title: Tetraspanin 1 promotes invasiveness of cervical cancer cells.
abstract: Tetraspanins are a heterogeneous group of 4-transmembrane proteins that segregate into so-called tetraspanin-enriched microdomains (TEMs) along with other cell surface proteins such as integrins. TEMs of various types are reportedly involved in the regulation of cell growth, migration and invasion of several tumour cell types, both as suppressors or supporting structures. Tetraspanin 1 (Tspan1, NET-1), a member of the transmembrane 4 superfamily (TM4SF) of tetraspanins, is overexpressed in high-grade cervical intraepithelial neoplasia (CIN) and terminal carcinomas but its precise function in the context of carcinoma of the cervix uteri is not known. Here, we present a comprehensive investigation of the role of tetraspanin 1 in the cervical cancer cell lines SiHa and HeLa. We document that tetraspanin 1 increases the invasive potential of cervical cancer cells, whereas proliferation, growth in soft agar and adhesion are largely unaffected. In line with the latter findings, our data exclude the participation of testraspanin in integrin-mediated activation of focal adhesion kinase (FAK), paxillin and phosphoinositide-3-kinase (PI3K) and in EGFR-dependent signalling to the Ras/Erk pathway. In conclusion, our data argue against a role for tetraspanin 1 as a genuine mediator of cell surface receptor signalling but rather document a role for tetraspanin 1 in the control of cervical cancer cell motility and invasion.
authors.affiliation: Department of Gynecology and Obstretrics, Jena University Hospital, Jena, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Hölters
authors.forename: Jelena
authors.initials: J
authors.lastname: Anacker
authors.forename: Lars
authors.initials: L
authors.lastname: Jansen
authors.forename: Katrin
authors.initials: K
authors.lastname: Beer-Grondke
authors.forename: Matthias
authors.initials: M
authors.lastname: Dürst
authors.forename: Ignacio
authors.initials: I
authors.lastname: Rubio
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004789:Enzyme Activation; D066246:ErbB Receptors / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D053511:Matrix Metalloproteinase 14 / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D009361:Neoplasm Invasiveness; D051419:Paxillin / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D015398:Signal Transduction; D059470:Tetraspanins / Q000378:metabolism*; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000473:pathology*; D020703:ras GTPase-Activating Proteins / Q000378:metabolism; D002578:Uterine Cervical Dysplasia / Q000378:metabolism* / Q000473:pathology*
chemical_list: D051419:Paxillin; C508125:TSPAN1 protein, human; D059470:Tetraspanins; D020703:ras GTPase-Activating Proteins; D019869:Phosphatidylinositol 3-Kinases; C512478:EGFR protein, human; D066246:ErbB Receptors; D051416:Focal Adhesion Protein-Tyrosine Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; C507086:MMP14 protein, human; D053511:Matrix Metalloproteinase 14