in T-cadherin expression in cultured VSMCs. Expression of T-cadherin leads to complete inhibition of subcutaneous tumor growth in nude mice. Seeding T-cadherin expressing cells on plastic coated with recombinant aminoterminal fragments of T-cadherin resulted in suppression of cell growth and was found to be associated with increased expression of p21. In T-cadherin deficient C6 glioma cell lines, its overexpression results in growth suppression involving p21CIP1/WAF1 production and G2 arrest. T-cadherin loss in tumor cells is associated with tumor malignancy, invasiveness and metastasis. Thus, tumor progression in basal cell carcinoma, cutaneous squamous carcinoma, non-small cell lung carcinoma (NSCLC), ovarian cancer, pancreatic cancer, colorectal cancer correlates with downregulation of T-cadherin expression. In psoriasis vulgaris the hyperproliferation of keratinocytes also correlates with the downregulation of T-cadherin expression. The mechanism for T-cadherin suppression is associated with allelic loss or hypermethylation of the T-cadherin gene promoter region. Transfection of T-cadherin negative neuroblastoma TGW and NH-12 cells with T-cadherin results in their loss of mitogenic proliferative response to epidermal growth factor (EGF) growth stimulation. Re-expression of T-cadherin in human breast cancer cells (MDAMB435) in culture, which originally do not express T-cadherin, results in the change of the phenotype from invasive to normal epithelial-like morphology. Thus, it was hypothesized that T-cadherin functions as a tumor-suppressor factor; inactivation of T-cadherin is associated with tumor malignancy, invasiveness and metastasis. However, in other tumors T-cadherin expression could promote tumor growth and metastasis. In primary lung tumors the loss of T-cadherin was not attributed to the presence of metastasis in lymph nodes, and in osteosarcomas T-cadherin expression was correlated with metastasis. Furthermore, T-cadherin overexpression was found to be a common feature of human high grade astrocytomas and associated with malignant transformation of astrocytes. Hetezygosity for NF1 (neurofibromatosis 1) tumor suppressor resulting in reduced attachment and spreading and increased motility also coincides with upregulated T-cadherin expression. Data show that HUVEC cells overexpressing T-cadherin after adenovirus infection enter S-phase more rapidly and exhibit increased proliferation potential. T-cadherin expression increases in HUVEC under conditions of oxidative stress, and production of reactive oxygen species (ROS) contributes to T-cadherin elevated expression. T-cadherin overexpression in HUVEC leads to higher phosphorylation of Phosphatidylinositol 3-kinase (PIK3) – target of Akt, and mTOR – target p70S6K (survival pathway regulator), resulting in reduced levels of caspase activation and increased survival after exposure to oxidative stress. It was suggested that in vascular cells T-cadherin performs a protective role against stress-induced apoptosis. Tumor