Title
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
Content
Details
Object type
PDFDocument
Format
application/pdf
Created
18.09.2023 02:55:04
This object is in collection
Metadata
Veterinärmedizinische Universität Wien (Vetmeduni) | Veterinärplatz 1 | 1210 Wien - Österreich | T +43 1 25077 1414 | Web: vetmeduni.ac.at