Elevated focal adhesion kinase expression facilitates oral tumor cell invasion

Cancer. 2002 Dec 15;95(12):2508-15. doi: 10.1002/cncr.10992.

Abstract

Background: Understanding the molecular mechanisms of metastasis is critical with respect to oral tumorigenesis. The focal adhesion kinase (FAK) is an intracellular tyrosine kinase associated with the regulation of cell growth, migration, and survival. The purpose of the current study was to determine whether elevated FAK expression in oral malignancies was associated with increased invasiveness and oral carcinoma.

Methods: Immunohistochemical analysis was used to assess levels of FAK expression in archived oral carcinoma tissue samples. Invasion assays after transfections were used to assess the effect of increased FAK expression on invasive potential of oral tumor cells.

Results: The human oral carcinoma cell line SCC25 was significantly more invasive (P < 0.05) and expressed higher levels of FAK compared with the less invasive human oral carcinoma cell line SCC15. FAK expression was 3.0-fold higher in the SCC15 cell line and 5.0-fold higher in the SCC25 cell line compared with normal epithelial cells. In the highly invasive SCC25 cell line, FAK expression was 1.5-fold higher compared with the less invasive SCC15 cell line. FAK immunostaining in oral tumors was significantly more intense compared with the immunostaining in surrounding normal epithelium or chronic mucositis. Overexpression of FAK in low-invading SCC15 cells resulted in a 4.5-fold increase in the rate of invasion compared with untransfected or neotransfected control SCC15 cell lines and a nearly 1.5-fold greater rate compared with the highly invasive untransfected SCC25 cell line.

Conclusions: The current results suggest that enhanced expression of FAK in oral carcinoma cells may lead to a selective growth advantage and increased invasive potential of the primary oral tumor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Carcinoma in Situ / enzymology*
  • Carcinoma in Situ / pathology
  • Carcinoma, Verrucous / enzymology*
  • Carcinoma, Verrucous / pathology
  • Focal Adhesion Kinase 1
  • Focal Adhesion Protein-Tyrosine Kinases
  • Focal Adhesions
  • Humans
  • Immunoenzyme Techniques
  • Mouth Neoplasms / enzymology*
  • Mouth Neoplasms / pathology
  • Neoplasm Invasiveness
  • Protein-Tyrosine Kinases / metabolism*
  • Tumor Cells, Cultured / enzymology
  • Tumor Cells, Cultured / pathology
  • Up-Regulation

Substances

  • Protein-Tyrosine Kinases
  • Focal Adhesion Kinase 1
  • Focal Adhesion Protein-Tyrosine Kinases
  • PTK2 protein, human