Tenascin-C orchestrates glioblastoma angiogenesis by modulation of pro- and anti-angiogenic signaling

Abstract: High expression of the extracellular matrix component tenascin-C in the tumor microenvironment correlates with decreased patient survival. Tenascin-C promotes cancer progression and a disrupted tumor vasculature through an unclear mechanism. Here, we examine the angiomodulatory role of tenascin-C. We find that direct contact of endothelial cells with tenascin-C disrupts actin polymerization, resulting in cytoplasmic retention of the transcriptional coactivator YAP. Tenascin-C also downregulates YAP pro-angiogenic target genes, thus reducing endothelial cell survival, proliferation, and tubulogenesis. Glioblastoma cells exposed to tenascin-C secrete pro-angiogenic factors that promote endothelial cell survival and tubulogenesis. Proteomic analysis of their secretome reveals a signature, including ephrin-B2, that predicts decreased survival of glioma patients. We find that ephrin-B2 is an important pro-angiogenic tenascin-C effector. Thus, we demonstrate dual activities for tenascin-C in glioblastoma angiogenesis and uncover potential targeting and prediction opportunities

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• Location: Deutsche Nationalbibliothek Frankfurt am Main
• Extent: Online-Ressource
• Language: Englisch
• Notes: Cell reports. - 17, 10 (2016) , 2607-2619, ISSN: 2211-1247

Contributors, Places and Time

• Event: Veröffentlichung
• (where): Freiburg
• (who): Universität
• (when): 2025
• Creator: Rupp, Tristan ; Langlois, Benoit ; Koczorowska, Maria Magdalena ; Radwanska, Agata ; Sun, Zhen ; Hussenet, Thomas ; Lefebvre, Olivier ; Murdamoothoo, Devadarssen ; Arnold, Christiane ; Klein, Annick ; Biniossek, Martin Lothar ; Hyenne, Vincent ; Naudin, Elise ; Velazquez-Quesada, Ines ; Schilling, Oliver ; Obberghen-Schilling, Ellen van ; Orend, Gertraud
• Contributor: Zentrum für Biochemie und Molekulare Zellforschung

Further information

• DOI: 10.1016/j.celrep.2016.11.012
• URN: urn:nbn:de:bsz:25-freidok-1352478
• Rights: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.