Title (eng)

Erythropoietin receptor regulates tumor mitochondrial biogenesis through iNOS and pAKT

Author

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

Publishing

Frontiers Media Sa

Description (eng)

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.

Object languages

English

Date

2022

Rights

This work is licensed under a
CC BY 4.0 - Creative Commons Attribution 4.0 International License.

CC BY 4.0 International

http://creativecommons.org/licenses/by/4.0/

Classification

Nitric-Oxide; Skeletal-Muscle; Gene-Expression; Survival; Growth; Cells; Proliferation; Transcription; Pgc-1-Alpha; Metabolism

Member of the Collection(s) (1)