021 Nov;17(33):4527-4543. doi: 10.2217/fon-2020-1207. Epub 2021 Aug 26.

Abstract

Background: The role of HGF in squamous cell carcinoma of the head and neck (SCCHN) is not clear. Methods: Reverse transcription PCR, western blotting, gelatin zymography, immunohistochemistry, actin polymerization, chemotaxis and migration assays were used in the authors' study. Results: HGF expression level was upregulated in SCCHN cells, which was associated with clinical stage; tumor, node, metastasis classification; and lymphatic invasion. SCCHN cells with high Met expression were sensitive to cell invasion, which was blocked by inhibiting PI3K/Akt and JNK. HGF induced MMP9 expression and enhanced its activity. Akt induced the activation of JNK through the PI3K/Akt and JNK signaling pathways. Conclusion: HGF upregulates MMP9 through the activation of the PI3K/Akt and JNK signaling pathways in SCCHN cells.

Keywords: HGF; MMP9; PI3K/Akt and JNK signaling pathways; chemotaxis and migration; squamous cell carcinoma of the head and neck.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • HaCaT Cells
  • Head and Neck Neoplasms / genetics
  • Head and Neck Neoplasms / pathology*
  • Hepatocyte Growth Factor / metabolism*
  • Humans
  • Lymphatic Metastasis / genetics*
  • Lymphatic Metastasis / pathology
  • MAP Kinase Signaling System / genetics
  • Male
  • Matrix Metalloproteinase 9 / metabolism*
  • Middle Aged
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Retrospective Studies
  • Squamous Cell Carcinoma of Head and Neck / genetics
  • Squamous Cell Carcinoma of Head and Neck / secondary*
  • Up-Regulation
  • Young Adult

Substances

  • HGF protein, human
  • Hepatocyte Growth Factor
  • AKT1 protein, human
  • Proto-Oncogene Proteins c-akt
  • MMP9 protein, human
  • Matrix Metalloproteinase 9