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Increased lactate dehydrogenase activity is dispensable in squamous carcinoma cells of origin

Although numerous therapeutic strategies have attempted to target aerobic glycolysis to inhibit tumor progression, these approaches have not resulted in effective clinical outcomes. Murine squamous cell carcinoma (SCC) can be initiated by hair follicle stem cells (HFSCs). HFSCs utilize aerobic glyco...

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Autores principales: Flores, A., Sandoval-Gonzalez, S., Takahashi, R., Krall, A., Sathe, L., Wei, L., Radu, C., Joly, J. H., Graham, N. A., Christofk, H. R., Lowry, W. E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6327029/
https://www.ncbi.nlm.nih.gov/pubmed/30626875
http://dx.doi.org/10.1038/s41467-018-07857-9
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author Flores, A.
Sandoval-Gonzalez, S.
Takahashi, R.
Krall, A.
Sathe, L.
Wei, L.
Radu, C.
Joly, J. H.
Graham, N. A.
Christofk, H. R.
Lowry, W. E.
author_facet Flores, A.
Sandoval-Gonzalez, S.
Takahashi, R.
Krall, A.
Sathe, L.
Wei, L.
Radu, C.
Joly, J. H.
Graham, N. A.
Christofk, H. R.
Lowry, W. E.
author_sort Flores, A.
collection PubMed
description Although numerous therapeutic strategies have attempted to target aerobic glycolysis to inhibit tumor progression, these approaches have not resulted in effective clinical outcomes. Murine squamous cell carcinoma (SCC) can be initiated by hair follicle stem cells (HFSCs). HFSCs utilize aerobic glycolysis, and the activity of lactate dehydrogenase (Ldh) is essential for HFSC activation. We sought to determine whether Ldh activity in SCC is critical for tumorigenesis or simply a marker of the cell type of origin. Genetic abrogation or induction of Ldh activity in HFSC-mediated tumorigenesis shows no effect on tumorigenesis as measured by number, time to formation, proliferation, volume, epithelial to mesenchymal transition, gene expression, or immune response. Ldha-null tumors show dramatically reduced levels of glycolytic metabolites by metabolomics, and significantly reduced glucose uptake by FDG-PET live animal imaging. These results suggest that squamous cancer cells of origin do not require increased glycolytic activity to generate cancers.
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spelling pubmed-63270292019-03-28 Increased lactate dehydrogenase activity is dispensable in squamous carcinoma cells of origin Flores, A. Sandoval-Gonzalez, S. Takahashi, R. Krall, A. Sathe, L. Wei, L. Radu, C. Joly, J. H. Graham, N. A. Christofk, H. R. Lowry, W. E. Nat Commun Article Although numerous therapeutic strategies have attempted to target aerobic glycolysis to inhibit tumor progression, these approaches have not resulted in effective clinical outcomes. Murine squamous cell carcinoma (SCC) can be initiated by hair follicle stem cells (HFSCs). HFSCs utilize aerobic glycolysis, and the activity of lactate dehydrogenase (Ldh) is essential for HFSC activation. We sought to determine whether Ldh activity in SCC is critical for tumorigenesis or simply a marker of the cell type of origin. Genetic abrogation or induction of Ldh activity in HFSC-mediated tumorigenesis shows no effect on tumorigenesis as measured by number, time to formation, proliferation, volume, epithelial to mesenchymal transition, gene expression, or immune response. Ldha-null tumors show dramatically reduced levels of glycolytic metabolites by metabolomics, and significantly reduced glucose uptake by FDG-PET live animal imaging. These results suggest that squamous cancer cells of origin do not require increased glycolytic activity to generate cancers. Nature Publishing Group UK 2019-01-09 /pmc/articles/PMC6327029/ /pubmed/30626875 http://dx.doi.org/10.1038/s41467-018-07857-9 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Flores, A.
Sandoval-Gonzalez, S.
Takahashi, R.
Krall, A.
Sathe, L.
Wei, L.
Radu, C.
Joly, J. H.
Graham, N. A.
Christofk, H. R.
Lowry, W. E.
Increased lactate dehydrogenase activity is dispensable in squamous carcinoma cells of origin
title Increased lactate dehydrogenase activity is dispensable in squamous carcinoma cells of origin
title_full Increased lactate dehydrogenase activity is dispensable in squamous carcinoma cells of origin
title_fullStr Increased lactate dehydrogenase activity is dispensable in squamous carcinoma cells of origin
title_full_unstemmed Increased lactate dehydrogenase activity is dispensable in squamous carcinoma cells of origin
title_short Increased lactate dehydrogenase activity is dispensable in squamous carcinoma cells of origin
title_sort increased lactate dehydrogenase activity is dispensable in squamous carcinoma cells of origin
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6327029/
https://www.ncbi.nlm.nih.gov/pubmed/30626875
http://dx.doi.org/10.1038/s41467-018-07857-9
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