title: The tetraspanin CD81 protein increases melanoma cell motility by up-regulating metalloproteinase MT1-MMP expression through the pro-oncogenic Akt-dependent Sp1 activation signaling pathways.
abstract: Despite the importance of multiple tetraspanin proteins in cancer invasion and metastasis, little is known about the role and significance of tetraspanin CD81 in these processes. In the present study, we examined CD81 effects on melanoma cell invasiveness and metastasis. Transfection of CD81 into melanoma cells lacking endogenous CD81 expression significantly enhanced the migrating, invasive, and metastatic abilities of melanoma cells. Interestingly, membrane type 1 matrix metalloproteinase (MT1-MMP) expression was found in CD81-expressing melanoma cells but not in CD81-deficient cells. siRNA knockdown of CD81 in melanoma cells with endogenous CD81 demonstrated decreased MT1-MMP levels and cell motility. Notably, CD81-induced cell migration was abrogated by antibody blocking and siRNA knockdown of MT1-MMP, indicating that MT1-MMP is responsible for CD81-stimulated melanoma cell migration. Promoter analysis revealed an essential role of the Sp1 transcription factor in CD81-induced MT1-MMP transcription. We also demonstrate that the Sp1-activating Akt pathway is involved in adhesion-dependent CD81 signaling to induce MT1-MMP expression and cell motility. Importantly, human skin cancer tissue specimens displayed a positive correlation of CD81 with MT1-MMP expression levels and a close association of CD81 with malignant melanomas. Taken together, these results strongly suggest that CD81 stimulates melanoma cell motility by inducing MT1-MMP expression through the Akt-dependent Sp1 activation signaling pathway, leading to increased melanoma invasion and metastasis.
authors.affiliation: From the Medical and Bio-Material Research Center and.
authors.forename: In-Kee
authors.initials: IK
authors.lastname: Hong
authors.affiliation: From the Medical and Bio-Material Research Center and.
authors.forename: Hee-Jung
authors.initials: HJ
authors.lastname: Byun
authors.affiliation: Brain Korea 21+ Graduate Program, Department of Biological Sciences, College of Natural Sciences, and.
authors.forename: Jaeseob
authors.initials: J
authors.lastname: Lee
authors.affiliation: From the Medical and Bio-Material Research Center and.
authors.forename: Young-June
authors.initials: YJ
authors.lastname: Jin
authors.affiliation: Department of Biological Sciences, College of Natural Sciences, and.
authors.forename: Sun-Ju
authors.initials: SJ
authors.lastname: Wang
authors.affiliation: From the Medical and Bio-Material Research Center and.
authors.forename: Doo-Il
authors.initials: DI
authors.lastname: Jeoung
authors.affiliation: Department of Molecular and Cellular Biochemistry, School of Medicine, Kangwon National University, Chunchon, Kangwon-do 200-701, Republic of Korea.
authors.forename: Young-Myeong
authors.initials: YM
authors.lastname: Kim
authors.affiliation: From the Medical and Bio-Material Research Center and Brain Korea 21+ Graduate Program, Department of Biological Sciences, College of Natural Sciences, and hslee@kangwon.ac.kr.
authors.forename: Hansoo
authors.initials: H
authors.lastname: Lee
mesh_terms: D002280:Basal Cell Carcinoma / Q000201:enzymology / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053511:Matrix Metalloproteinase 14 / Q000235:genetics* / Q000378:metabolism; D008545:Melanoma / Q000201:enzymology* / Q000556:secondary; D009361:Neoplasm Invasiveness; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology*; D012878:Skin Neoplasms / Q000201:enzymology* / Q000473:pathology; D016329:Sp1 Transcription Factor / Q000378:metabolism; D060225:Tetraspanin 28 / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology
chemical_list: C554798:CD81 protein, human; D034741:RNA, Small Interfering; D016329:Sp1 Transcription Factor; D060225:Tetraspanin 28; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt; C507086:MMP14 protein, human; D053511:Matrix Metalloproteinase 14
keywords: Cell Motility; Cell Signaling; Invasion; Melanoma; Sp1; Tetraspanins
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