| |  Online-Ressource |
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| Verfasst von: | Meier, Julia K. [VerfasserIn]  |
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| | Schnetz, Matthias [VerfasserIn] |
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| | Beck, Susanne [VerfasserIn] |
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| | Schmid, Tobias [VerfasserIn] |
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| | Dominguez, Monica [VerfasserIn] |
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| | Kalinovic, Sanela [VerfasserIn] |
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| | Daiber, Andreas [VerfasserIn] |
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| | Brüne, Bernhard [VerfasserIn] |
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| | Jung, Michaela [VerfasserIn] |
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| Titel: | Iron-bound lipocalin-2 protects renal cell carcinoma from ferroptosis |
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| Verf.angabe: | Julia K. Meier, Matthias Schnetz, Susanne Beck, Tobias Schmid, Monica Dominguez, Sanela Kalinovic, Andreas Daiber, Bernhard Brüne and Michaela Jung |
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| E-Jahr: | 2021 |
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| Jahr: | 19 May 2021 |
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| Umfang: | 21 S. |
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| Teil: | volume:11 |
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| | year:2021 |
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| | number:5 |
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| | elocationid:329 |
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| | pages:1-21 |
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| | extent:21 |
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| Fussnoten: | Gesehen am 28.06.2021 |
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| Titel Quelle: | Enthalten in: Metabolites |
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| Ort Quelle: | Basel : MDPI, 2011 |
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| Jahr Quelle: | 2021 |
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| Band/Heft Quelle: | 11(2021), 5, Artikel-ID 329, Seite 1-21 |
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| ISSN Quelle: | 2218-1989 |
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| Abstract: | While the importance of the iron-load of lipocalin-2 (Lcn-2) in promoting tumor progression is widely appreciated, underlying molecular mechanisms largely remain elusive. Considering its role as an iron-transporter, we aimed at clarifying iron-loaded, holo-Lcn-2 (hLcn-2)-dependent signaling pathways in affecting renal cancer cell viability. Applying RNA sequencing analysis in renal CAKI1 tumor cells to explore highly upregulated molecular signatures in response to hLcn-2, we identified a cluster of genes (SLC7A11, GCLM, GLS), which are implicated in regulating ferroptosis. Indeed, hLcn-2-stimulated cells are protected from erastin-induced ferroptosis. We also noticed a rapid increase in reactive oxygen species (ROS) with subsequent activation of the antioxidant Nrf2 pathway. However, knocking down Nrf2 by siRNA was not sufficient to induce erastin-dependent ferroptotic cell death in hLcn-2-stimulated tumor cells. In contrast, preventing oxidative stress through N-acetyl-l-cysteine (NAC) supplementation was still able to induce erastin-dependent ferroptotic cell death in hLcn-2-stimulated tumor cells. Besides an oxidative stress response, we noticed activation of the integrated stress response (ISR), shown by enhanced phosphorylation of eIF-2α and induction of ATF4 after hLcn-2 addition. ATF4 knockdown as well as inhibition of the ISR sensitized hLcn-2-treated renal tumor cells to ferroptosis, thus linking the ISR to pro-tumor characteristics of hLcn-2. Our study provides mechanistic details to better understand tumor pro-survival pathways initiated by iron-loaded Lcn-2. |
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| DOI: | doi:10.3390/metabo11050329 |
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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/10.3390/metabo11050329 |
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| | Volltext: https://www.mdpi.com/2218-1989/11/5/329 |
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| | DOI: https://doi.org/10.3390/metabo11050329 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| Sach-SW: | <i>Nrf2</i> |
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| | <i>SLC7A11</i> |
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| | erastin |
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| | ferroptosis |
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| | iron |
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| | ISR |
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| | lipocalin-2 |
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| | p-eIF2α |
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| | ROS |
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| K10plus-PPN: | 1761321463 |
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| Verknüpfungen: | → Zeitschrift |
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Iron-bound lipocalin-2 protects renal cell carcinoma from ferroptosis / Meier, Julia K. [VerfasserIn]; 19 May 2021 (Online-Ressource)
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