Metastasis suppressor KAI1/CD82 attenuates the matrix adhesion of human prostate cancer cells by suppressing fibronectin expression and β1 integrin activation.
KAI1, a metastasis-suppressor gene belonging to the tetraspanin family, is known to inhibit cancer metastasis without affecting the primary tumorigenicity by inhibiting the epidermal growth factor (EGF) signaling pathway.
KAI1/CD82 has been reported to attenuate the process of metastases in a variety of tumors; however, its mechanism of action in invasion has not been fully elucidated.
KAI1 COOH-terminal interacting tetraspanin (KITENIN) has been found to act as a promoter of metastasis in murine models of colon cancer and squamous cell carcinoma (SCC).
CD82 suppresses metastasis by multiple mechanisms including inhibition of cell motility and invasion, promotion of cell polarity as well as induction of senescence and apoptosis in response to extracellular stimuli.
KAI1 may be involved in retinoblastoma metastasis, and increased expression of KAI1 significantly inhibits the metastatic ability of RB cells <i>in vitro</i>.
A recent study showed that the synergism of wild-type p53 and JunB has the function of regulating the expression of KAI1, a metastasis inhibiting factor in prostate cancer cells.
Additionally, advanced and metastasized tumor tissues revealed significantly down-regulated CD82 protein expression (p = 0.033 and p = 0, respectively), which correlated with the tumor pTNM stage (p = 0.001).
Affymetrix gene expression profiling, combined with gain- and loss-of-function analyses and chromatin immunoprecipitation, indicated that cluster of differentiation 82 (CD82), a documented metastasis suppressor, is a direct transcriptional target of ΔNp63α.
Although the KAI1/CD82 protein has been reported to inhibit cell metastasis in many studies, its mechanism of action has not yet been fully elucidated.
Because metastasis formation is a critical step in tumor progression and a negative prognostic factor, we compared the expression of nm23-H1 and KAI1, two metastasis-suppressing genes, in papilla of Vater cancer and pancreatic cancer.
By contrast, KAI1 mRNA expression was significantly correlated with gender (P=0.047), metastasis to the lymph nodes or other organs (P=0.004), the histological grade of the tumor (P=0.036) and the pathological stage (P=0.049).