Details

Autor(en) / Beteiligte

• Saupe, Falk
• Schwenzer, Anja
• Jia, Yundan
• Gasser, Isabelle
• Spenlé, Caroline
• Langlois, Benoit
• Kammerer, Martial
• Lefebvre, Olivier
• Hlushchuk, Ruslan
• Rupp, Tristan
• Marko, Marija
• van der Heyden, Michael
• Cremel, Gérard
• Arnold, Christiane
• Klein, Annick
• Simon-Assmann, Patricia
• Djonov, Valentin
• Neuville-Méchine, Agnès
• Esposito, Irene
• Slotta-Huspenina, Julia
• Janssen, Klaus-Peter
• de Wever, Olivier
• Christofori, Gerhard
• Hussenet, Thomas
• Orend, Gertraud

Titel

Tenascin-C Downregulates Wnt Inhibitor Dickkopf-1, Promoting Tumorigenesis in a Neuroendocrine Tumor Model

Ist Teil von

• Cell reports (Cambridge), 2013-10, Vol.5 (2), p.482-492

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2013

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• 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. [Display omitted] •An immune competent, stochastic tumor model with high tenascin-C (TNC) is provided•TNC has a decisive role in tumorigenesis by promoting early and late events•TNC downregulates DKK1 expression through disruption of actin stress fibers•TNC transgenic tumor mice are a model for human insulinoma and TNC targeting Orend, Hussenet, and colleagues have established a transgenic immune-competent tumor mouse model that mimics the high expression of TNC observed in human cancer. They show that TNC promotes early and late events such as tumor cell survival, invasion, tumor angiogenesis, and lung metastasis. These phenotypes are linked the to creation of a proangiogenic tumor microenvironment via DKK1 downregulation. Finally, DKK1 expression is dependent on actin stress fibers that are disrupted by TNC.