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

我们从人口腔鳞癌细胞系SAS中建立了不同侵袭力的克隆，并对决定这两个克隆侵袭力的因素进行了研究，发现两个克隆的细胞运动能力有显著差异。本研究分析了OSCC中细胞运动的信号转导途径，研究了磷脂酰肌醇3-激酶（PI 3-kinase）活性在血清刺激的黏着斑激酶（p125）酪氨酸磷酸化中的作用<FAK>。wortmannin<FAK>和PI 3-激酶抑制剂LY 294002均能剂量依赖性地抑制高侵袭性克隆SAS-H1的p125 β酪氨酸磷酸化，而对低侵袭性克隆SAS-L1的p125 β酪氨酸磷酸化无影响。结果表明，wortmannin可抑制细胞的侵袭能力，抑制细胞的运动能力，而血清刺激的PI 3激酶活性可增加SAS-H1的侵袭能力，但对SAS-L1无影响，因此，我们确定了SAS-H1是一条PI 3激酶依赖的细胞运动信号通路，它导致p125磷酸化<FAK>。

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>.