The KAI1/CD82 gene suppresses metastasis in many types of human cancers. Although various ideas have been put forward to explain the mechanism by which KAI1/CD82 suppresses cancer invasiveness and metastasis, none of them is fully acceptable yet. We conducted a study on whether the KAI1/CD82 expression could change metastatic phenotype on highly metastatic carcinoma cell lines. The H1299 human lung carcinoma cells were transfected with KAI1/CD82 gene and stable transfectant clones that had a high KAI1/CD82 expression were obtained. Immunoblotting and FACS analysis were performed to confirm KAI1/CD82 expression. KAI1/CD82 transfectants show less metastatic phenotype than control transfectants and KAI1/CD82 transfectants show decreased Rac1 protein and functional activity, which suggested that KAI1/CD82 suppresses the metastatic phenotype via down-regulation of Rac1 in the human non-small-cell lung carcinoma cell lines. We further studied the signal transduction pathway to find the mechanism of rac1 down-regulation. As seen by immunoblotting assay, mTOR expression and activation were down-regulated in the KAI1/CD82 transfectants. These results demonsrated a novel pathway in which KAI1/CD82 attenuates metastatic phenotype through mTOR-mediated rac1 down-regulation in the H1299 lung carcinoma cells.

AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics-- Oct 22-26, 2007; San Francisco, CA