| http://purl.uniprot.org/citations/28188308 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/28188308 | http://www.w3.org/2000/01/rdf-schema#comment | "Melanoma is well known for its propensity for lethal metastasis and resistance to most current therapies. Tumor progression and drug resistance depend to a large extent on the interplay between tumor cells and the surrounding matrix. We previously identified Tetraspanin 8 (Tspan8) as a critical mediator of melanoma invasion, whose expression is absent in healthy skin. The present study investigated whether Tspan8 may influence cell-matrix anchorage and regulate downstream molecular pathways leading to an aggressive behavior. Using silencing and ectopic expression strategies, we showed that Tspan8-mediated invasion of melanoma cells resulted from defects in cell-matrix anchorage by interacting with β1 integrins and by interfering with their clustering, without affecting their surface or global expression levels. These effects were associated with impaired phosphorylation of integrin-linked kinase (ILK) and its downstream target Akt-S473, but not FAK. Specific blockade of Akt or ILK activity strongly affected cell-matrix adhesion. Moreover, expression of a dominant-negative form of ILK reduced β1 integrin clustering and cell-matrix adhesion. Finally, we observed a tumor-promoting effect of Tspan8 in vivo and a mutually exclusive expression pattern between Tspan8 and phosphorylated ILK in melanoma xenografts and human melanocytic lesions. Altogether, the in vitro, in vivo and in situ data highlight a novel regulatory role for Tspan8 in melanoma progression by modulating cell-matrix interactions through β1 integrin-ILK axis and establish Tspan8 as a negative regulator of ILK activity. These findings emphasize the importance of targeting Tspan8 as a means of switching from low-to firm-adhesive states, mandatory to prevent tumor dissemination."xsd:string |
| http://purl.uniprot.org/citations/28188308 | http://purl.org/dc/terms/identifier | "doi:10.18632/oncotarget.15084"xsd:string |
| http://purl.uniprot.org/citations/28188308 | http://purl.uniprot.org/core/author | "Robert C."xsd:string |
| http://purl.uniprot.org/citations/28188308 | http://purl.uniprot.org/core/author | "Dedhar S."xsd:string |
| http://purl.uniprot.org/citations/28188308 | http://purl.uniprot.org/core/author | "de la Fouchardiere A."xsd:string |
| http://purl.uniprot.org/citations/28188308 | http://purl.uniprot.org/core/author | "Le Naour F."xsd:string |
| http://purl.uniprot.org/citations/28188308 | http://purl.uniprot.org/core/author | "Masse I."xsd:string |
| http://purl.uniprot.org/citations/28188308 | http://purl.uniprot.org/core/author | "McDonald P.C."xsd:string |
| http://purl.uniprot.org/citations/28188308 | http://purl.uniprot.org/core/author | "Gadot N."xsd:string |
| http://purl.uniprot.org/citations/28188308 | http://purl.uniprot.org/core/author | "Degoul F."xsd:string |
| http://purl.uniprot.org/citations/28188308 | http://purl.uniprot.org/core/author | "Berthier-Vergnes O."xsd:string |
| http://purl.uniprot.org/citations/28188308 | http://purl.uniprot.org/core/author | "Barbollat-Boutrand L."xsd:string |
| http://purl.uniprot.org/citations/28188308 | http://purl.uniprot.org/core/author | "El Kharbili M."xsd:string |
| http://purl.uniprot.org/citations/28188308 | http://purl.uniprot.org/core/author | "Danty-Berger E."xsd:string |
| http://purl.uniprot.org/citations/28188308 | http://purl.uniprot.org/core/author | "Witkowski T."xsd:string |
| http://purl.uniprot.org/citations/28188308 | http://purl.uniprot.org/core/date | "2017"xsd:gYear |
| http://purl.uniprot.org/citations/28188308 | http://purl.uniprot.org/core/name | "Oncotarget"xsd:string |
| http://purl.uniprot.org/citations/28188308 | http://purl.uniprot.org/core/pages | "17140-17155"xsd:string |
| http://purl.uniprot.org/citations/28188308 | http://purl.uniprot.org/core/title | "Tetraspanin 8 is a novel regulator of ILK-driven beta1 integrin adhesion and signaling in invasive melanoma cells."xsd:string |
| http://purl.uniprot.org/citations/28188308 | http://purl.uniprot.org/core/volume | "8"xsd:string |
| http://purl.uniprot.org/citations/28188308 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/28188308 |
| http://purl.uniprot.org/citations/28188308 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/28188308 |
| http://purl.uniprot.org/uniprot/#_Q53GA9-mappedCitation-28188308 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/28188308 |
| http://purl.uniprot.org/uniprot/#_P19075-mappedCitation-28188308 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/28188308 |