title: The role of the metastasis suppressor gene KAI1 in melanoma angiogenesis.
abstract: The tetraspan protein KAI1 (CD82) has been previously shown to have important roles in cell migration, invasion, and melanoma prognosis. In this study, we investigated the role of KAI1 regarding melanoma angiogenesis. KAI1 overexpression strongly suppressed the growth of the human umbilical vein endothelial cells and their tubular structure formation in vitro. Also, KAI1 was able to inhibit both interleukin-6 (IL-6) and VEGF at mRNA and protein levels. Using nude mice in the in vivo study, we showed that KAI1, through the regulation of ING4, inhibited blood vessel formation in matrigel plugs along with the downregulation of IL-6 and VEGF, and the recruitment of CD31-positive cells. Finally, we found that KAI1 was able to suppress the activity of a serine/threonine kinase Akt by suppressing Akt phosphorylation (Ser473). Taken together, our results suggested that KAI1 was able to suppress melanoma angiogenesis by downregulating IL-6 and VEGF expression, and the restoration of KAI1 functionality offered a new approach in human melanoma treatment.
authors.affiliation: Department of Dermatology and Skin Science, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Yun
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Department of Dermatology and Skin Science, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Madhuri
authors.initials: M
authors.lastname: Bhandaru
authors.affiliation: Department of Dermatology and Skin Science, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Yabin
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Department of Dermatology and Skin Science, University of British Columbia, Vancouver, BC, Canada.|Department of Pathophysiology, Basic Medical College, Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Lu
authors.affiliation: Department of Dermatology and Skin Science, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Gang
authors.initials: G
authors.lastname: Li
authors.affiliation: Vancouver Prostate Centre, Vancouver Coastal Health Research Institute, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Ong
mesh_terms: D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D051861:Kangai-1 Protein / Q000235:genetics* / Q000378:metabolism; D008545:Melanoma / Q000098:blood supply* / Q000235:genetics / Q000473:pathology*; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic / Q000235:genetics* / Q000473:pathology; D018919:Neovascularization, Physiologic; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012878:Skin Neoplasms / Q000098:blood supply* / Q000235:genetics / Q000473:pathology*; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D018398:Homeodomain Proteins; C483230:ING4 protein, human; D015850:Interleukin-6; D051861:Kangai-1 Protein; D025521:Tumor Suppressor Proteins; D042461:Vascular Endothelial Growth Factor A; D051057:Proto-Oncogene Proteins c-akt
keywords: Akt; KAI1; VEGF; angiogenesis; inhibitor of growth 4; interleukin-6; melanoma