Erythropoietin receptor regulates tumor mitochondrial biogenesis through iNOS and pAKT
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 mitochond...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Oncology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.976961/full |
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| author | Mostafa A. Aboouf Mostafa A. Aboouf Mostafa A. Aboouf Mostafa A. Aboouf Franco Guscetti Nadine von Büren Nadine von Büren Julia Armbruster Julia Armbruster Hyrije Ademi Hyrije Ademi Maja Ruetten Florinda Meléndez-Rodríguez Thomas Rülicke Alexander Seymer Robert A. Jacobs Edith M. Schneider Gasser Edith M. Schneider Gasser Julian Aragones Drorit Neumann Max Gassmann Max Gassmann Markus Thiersch Markus Thiersch Markus Thiersch |
| author_facet | Mostafa A. Aboouf Mostafa A. Aboouf Mostafa A. Aboouf Mostafa A. Aboouf Franco Guscetti Nadine von Büren Nadine von Büren Julia Armbruster Julia Armbruster Hyrije Ademi Hyrije Ademi Maja Ruetten Florinda Meléndez-Rodríguez Thomas Rülicke Alexander Seymer Robert A. Jacobs Edith M. Schneider Gasser Edith M. Schneider Gasser Julian Aragones Drorit Neumann Max Gassmann Max Gassmann Markus Thiersch Markus Thiersch Markus Thiersch |
| author_sort | Mostafa A. Aboouf |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T06:17:51Z |
| format | Article |
| id | doaj.art-310af4056b6044878b44d59abc419570 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-12T06:17:51Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-310af4056b6044878b44d59abc4195702022-12-22T03:44:25ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-08-011210.3389/fonc.2022.976961976961Erythropoietin receptor regulates tumor mitochondrial biogenesis through iNOS and pAKTMostafa A. Aboouf0Mostafa A. Aboouf1Mostafa A. Aboouf2Mostafa A. Aboouf3Franco Guscetti4Nadine von Büren5Nadine von Büren6Julia Armbruster7Julia Armbruster8Hyrije Ademi9Hyrije Ademi10Maja Ruetten11Florinda Meléndez-Rodríguez12Thomas Rülicke13Alexander Seymer14Robert A. Jacobs15Edith M. Schneider Gasser16Edith M. Schneider Gasser17Julian Aragones18Drorit Neumann19Max Gassmann20Max Gassmann21Markus Thiersch22Markus Thiersch23Markus Thiersch24Institute of Veterinary Physiology, Vetsuisse Faculty, University of Zurich, Zurich, SwitzerlandZurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Zurich, SwitzerlandCenter for Clinical Studies, Vetsuisse Faculty, University of Zurich, Zurich, SwitzerlandDepartment of Biochemistry, Faculty of Pharmacy, Ain Shams University, Cairo, EgyptInstitute of Veterinary Pathology, Vetsuisse Faculty, University of Zurich, Zurich, SwitzerlandInstitute of Veterinary Physiology, Vetsuisse Faculty, University of Zurich, Zurich, SwitzerlandCenter for Clinical Studies, Vetsuisse Faculty, University of Zurich, Zurich, SwitzerlandInstitute of Veterinary Physiology, Vetsuisse Faculty, University of Zurich, Zurich, SwitzerlandCenter for Clinical Studies, Vetsuisse Faculty, University of Zurich, Zurich, SwitzerlandInstitute of Veterinary Physiology, Vetsuisse Faculty, University of Zurich, Zurich, SwitzerlandCenter for Clinical Studies, Vetsuisse Faculty, University of Zurich, Zurich, SwitzerlandPathoVet AG, Pathology Diagnostic Laboratory, Tagelswangen, SwitzerlandHospital Universitario Santa Cristina, Autonomous University of Madrid, Madrid, SpainDepartment of Biomedical Sciences, University of Veterinary Medicine Vienna, Vienna, AustriaDepartment for Sociology and Social Geography, Paris Lodron University of Salzburg (PLUS), Salzburg, Austria0Department of Human Physiology & Nutrition, University of Colorado Colorado Springs (UCCS), Colorado Springs, CO, United StatesInstitute of Veterinary Physiology, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland1Center of Neuroscience Zurich (ZNZ), University of Zurich, Zurich, SwitzerlandHospital Universitario Santa Cristina, Autonomous University of Madrid, Madrid, Spain2Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel Aviv University, Tel-Aviv, IsraelInstitute of Veterinary Physiology, Vetsuisse Faculty, University of Zurich, Zurich, SwitzerlandZurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Zurich, SwitzerlandInstitute of Veterinary Physiology, Vetsuisse Faculty, University of Zurich, Zurich, SwitzerlandZurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Zurich, SwitzerlandCenter for Clinical Studies, Vetsuisse Faculty, University of Zurich, Zurich, SwitzerlandErythropoietin 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.https://www.frontiersin.org/articles/10.3389/fonc.2022.976961/fullerythropoietin receptortumor metabolismmitochondrial biogenesisnitric oxide (NO)respirometryOXPHOS |
| spellingShingle | Mostafa A. Aboouf Mostafa A. Aboouf Mostafa A. Aboouf Mostafa A. Aboouf Franco Guscetti Nadine von Büren Nadine von Büren Julia Armbruster Julia Armbruster Hyrije Ademi Hyrije Ademi Maja Ruetten Florinda Meléndez-Rodríguez Thomas Rülicke Alexander Seymer Robert A. Jacobs Edith M. Schneider Gasser Edith M. Schneider Gasser Julian Aragones Drorit Neumann Max Gassmann Max Gassmann Markus Thiersch Markus Thiersch Markus Thiersch Erythropoietin receptor regulates tumor mitochondrial biogenesis through iNOS and pAKT Frontiers in Oncology erythropoietin receptor tumor metabolism mitochondrial biogenesis nitric oxide (NO) respirometry OXPHOS |
| title | Erythropoietin receptor regulates tumor mitochondrial biogenesis through iNOS and pAKT |
| title_full | Erythropoietin receptor regulates tumor mitochondrial biogenesis through iNOS and pAKT |
| title_fullStr | Erythropoietin receptor regulates tumor mitochondrial biogenesis through iNOS and pAKT |
| title_full_unstemmed | Erythropoietin receptor regulates tumor mitochondrial biogenesis through iNOS and pAKT |
| title_short | Erythropoietin receptor regulates tumor mitochondrial biogenesis through iNOS and pAKT |
| title_sort | erythropoietin receptor regulates tumor mitochondrial biogenesis through inos and pakt |
| topic | erythropoietin receptor tumor metabolism mitochondrial biogenesis nitric oxide (NO) respirometry OXPHOS |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.976961/full |
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