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c‐MYB‐ and PGC1a‐dependent metabolic switch induced by MYBBP1A loss in renal cancer
The tumor microenvironment may alter the original tumorigenic potential of tumor cells. Under harsh environmental conditions, genetic alterations conferring selective advantages may initiate the growth of tumor subclones, providing new opportunities for these tumors to grow. We performed a genetic l...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6599841/ https://www.ncbi.nlm.nih.gov/pubmed/31066170 http://dx.doi.org/10.1002/1878-0261.12499 |
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author | Felipe‐Abrio, Blanca Verdugo‐Sivianes, Eva M. Carnero, Amancio |
author_facet | Felipe‐Abrio, Blanca Verdugo‐Sivianes, Eva M. Carnero, Amancio |
author_sort | Felipe‐Abrio, Blanca |
collection | PubMed |
description | The tumor microenvironment may alter the original tumorigenic potential of tumor cells. Under harsh environmental conditions, genetic alterations conferring selective advantages may initiate the growth of tumor subclones, providing new opportunities for these tumors to grow. We performed a genetic loss‐of‐function screen to identify genetic alterations able to promote tumor cell growth in the absence of glucose. We identified that downregulation of MYBBP1A increases tumorigenic properties under nonpermissive conditions. MYBBP1A downregulation simultaneously activates PGC1α, directly by alleviating direct repression and indirectly by increasing PGC1α mRNA levels through c‐MYB, leading to a metabolic switch from glycolysis to OXPHOS and increased tumorigenesis in low‐glucose microenvironments. We have also identified reduced MYBBP1A expression in human renal tumor samples, which show high expression levels of genes involved in oxidative metabolism. In summary, our data support the role of MYBBP1A as a tumor suppressor by regulating c‐MYB and PGC1α. Therefore, loss of MYBBP1A increases adaptability spanning of tumors through metabolic switch. |
format | Online Article Text |
id | pubmed-6599841 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-65998412019-07-22 c‐MYB‐ and PGC1a‐dependent metabolic switch induced by MYBBP1A loss in renal cancer Felipe‐Abrio, Blanca Verdugo‐Sivianes, Eva M. Carnero, Amancio Mol Oncol Research Articles The tumor microenvironment may alter the original tumorigenic potential of tumor cells. Under harsh environmental conditions, genetic alterations conferring selective advantages may initiate the growth of tumor subclones, providing new opportunities for these tumors to grow. We performed a genetic loss‐of‐function screen to identify genetic alterations able to promote tumor cell growth in the absence of glucose. We identified that downregulation of MYBBP1A increases tumorigenic properties under nonpermissive conditions. MYBBP1A downregulation simultaneously activates PGC1α, directly by alleviating direct repression and indirectly by increasing PGC1α mRNA levels through c‐MYB, leading to a metabolic switch from glycolysis to OXPHOS and increased tumorigenesis in low‐glucose microenvironments. We have also identified reduced MYBBP1A expression in human renal tumor samples, which show high expression levels of genes involved in oxidative metabolism. In summary, our data support the role of MYBBP1A as a tumor suppressor by regulating c‐MYB and PGC1α. Therefore, loss of MYBBP1A increases adaptability spanning of tumors through metabolic switch. John Wiley and Sons Inc. 2019-06-11 2019-07 /pmc/articles/PMC6599841/ /pubmed/31066170 http://dx.doi.org/10.1002/1878-0261.12499 Text en © 2019 The Authors. Published by FEBS Press and John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Felipe‐Abrio, Blanca Verdugo‐Sivianes, Eva M. Carnero, Amancio c‐MYB‐ and PGC1a‐dependent metabolic switch induced by MYBBP1A loss in renal cancer |
title | c‐MYB‐ and PGC1a‐dependent metabolic switch induced by MYBBP1A loss in renal cancer |
title_full | c‐MYB‐ and PGC1a‐dependent metabolic switch induced by MYBBP1A loss in renal cancer |
title_fullStr | c‐MYB‐ and PGC1a‐dependent metabolic switch induced by MYBBP1A loss in renal cancer |
title_full_unstemmed | c‐MYB‐ and PGC1a‐dependent metabolic switch induced by MYBBP1A loss in renal cancer |
title_short | c‐MYB‐ and PGC1a‐dependent metabolic switch induced by MYBBP1A loss in renal cancer |
title_sort | c‐myb‐ and pgc1a‐dependent metabolic switch induced by mybbp1a loss in renal cancer |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6599841/ https://www.ncbi.nlm.nih.gov/pubmed/31066170 http://dx.doi.org/10.1002/1878-0261.12499 |
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