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Glycolysis is the primary bioenergetic pathway for cell motility and cytoskeletal remodeling in human prostate and breast cancer cells

The ability of a cancer cell to detach from the primary tumor and move to distant sites is fundamental to a lethal cancer phenotype. Metabolic transformations are associated with highly motile aggressive cellular phenotypes in tumor progression. Here, we report that cancer cell motility requires inc...

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Autores principales: Shiraishi, Takumi, Verdone, James E., Huang, Jessie, Kahlert, Ulf D., Hernandez, James R., Torga, Gonzalo, Zarif, Jelani C., Epstein, Tamir, Gatenby, Robert, McCartney, Annemarie, Elisseeff, Jennifer H., Mooney, Steven M., An, Steven S., Pienta, Kenneth J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4381583/
https://www.ncbi.nlm.nih.gov/pubmed/25426557
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author Shiraishi, Takumi
Verdone, James E.
Huang, Jessie
Kahlert, Ulf D.
Hernandez, James R.
Torga, Gonzalo
Zarif, Jelani C.
Epstein, Tamir
Gatenby, Robert
McCartney, Annemarie
Elisseeff, Jennifer H.
Mooney, Steven M.
An, Steven S.
Pienta, Kenneth J.
author_facet Shiraishi, Takumi
Verdone, James E.
Huang, Jessie
Kahlert, Ulf D.
Hernandez, James R.
Torga, Gonzalo
Zarif, Jelani C.
Epstein, Tamir
Gatenby, Robert
McCartney, Annemarie
Elisseeff, Jennifer H.
Mooney, Steven M.
An, Steven S.
Pienta, Kenneth J.
author_sort Shiraishi, Takumi
collection PubMed
description The ability of a cancer cell to detach from the primary tumor and move to distant sites is fundamental to a lethal cancer phenotype. Metabolic transformations are associated with highly motile aggressive cellular phenotypes in tumor progression. Here, we report that cancer cell motility requires increased utilization of the glycolytic pathway. Mesenchymal cancer cells exhibited higher aerobic glycolysis compared to epithelial cancer cells while no significant change was observed in mitochondrial ATP production rate. Higher glycolysis was associated with increased rates of cytoskeletal remodeling, greater cell traction forces and faster cell migration, all of which were blocked by inhibition of glycolysis, but not by inhibition of mitochondrial ATP synthesis. Thus, our results demonstrate that cancer cell motility and cytoskeleton rearrangement is energetically dependent on aerobic glycolysis and not oxidative phosphorylation. Mitochondrial derived ATP is insufficient to compensate for inhibition of the glycolytic pathway with regard to cellular motility and CSK rearrangement, implying that localization of ATP derived from glycolytic enzymes near sites of active CSK rearrangement is more important for cell motility than total cellular ATP production rate. These results extend our understanding of cancer cell metabolism, potentially providing a target metabolic pathway associated with aggressive disease.
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spelling pubmed-43815832015-04-09 Glycolysis is the primary bioenergetic pathway for cell motility and cytoskeletal remodeling in human prostate and breast cancer cells Shiraishi, Takumi Verdone, James E. Huang, Jessie Kahlert, Ulf D. Hernandez, James R. Torga, Gonzalo Zarif, Jelani C. Epstein, Tamir Gatenby, Robert McCartney, Annemarie Elisseeff, Jennifer H. Mooney, Steven M. An, Steven S. Pienta, Kenneth J. Oncotarget Research Paper The ability of a cancer cell to detach from the primary tumor and move to distant sites is fundamental to a lethal cancer phenotype. Metabolic transformations are associated with highly motile aggressive cellular phenotypes in tumor progression. Here, we report that cancer cell motility requires increased utilization of the glycolytic pathway. Mesenchymal cancer cells exhibited higher aerobic glycolysis compared to epithelial cancer cells while no significant change was observed in mitochondrial ATP production rate. Higher glycolysis was associated with increased rates of cytoskeletal remodeling, greater cell traction forces and faster cell migration, all of which were blocked by inhibition of glycolysis, but not by inhibition of mitochondrial ATP synthesis. Thus, our results demonstrate that cancer cell motility and cytoskeleton rearrangement is energetically dependent on aerobic glycolysis and not oxidative phosphorylation. Mitochondrial derived ATP is insufficient to compensate for inhibition of the glycolytic pathway with regard to cellular motility and CSK rearrangement, implying that localization of ATP derived from glycolytic enzymes near sites of active CSK rearrangement is more important for cell motility than total cellular ATP production rate. These results extend our understanding of cancer cell metabolism, potentially providing a target metabolic pathway associated with aggressive disease. Impact Journals LLC 2014-11-16 /pmc/articles/PMC4381583/ /pubmed/25426557 Text en Copyright: © 2015 Shiraishi et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Shiraishi, Takumi
Verdone, James E.
Huang, Jessie
Kahlert, Ulf D.
Hernandez, James R.
Torga, Gonzalo
Zarif, Jelani C.
Epstein, Tamir
Gatenby, Robert
McCartney, Annemarie
Elisseeff, Jennifer H.
Mooney, Steven M.
An, Steven S.
Pienta, Kenneth J.
Glycolysis is the primary bioenergetic pathway for cell motility and cytoskeletal remodeling in human prostate and breast cancer cells
title Glycolysis is the primary bioenergetic pathway for cell motility and cytoskeletal remodeling in human prostate and breast cancer cells
title_full Glycolysis is the primary bioenergetic pathway for cell motility and cytoskeletal remodeling in human prostate and breast cancer cells
title_fullStr Glycolysis is the primary bioenergetic pathway for cell motility and cytoskeletal remodeling in human prostate and breast cancer cells
title_full_unstemmed Glycolysis is the primary bioenergetic pathway for cell motility and cytoskeletal remodeling in human prostate and breast cancer cells
title_short Glycolysis is the primary bioenergetic pathway for cell motility and cytoskeletal remodeling in human prostate and breast cancer cells
title_sort glycolysis is the primary bioenergetic pathway for cell motility and cytoskeletal remodeling in human prostate and breast cancer cells
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4381583/
https://www.ncbi.nlm.nih.gov/pubmed/25426557
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