Title (en)
Erythropoietin receptor regulates tumor mitochondrial biogenesis through iNOS and pAKT
Language
English
Description (en)
Erythropoietin receptor (EPOR) is widely expressed in healthy and malignant tissues. In certain malignancies, EPOR stimulates tumor growth. In healthy tissues, EPOR controls processes other than erythropoiesis, including mitochondrial metabolism. We hypothesized that EPOR also controls the mitochondrial metabolism in cancer cells. To test this hypothesis, we generated EPOR-knockdown cancer cells to grow tumor xenografts in mice and analyzed tumor cellular respiration via high-resolution respirometry. Furthermore, we analyzed cellular respiratory control, mitochondrial content, and regulators of mitochondrial biogenesis in vivo and in vitro in different cancer cell lines. Our results show that EPOR controls tumor growth and mitochondrial biogenesis in tumors by controlling the levels of both, pAKT and inducible NO synthase (iNOS). Furthermore, we observed that the expression of EPOR is associated with the expression of the mitochondrial marker VDAC1 in tissue arrays of lung cancer patients, suggesting that EPOR indeed helps to regulate mitochondrial biogenesis in tumors of cancer patients. Thus, our data imply that EPOR not only stimulates tumor growth but also regulates tumor metabolism and is a target for direct intervention against progression.
Keywords (en)
Nitric-Oxide; Skeletal-Muscle; Gene-Expression; Survival; Growth; Cells; Proliferation; Transcription; Pgc-1-Alpha; Metabolism
DOI
10.3389/fonc.2022.976961
Author of the digital object
Mostafa A. Aboouf (University of Zurich / Ain Shams University)
Markus Thiersch (University of Zurich)
Max Gassmann (University of Zurich)
Drorit Neumann (Tel Aviv University)
Julian Aragones (Autonomous University of Madrid)
Edith M. Schneider Gasser (University of Zurich)
Robert A. Jacobs (University of Colorado Colorado Springs)
Thomas Rülicke (University of Veterinary Medicine Vienna)
Alexander Seymer (Paris Lodron University of Salzburg)
Florinda Meléndez-Rodríguez (Autonomous University of Madrid)
Maja Ruetten (PathoVet AG)
Hyrije Ademi (University of Zurich)
Julia Armbruster (University of Zurich)
Franco Guscetti (University of Zurich)
Nadine von Büren (University of Zurich)
Format
application/pdf
Size
8.2 MB
Licence Selected
CC BY 4.0 International
Type of publication
Article
Name of Publication (en)
Frontiers in Oncology
Pages or Volume
16
Volume
12
Publisher
Frontiers Media Sa
Publication Date
2022
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Persistent identifier
DOI
https://phaidra.vetmeduni.ac.at/o:2107
https://doi.org/10.3389/fonc.2022.976961 - Content
- DetailsObject typePDFDocumentFormatapplication/pdfCreated18.09.2023 02:55:04
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