| |  Online-Ressource |
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| Verfasst von: | Imkeller, Katharina [VerfasserIn]  |
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| | Ambrosi, Giulia [VerfasserIn] |
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| | Klemm, Nancy [VerfasserIn] |
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| | Henkel, Luisa [VerfasserIn] |
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| | Huber, Wolfgang [VerfasserIn] |
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| | Boutros, Michael [VerfasserIn] |
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| Titel: | Metabolic balance in colorectal cancer is maintained by optimal Wnt signaling levels |
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| Mitwirkende: | Claveras Cabezudo, Ainara |
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| Verf.angabe: | Katharina Imkeller, Giulia Ambrosi, Nancy Klemm, Ainara Claveras Cabezudo, Luisa Henkel, Wolfgang Huber & Michael Boutros |
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| E-Jahr: | 2022 |
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| Jahr: | 29 July 2022 |
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| Umfang: | 18 S. |
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| Fussnoten: | Gesehen am 05.09.2022 |
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| Titel Quelle: | Enthalten in: Molecular systems biology |
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| Ort Quelle: | Heidelberg : EMBO Press, 2005 |
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| Jahr Quelle: | 2022 |
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| Band/Heft Quelle: | 18(2022), 8, Artikel-ID e10874, Seite 1-18 |
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| ISSN Quelle: | 1744-4292 |
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| Abstract: | Abstract Wnt pathways are important for the modulation of tissue homeostasis, and their deregulation is linked to cancer development. Canonical Wnt signaling is hyperactivated in many human colorectal cancers due to genetic alterations of the negative Wnt regulator APC. However, the expression levels of Wnt-dependent targets vary between tumors, and the mechanisms of carcinogenesis concomitant with this Wnt signaling dosage have not been understood. In this study, we integrate whole-genome CRISPR/Cas9 screens with large-scale multi-omic data to delineate functional subtypes of cancer. We engineer APC loss-of-function mutations and thereby hyperactivate Wnt signaling in cells with low endogenous Wnt activity and find that the resulting engineered cells have an unfavorable metabolic equilibrium compared with cells which naturally acquired Wnt hyperactivation. We show that the dosage level of oncogenic Wnt hyperactivation impacts the metabolic equilibrium and the mitochondrial phenotype of a given cell type in a context-dependent manner. These findings illustrate the impact of context-dependent genetic interactions on cellular phenotypes of a central cancer driver mutation and expand our understanding of quantitative modulation of oncogenic signaling in tumorigenesis. |
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| DOI: | doi:10.15252/msb.202110874 |
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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.
kostenfrei: Volltext ; Verlag: https://doi.org/10.15252/msb.202110874 |
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| | kostenfrei: Volltext: https://www.embopress.org/doi/full/10.15252/msb.202110874 |
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| | DOI: https://doi.org/10.15252/msb.202110874 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| Sach-SW: | APC |
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| | functional genomics |
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| | multi-omic data integration |
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| | quantitative signaling |
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| | synthetic lethality |
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| K10plus-PPN: | 1815794429 |
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| Verknüpfungen: | → Zeitschrift |
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Metabolic balance in colorectal cancer is maintained by optimal Wnt signaling levels / Imkeller, Katharina [VerfasserIn]; 29 July 2022 (Online-Ressource)
