Activation of phosphatdylinositol 3-kinase by serum stimulation enhances cell adhesion and cell motility in highly-invasive tongue squamous cell carcinoma cells, SAS-H1.

We investigated the role of phosphatidylinositol 3-kinase (PI 3 K) in tumor cell invasion. Two cloned tumor cell lines, designated SAS-L 1 (low invasiveness) and SAS-H 1 (high invasiveness), were isolated from a human oral squamous cell carcinoma (OSCC), SAS. SAS-L 1 and SAS-H 1 cells exhibited high and low motility, respectively. To compare the function of PI 3 K between the two tumor lines, the signaling mechanism after serum stimulation was examined.In SAS-H 1 cells, tyrosine phosphorylation of focal adhesion kinase (p125FAK) in response to serum stimulation was markedly inhibited by both wortmannin and LY294002, a dosedependent inhibitor of PI 3 K, but inhibition was not observed in SAS-L 1 cells. Futhermore, wortmannin inhibited adhesiveness to extracellular matrices and cell motility in SAS-H 1 cells.PI 3 K activity induced by serum stimulation was higher in SAS-H 1 cells than in SAS-L 1 cells. Activation of PI 3 K was abolished by wortmannin or LY294002. The correlation between PI 3 K activation and invasive potential suggested that inhibition of activated PI 3 K would decrease the invasiveness of SAS-H 1 cells. Wortmannin or LY294002 inhibited invasion by SAS-H 1 cells, but not SAS-L 1 cells on endothelial monolayer invasion assay.Our results suggest that a PI 3 K-dependent signal transduction pathway plays an essential role in cell adhesion and cell motility of the highly-invasive OSCC cell line (SAS-H 1), which leads to the phosphorylation of p125FAK.