| |  Online-Ressource |
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| Verfasst von: | Radić Shechter, Ksenija [VerfasserIn]  |
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| | Kafkia, Eleni [VerfasserIn] |
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| | Zirngibl, Katharina [VerfasserIn] |
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| | Gawrzak, Sylwia [VerfasserIn] |
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| | Alladin, Ashna [VerfasserIn] |
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| | Machado, Daniel [VerfasserIn] |
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| | Lüchtenborg, Christian [VerfasserIn] |
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| | Sévin, Daniel Charles [VerfasserIn] |
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| | Brügger, Britta [VerfasserIn] |
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| | Patil, Kiran Raosaheb [VerfasserIn] |
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| | Jechlinger, Martin [VerfasserIn] |
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| Titel: | Metabolic memory underlying minimal residual disease in breast cancer |
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| Verf.angabe: | Ksenija Radic Shechter, Eleni Kafkia, Katharina Zirngibl, Sylwia Gawrzak, Ashna Alladin, Daniel Machado, Christian Luechtenborg, Daniel C. Sevin, Britta Bruegger, Kiran R. Patil and Martin Jechlinger |
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| E-Jahr: | 2021 |
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| Jahr: | 29 September 2021 |
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| Umfang: | 21 S. |
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| Fussnoten: | Gesehen am 28.01.2022 |
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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: | 2021 |
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| Band/Heft Quelle: | 17(2021), 10, Artikel-ID e10141, Seite 1-21 |
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| ISSN Quelle: | 1744-4292 |
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| Abstract: | Tumor relapse from treatment-resistant cells (minimal residual disease, MRD) underlies most breast cancer-related deaths. Yet, the molecular characteristics defining their malignancy have largely remained elusive. Here, we integrated multi-omics data from a tractable organoid system with a metabolic modeling approach to uncover the metabolic and regulatory idiosyncrasies of the MRD. We find that the resistant cells, despite their non-proliferative phenotype and the absence of oncogenic signaling, feature increased glycolysis and activity of certain urea cycle enzyme reminiscent of the tumor. This metabolic distinctiveness was also evident in a mouse model and in transcriptomic data from patients following neo-adjuvant therapy. We further identified a marked similarity in DNA methylation profiles between tumor and residual cells. Taken together, our data reveal a metabolic and epigenetic memory of the treatment-resistant cells. We further demonstrate that the memorized elevated glycolysis in MRD is crucial for their survival and can be targeted using a small-molecule inhibitor without impacting normal cells. The metabolic aberrances of MRD thus offer new therapeutic opportunities for post-treatment care to prevent breast tumor recurrence. |
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| DOI: | doi:10.15252/msb.202010141 |
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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 ; Verlag: https://doi.org/10.15252/msb.202010141 |
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| | Volltext: https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=DOISource&SrcApp=WOS&KeyAID=10.15252%2Fmsb.20 ... |
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| | DOI: https://doi.org/10.15252/msb.202010141 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| Sach-SW: | activation |
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| | cells |
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| | dysfunction |
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| | fumarate |
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| | gene-expression |
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| | glycolysis |
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| | inhibition |
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| | metabolic modeling |
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| | multi-omics integration |
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| | mutations |
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| | oncogenic memory |
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| | organoids |
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| | recurrence |
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| | succinate |
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| | therapy |
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| K10plus-PPN: | 1787466124 |
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| Verknüpfungen: | → Zeitschrift |
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Metabolic memory underlying minimal residual disease in breast cancer / Radić Shechter, Ksenija [VerfasserIn]; 29 September 2021 (Online-Ressource)
