Study of signal transduction of invasion / metastasis via PI3-kinase in the oral squamous cell carcinoma.

我们从口腔鳞状细胞癌(OSCC)细胞系SAS中建立了不同的侵袭性克隆，并对这两个克隆的侵袭性进行了检测，发现两个克隆的细胞运动能力有显著差异。在此，我们分析了口腔鳞状细胞癌细胞运动的信号转导。研究了磷脂酰肌醇3-激酶(PI3-K)活性在血清刺激的粘着斑激酶(p125^&lt；FAK&gt；)酪氨酸磷酸化中的作用。高侵袭性克隆SAS-H1的p125^-lt；FAK&gt；而低侵袭性克隆SAS-L1对血清的酪氨酸磷酸化反应可被Wortmannin和PI3-Kinase抑制剂LY294002明显抑制，且呈剂量依赖关系。此外，Wortmannin抑制细胞外基质的黏附和细胞运动。血清刺激PI3-激酶活性，增加SAS-H1的侵袭力，但内皮细胞单层分析不增加SAS-L1。因此，我们确定在高侵袭性口腔鳞癌细胞的细胞运动中有一条依赖PI3-激酶的信号转导通路，即SAS-H1，导致p125^&lt；FAK&gt；

We established different invasiveness clones from human oral squamous cell carcinoma (OSCC) cell line SAS.The factor that defines the invasiveness of the two clones was also examined and two clones showed remarkably different cell motility. Here we report that analyzed signal transduction of cell motility in the OSCC.The role of phosphatidyinositol 3-kinase (PI3-kinase) activity in serum-stimulated tyrosine phosphorylation of focal adhesion kinase (p125^<FAK>) has been examined. The tyrosine phosdphorylation of p125^<FAK> of high-invasion clone SAS-H1, but not low-invasion clone SAS-L1 in response to serum was markedly inhibited by both wortmannin and LY294002, inhibitor of PI3-kinase in dose dependent manner. Furthermore, wortmannin inhibited adhesiveness to extracellular matrixs and cell motility.Serum-stimulated PI3-kinase activity, increased invasion of SAS-H1, but not SAS-L1 by endothelial cell monolayr assay.Thus, we have identified a PI3-kinase dependent signal transduction pathway in the cell motility of high-invasion OSCC cells, as SAS-H1, which leads to the phosphorylation of p125^<FAK>.