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| Verfasst von: | Cangkrama, Michael [VerfasserIn]  |
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| | Wietecha, Mateusz [VerfasserIn] |
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| | Mathis, Nicolas [VerfasserIn] |
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| | Okumura, Rin [VerfasserIn] |
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| | Ferrarese, Luca [VerfasserIn] |
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| | Al-Nuaimi, Dunja [VerfasserIn] |
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| | Antsiferova, Maria [VerfasserIn] |
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| | Dummer, Reinhard [VerfasserIn] |
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| | Innocenti, Metello [VerfasserIn] |
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| | Werner, Sabine [VerfasserIn] |
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| Titel: | A paracrine activin A-mDia2 axis promotes squamous carcinogenesis via fibroblast reprogramming |
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| Verf.angabe: | Michael Cangkrama, Mateusz Wietecha, Nicolas Mathis, Rin Okumura, Luca Ferrarese, Dunja Al-Nuaimi, Maria Antsiferova, Reinhard Dummer, Metello Innocenti, Sabine Werner |
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| E-Jahr: | 2020 |
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| Jahr: | 9 March 2020 |
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| Fussnoten: | Gesehen am 07.01.2021 |
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| Titel Quelle: | Enthalten in: European Molecular Biology OrganizationEMBO molecular medicine |
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| Ort Quelle: | [London] : Nature Publishing Group UK, 2009 |
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| Jahr Quelle: | 2020 |
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| Band/Heft Quelle: | 12(2020,4) Artikel-Nummer e11466, 21 Seiten |
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| ISSN Quelle: | 1757-4684 |
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| Abstract: | Abstract Cancer-associated fibroblasts (CAFs) are key regulators of tumorigenesis and promising targets for next-generation therapies. We discovered that cancer cell-derived activin A reprograms fibroblasts into pro-tumorigenic CAFs. Mechanistically, this occurs via Smad2-mediated transcriptional regulation of the formin mDia2, which directly promotes filopodia formation and cell migration. mDia2 also induces expression of CAF marker genes through prevention of p53 nuclear accumulation, resulting in the production of a pro-tumorigenic matrisome and secretome. The translational relevance of this finding is reflected by activin A overexpression in tumor cells and of mDia2 in the stroma of skin cancer and other malignancies and the correlation of high activin A/mDia2 levels with poor patient survival. Blockade of this signaling axis using inhibitors of activin, activin receptors, or mDia2 suppressed cancer cell malignancy and squamous carcinogenesis in 3D organotypic cultures, ex vivo, and in vivo, providing a rationale for pharmacological inhibition of activin A-mDia2 signaling in stratified cancer patients. |
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| DOI: | doi:10.15252/emmm.201911466 |
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| URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
Volltext: https://doi.org/10.15252/emmm.201911466 |
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| | Volltext: https://www.embopress.org/doi/full/10.15252/emmm.201911466 |
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| | DOI: https://doi.org/10.15252/emmm.201911466 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| Sach-SW: | activin |
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| | CAF |
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| | carcinogenesis |
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| | mDia2 |
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| | tumor microenvironment |
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| K10plus-PPN: | 1744178305 |
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| Verknüpfungen: | → Zeitschrift |
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¬A¬ paracrine activin A-mDia2 axis promotes squamous carcinogenesis via fibroblast reprogramming / Cangkrama, Michael [VerfasserIn]; 9 March 2020 (Online-Ressource)
