Prognostic significance of KAI1/CD82 in human melanoma and its role in cell migration and invasion through the regulation of ING4

Abstract

KAI1/CD82 is a member of the transmembrane 4 superfamily, which was first identified as a metastasis suppressor for prostate cancer. The expression of KAI1 was found to be reduced in many types of cancers, including prostate, breast, ovarian, cervical and endometrial cancer. However, the role of KAI1 in melanoma pathogenesis is not known. In this study, we investigated the expression level of KAI1 in a large set of melanocytic lesions at different stages. We found that the expression of KAI1 is significantly decreased during melanoma progression. In fact, KAI1 expression is drastically reduced in primary melanoma compared with dysplastic nevi (P = 1.8×10(-4)) and further reduced in metastatic melanoma compared with primary melanoma (P = 9.4 × 10(-15)). Furthermore, decreased KAI1 staining is strongly correlated with a worse 5 year and 10 year patient survival. Multivariate Cox regression analysis showed that KAI1 is also an independent prognostic factor for both 5 year and 10 year survival. Moreover, we found that overexpression of KAI1 significantly inhibited melanoma cell migration through suppression of Rho-associated kinase-mediated formation of stress fiber. Our data also suggested that overexpression of KAI1 significantly inhibited melanoma cell invasion by reducing the activity of metalloproteinase-2. In addition, we found that suppression of melanoma cell migration by KAI1 is mediated by another tumor-suppressor protein called inhibitor of growth 4 through the regulation of p65. Taken together, our data suggest that KAI1 may be used as a promising prognostic marker and a possible therapeutic target for human melanoma.

Characteristics of the expression of KAI1/CD82 and PDGFRβ and their impact on glioma progression

“…Secondly, the other function of KAI1/CD82 protein could be considered in gliomas like regulation by microRNA. An experimental study has shown that KAI1/CD82 is able to inhibit the signaling PI3K/AKT pathway in breast, bladder, and melanoma cancer cell lines [23,24]. Taking into account that the PI3K/ AKT pathway is often activated by PDGFR receptors during glioma progression, we suggest that the suppression of the PI3K/AKT pathway by KAI1/CD82 protein might limit the proliferation and spread of glioma cells [19,23].…”

“…Recently, data revealed that upregulation of micro-RNA-210 induced cell proliferation and migration of glioblastoma cells [32]. We postulate that KAI1/CD82 protein expression in gliomas might play a similar role to that in tumors with metastasis to other organs [7,23]. Firstly, KAI1/CD82 as a metastasis suppressor protein might inhibit the migratory ability of glioma cells, so we suggest that a high expression of KAI1/CD82 in low grade gliomas might reduce the risk of secondary glioblastoma development.…”

“…Several mechanisms have been proposed by which KAI1/CD82 might influence and control tumor cell behavior [29]. It was established that KAI1/CD82 plays an important role in regulating melanoma cell migration through the controlling of Rho and GTPases signaling activity [23]. Another study revealed that KAI1/CD82 might have an inhibitory role in the PI3K/AKT pathway [1,6,23].…”

“…It was established that KAI1/CD82 plays an important role in regulating melanoma cell migration through the controlling of Rho and GTPases signaling activity [23]. Another study revealed that KAI1/CD82 might have an inhibitory role in the PI3K/AKT pathway [1,6,23]. So far, the correlation between KAI1/CD82 expression and the signal transduction pathway has been examined in breast and ovarian cancers [29].…”

The Effects of Cytotoxic Dose of Diclofenac on CD82/KAI1 in Cervical Cancer Cells in Cell Culture

“…[14] The studies suggest that KAI1 may be used as a promising prognostic marker and a possible therapeutic target for human melanoma. [15] Decreased KAI1 expression has been observed recently in various human cancers, including pancreatic, lung, hepatic, colorectal, breast, ovarian, esophageal, and cervical cancers. Frequent down-regulation of the KAI1 protein was also observed in endometrial cancer cell lines.…”