Tenascin-C Promotes Tumor Cell Migration and Metastasis through Integrin α9β1-Mediated YAP Inhibition.
Fiche publication
Date publication
février 2018
Journal
Cancer research
Auteurs
Membres identifiés du Cancéropôle Est :
Dr LEFEBVRE Olivier, Dr OREND Gertraud
Tous les auteurs :
Sun Z, Schwenzer A, Rupp T, Murdamoothoo D, Vegliante R, Lefebvre O, Klein A, Hussenet T, Orend G
Lien Pubmed
Résumé
Tenascin-C is an extracellular matrix molecule that drives progression of many types of human cancer, but the basis for its actions remains obscure. In this study, we describe a cell-autonomous signaling mechanism explaining how tenascin-C promotes cancer cell migration in the tumor microenvironment. In a murine xenograft model of advanced human osteosarcoma, tenascin-C and its receptor integrin α9β1 were determined to be essential for lung metastasis of tumor cells. We determined that activation of this pathway also reduced tumor cell-autonomous expression of target genes for the transcription factor YAP. In clinical specimens, a genetic signature comprising four YAP target genes represents prognostic impact. Taken together, our results illuminate how tumor cell deposition of tenascin-C in the tumor microenvironment promotes invasive migration and metastatic progression. These results illuminate how the extracellular matrix glycoprotein tenascin-C in the tumor microenvironment promotes invasive migration and metastatic progression by employing integrin α9β1, abolishing actin stress fiber formation, inhibiting YAP and its target gene expression, with potential implications for cancer prognosis and therapy. .
Mots clés
Adaptor Proteins, Signal Transducing, antagonists & inhibitors, Animals, Bone Neoplasms, genetics, Cell Line, Tumor, Cell Movement, physiology, Cell Proliferation, physiology, Heterografts, Humans, Integrins, genetics, Mice, Mice, Nude, Neoplasm Metastasis, Osteosarcoma, genetics, Phosphoproteins, antagonists & inhibitors, Signal Transduction, Tenascin, genetics, Transfection, Tumor Microenvironment
Référence
Cancer Res.. 2018 Feb 15;78(4):950-961