title: The anti-tumor NC1 domain of collagen XIX inhibits the FAK/ PI3K/Akt/mTOR signaling pathway through αvβ3 integrin interaction.
abstract: 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.
authors.affiliation: Université de Reims Champagne-Ardenne, CNRS UMR 7369 (Matrice Extracellulaire et Dynamique Cellulaire, MEDyC), Reims, France.|CHU de Reims, Laboratoire Central de Biochimie, Reims, France.
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Oudart
authors.affiliation: Université de Reims Champagne-Ardenne, CNRS UMR 7369 (Matrice Extracellulaire et Dynamique Cellulaire, MEDyC), Reims, France.
authors.forename: Manon
authors.initials: M
authors.lastname: Doué
authors.affiliation: Université de Reims Champagne-Ardenne, CNRS UMR 7369 (Matrice Extracellulaire et Dynamique Cellulaire, MEDyC), Reims, France.
authors.forename: Alexia
authors.initials: A
authors.lastname: Vautrin
authors.affiliation: Université de Reims Champagne-Ardenne, CNRS UMR 7369 (Matrice Extracellulaire et Dynamique Cellulaire, MEDyC), Reims, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Brassart
authors.affiliation: Université de Reims Champagne-Ardenne, CNRS UMR 7369 (Matrice Extracellulaire et Dynamique Cellulaire, MEDyC), Reims, France.
authors.forename: Christèle
authors.initials: C
authors.lastname: Sellier
authors.affiliation: Université de Reims Champagne-Ardenne, CNRS UMR 7369 (Matrice Extracellulaire et Dynamique Cellulaire, MEDyC), Reims, France.
authors.forename: Aurelie
authors.initials: A
authors.lastname: Dupont-Deshorgue
authors.affiliation: Université de Reims Champagne-Ardenne, CNRS UMR 7369 (Matrice Extracellulaire et Dynamique Cellulaire, MEDyC), Reims, France.|CHU de Reims, Laboratoire Central de Biochimie, Reims, France.
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Monboisse
authors.affiliation: Université de Reims Champagne-Ardenne, CNRS UMR 7369 (Matrice Extracellulaire et Dynamique Cellulaire, MEDyC), Reims, France.|CHU de Reims, Laboratoire Central de Biochimie, Reims, France.
authors.forename: François-Xavier
authors.initials: FX
authors.lastname: Maquart
authors.affiliation: Université de Reims Champagne-Ardenne, CNRS UMR 7369 (Matrice Extracellulaire et Dynamique Cellulaire, MEDyC), Reims, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Brassart-Pasco
authors.affiliation: Université de Reims Champagne-Ardenne, CNRS UMR 7369 (Matrice Extracellulaire et Dynamique Cellulaire, MEDyC), Reims, France.|CHU de Reims, Laboratoire Central de Biochimie, Reims, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Ramont
mesh_terms: D064413:3-Phosphoinositide-Dependent Protein Kinases / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D003094:Collagen / Q000378:metabolism* / Q000494:pharmacology; D024021:Fibril-Associated Collagens / Q000378:metabolism* / Q000494:pharmacology; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta / Q000378:metabolism; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000187:drug effects / Q000378:metabolism*; D008545:Melanoma / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D058990:Molecular Targeted Therapy; D010446:Peptide Fragments / Q000378:metabolism* / Q000494:pharmacology; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D010766:Phosphorylation; D000072417:Protein Domains; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D012878:Skin Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D024021:Fibril-Associated Collagens; D039302:Integrin alphaVbeta3; D010446:Peptide Fragments; C000612264:collagen XIX protein, human; D003094:Collagen; C546842:MTOR protein, human; D058539:Phosphatidylinositol 3-Kinase; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D064413:3-Phosphoinositide-Dependent Protein Kinases; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; C578562:PDPK1 protein, human; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases
keywords: FAK/PI3K/Akt/mTOR; NC1 domain; collagen XIX; integrin; tumor invasion