title: 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.
authors.affiliation: Department of Dermatology and Skin Science.
authors.forename: Yun
authors.initials: Y
authors.lastname: Tang
authors.forename: Yabin
authors.initials: Y
authors.lastname: Cheng
authors.forename: Magdalena
authors.initials: M
authors.lastname: Martinka
authors.forename: Christopher John
authors.initials: CJ
authors.lastname: Ong
authors.forename: Gang
authors.initials: G
authors.lastname: Li
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement; D002648:Child; D004416:Dysplastic Nevus Syndrome / Q000378:metabolism / Q000473:pathology; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051861:Kangai-1 Protein / Q000235:genetics / Q000378:metabolism*; D008297:Male; D020778:Matrix Metalloproteinase 2; D008545:Melanoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D012878:Skin Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult
chemical_list: C497688:CD82 protein, human; D018797:Cell Cycle Proteins; D018398:Homeodomain Proteins; C483230:ING4 protein, human; D051861:Kangai-1 Protein; D025521:Tumor Suppressor Proteins; D020778:Matrix Metalloproteinase 2