Elevated focal adhesion kinase expression facilitates oral tumor cell invasion.
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.
Schneider
Galen B
GB
Department of Prosthodontics and Dows Institute for Dental Research, College of Dentistry, University of Iowa, Iowa City, Iowa 52242, USA. galen-schneider@uiowa.edu
Kurago
Zoya
Z
Zaharias
Rebecca
R
Gruman
Lynn M
LM
Schaller
Michael D
MD
Hendrix
Mary J C
MJ
D000818:Animals; D015153:Blotting, Western; D002278:Carcinoma in Situ / Q000201:enzymology* / Q000473:pathology; D018289:Carcinoma, Verrucous / Q000201:enzymology* / Q000473:pathology; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D022001:Focal Adhesions; D006801:Humans; D007124:Immunoenzyme Techniques; D009062:Mouth Neoplasms / Q000201:enzymology* / Q000473:pathology; D009361:Neoplasm Invasiveness; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000201:enzymology / Q000473:pathology; D015854:Up-Regulation
D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human