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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 β-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.

Original publication




Journal article


Cell reports

Publication Date





482 - 492


Inserm U1109, MN3T Team, The Microenvironmental Niche in Tumorigenesis and Targeted Therapy, 3 Avenue Molière, 67200 Strasbourg, France; Université de Strasbourg, 67000 Strasbourg, France; LabEx Medalis, Université de Strasbourg, 67000 Strasbourg, France; Fédération de Médecine Translationnelle de Strasbourg (FMTS), 67000 Strasbourg, France.


Cell Line, Tumor, Animals, Mice, Inbred C57BL, Mice, Knockout, Humans, Mice, Neuroendocrine Tumors, Cell Transformation, Neoplastic, Disease Models, Animal, Neovascularization, Pathologic, Intercellular Signaling Peptides and Proteins, Tenascin, Signal Transduction, Down-Regulation, Wnt Proteins, Human Umbilical Vein Endothelial Cells