Tenascin-C downregulates wnt inhibitor dickkopf-1, promoting tumorigenesis in a neuroendocrine tumor model.
Fiche publication
Date publication
octobre 2013
Auteurs
Membres identifiés du Cancéropôle Est :
Dr LANGLOIS Benoît, Dr LEFEBVRE Olivier, Dr OREND Gertraud
Tous les auteurs :
Saupe F, Schwenzer A, Jia Y, Gasser I, Spenle C, Langlois B, Kammerer M, Lefebvre O, Hlushchuk R, Rupp T, Marko M, van der Heyden M, Cremel G, Arnold C, Klein A, Simon-Assmann P, Djonov V, Neuville-Mechine A, Esposito I, Slotta-Huspenina J, Janssen KP, de Wever O, Christofori G, Hussenet T, Orend G
Lien Pubmed
Résumé
The extracellular matrix molecule tenascin-C (TNC) is a major component of the cancer-specific matrix, and high TNC expression is linked to poor prognosis in several cancers. To provide a comprehensive understanding of TNC's functions in cancer, we established an immune-competent transgenic mouse model of pancreatic beta-cell carcinogenesis with varying levels of TNC expression and compared stochastic neuroendocrine tumor formation in abundance or absence of TNC. We show that TNC promotes tumor cell survival, the angiogenic switch, more and leaky vessels, carcinoma progression, and lung micrometastasis. TNC downregulates Dickkopf-1 (DKK1) promoter activity through the blocking of actin stress fiber formation, activates Wnt signaling, and induces Wnt target genes in tumor and endothelial cells. Our results implicate DKK1 downregulation as an important mechanism underlying TNC-enhanced tumor progression through the provision of a proangiogenic tumor microenvironment.
Référence
Cell Rep. 2013 Oct 31;5(2):482-92