Tenascin-C downregulates wnt inhibitor dickkopf-1, promoting tumorigenesis in a neuroendocrine tumor model

Saupe, F. and Schwenzer, A. and Jia, Y. and Gasser, I. and Spenle, C. and Langlois, B. and Kammerer, M. and Lefebvre, O. and Hlushchuk, R. and Rupp, T. and Marko, M. and van der Heyden, M. and Cremel, G. and Arnold, C. and Klein, A. and Simon-Assmann, P. and Djonov, V. and Neuville-Mechine, A. and Esposito, I. and Slotta-Huspenina, J. and Janssen, K. P. and de Wever, O. and Christofori, G. and Hussenet, T. and Orend, G.. (2013) Tenascin-C downregulates wnt inhibitor dickkopf-1, promoting tumorigenesis in a neuroendocrine tumor model. Cell reports, Vol. 5, H. 2. S. 482-492.

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Official URL: http://edoc.unibas.ch/dok/A6338672

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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.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Division of Biochemistry and Genetics > Tumor Biology (Christofori)
UniBasel Contributors:Christofori, Gerhard M.
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:10 Apr 2015 09:13
Deposited On:10 Apr 2015 09:13

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