Fiche publication
Date publication
janvier 2016
Journal
Oncotarget
Auteurs
Membres identifiés du Cancéropôle Est :
Dr BRASSART-PASCO Sylvie
,
Dr MONBOISSE Jean-Claude
,
Pr RAMONT Laurent
,
Dr BRASSART Bertrand
,
Dr OUDART Jean-Baptiste
Tous les auteurs :
Oudart JB, Doué M, Vautrin A, Brassart B, Sellier C, Dupont-Deshorgue A, Monboisse JC, Maquart FX, Brassart-Pasco S, Ramont L
Lien Pubmed
Résumé
Type XIX collagen is a minor collagen associated with basement membranes. It was isolated for the first time in a human cDNA library from rhabdomyosarcoma and belongs to the FACITs family (Fibril Associated Collagens with Interrupted Triple Helices). Previously, we demonstrated that the NC1 domain of collagen XIX (NC1(XIX)) exerts anti-tumor properties on melanoma cells by inhibiting their migration and invasion. In the present work, we identified for the first time the integrin αvβ3 as a receptor of NC1(XIX). Moreover, we demonstrated that NC1(XIX) inhibits the FAK/PI3K/Akt/mTOR pathway, by decreasing the phosphorylation and activity of the major proteins involved in this pathway. On the other hand, NC1(XIX) induced an increase of GSK3β activity by decreasing its degree of phosphorylation. Treatments targeting this central signaling pathway in the development of melanoma are promising and new molecules should be developed. NC1(XIX) seems to have the potential for the design of new anti-cancer drugs.
Mots clés
3-Phosphoinositide-Dependent Protein Kinases, metabolism, Antineoplastic Agents, pharmacology, Cell Line, Tumor, Collagen, metabolism, Fibril-Associated Collagens, metabolism, Focal Adhesion Kinase 1, metabolism, Glycogen Synthase Kinase 3 beta, metabolism, Humans, Integrin alphaVbeta3, drug effects, Melanoma, drug therapy, Molecular Targeted Therapy, Peptide Fragments, metabolism, Phosphatidylinositol 3-Kinase, metabolism, Phosphorylation, Protein Domains, Proto-Oncogene Proteins c-akt, metabolism, Signal Transduction, drug effects, Skin Neoplasms, drug therapy, TOR Serine-Threonine Kinases, metabolism
Référence
Oncotarget. 2016 Jan;7(2):1516-28
