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

Takumi Shiraishi; James E Verdone; Jessie Huang; Ulf D Kahlert; James R Hernandez; Gonzalo Torga; Jelani C Zarif; Tamir Epstein; Robert Gatenby; Annemarie McCartney; Jennifer H Elisseeff; Steven M Mooney; Steven S An; Kenneth J Pienta

doi:10.18632/oncotarget.2766

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

Journal article

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

Takumi Shiraishi, James E Verdone, Jessie Huang, Ulf D Kahlert, James R Hernandez, Gonzalo Torga, Jelani C Zarif, Tamir Epstein, Robert Gatenby, Annemarie McCartney, …

Oncotarget, Vol.6(1), pp.130-143

01/01/2015

DOI: https://doi.org/10.18632/oncotarget.2766

PMCID: PMC4381583

PMID: 25426557

Abstract

Prostatic Neoplasms - metabolism

Neoplastic Stem Cells - cytology

Aerobiosis

DNA, Mitochondrial - metabolism

Microscopy, Phase-Contrast

Humans

Gene Expression Regulation, Neoplastic

Oxidative Phosphorylation

Male

Mitochondria - metabolism

Breast Neoplasms - metabolism

Mesenchymal Stromal Cells - cytology

Phenotype

Oxygen - chemistry

Cytoskeleton - metabolism

Glycolysis

Female

Adenosine Triphosphate - chemistry

Epithelial Cells - cytology

Cell Movement

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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Title: Glycolysis is the primary bioenergetic pathway for cell motility and cytoskeletal remodeling in human prostate and breast cancer cells
Creators: Takumi Shiraishi - Department of Urology, The James Buchanan Brady Urological Institute, Johns Hopkins University, Baltimore, MD, USA
James E Verdone - Department of Urology, The James Buchanan Brady Urological Institute, Johns Hopkins University, Baltimore, MD, USA
Jessie Huang - Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
Ulf D Kahlert - Department of Pathology, Division of Neuropathology, The Johns Hopkins Hospital, Baltimore, MD, USA
James R Hernandez - Department of Urology, The James Buchanan Brady Urological Institute, Johns Hopkins University, Baltimore, MD, USA
Gonzalo Torga - Department of Urology, The James Buchanan Brady Urological Institute, Johns Hopkins University, Baltimore, MD, USA
Jelani C Zarif - Department of Urology, The James Buchanan Brady Urological Institute, Johns Hopkins University, Baltimore, MD, USA
Tamir Epstein - Department of Integrative Mathematical Oncology and Department of Diagnostic Imaging, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA
Robert Gatenby - Department of Integrative Mathematical Oncology and Department of Diagnostic Imaging, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA
Annemarie McCartney - The Wilmer Eye Institute and Department of Biomedical Engineering, Baltimore, MD, USA
Jennifer H Elisseeff - The Wilmer Eye Institute and Department of Biomedical Engineering, Baltimore, MD, USA
Steven M Mooney - Department of Urology, The James Buchanan Brady Urological Institute, Johns Hopkins University, Baltimore, MD, USA
Steven S An - Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, USA. Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. In Vivo Cellular and Molecular Imaging Center, The Johns Hopkins School of Medicine, Baltimore, MD, USA
Kenneth J Pienta - Department of Urology, The James Buchanan Brady Urological Institute, Johns Hopkins University, Baltimore, MD, USA. Department of Oncology, Johns Hopkins University, Baltimore, MD, USA. Department of Pharmacology and Molecular Sciences, Johns Hopkins University, Baltimore, MD, USA. Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, USA
Publication Details: Oncotarget, Vol.6(1), pp.130-143
Date published: 01/01/2015
Grant note: P01 CA093900 / NCI NIH HHS 1P01CA093900 / NCI NIH HHS P50CA103175 / NCI NIH HHS U01CA143055 / NCI NIH HHS U54CA141868 / NCI NIH HHS R25 CA174664 / NCI NIH HHS R01 HL107361 / NHLBI NIH HHS HL107361 / NHLBI NIH HHS R01 CA163214 / NCI NIH HHS U01 CA143055 / NCI NIH HHS R43 CA141868 / NCI NIH HHS P50 CA103175 / NCI NIH HHS T32 GM008752 / NIGMS NIH HHS U54CA163214 / NCI NIH HHS T32 GM007309 / NIGMS NIH HHS U54 CA143868 / NCI NIH HHS
Academic Unit: Clinical and Translational Research
Language: English
Resource Type: Journal article
Identifiers: 991031654477104646