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

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)130-143
Number of pages14
JournalOncotarget
Volume6
Issue number1
DOIs
StatePublished - Jan 1 2015

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Keywords

  • Cancer Metabolism
  • Cytoskeleton
  • Glycolysis
  • Metastasis
  • Motility

ASJC Scopus subject areas

  • Oncology

Cite this

Shiraishi, T., Verdone, J. E., Huang, J., Kahlert, U. D., Hernandez, J. R., Torga, G., Zarif, J. C., Epstein, T., Gatenby, R., McCartney, A., Elisseeff, J. H., Mooney, S. M., An, S. S., & Pienta, K. J. (2015). Glycolysis is the primary bioenergetic pathway for cell motility and cytoskeletal remodeling in human prostate and breast cancer cells. Oncotarget, 6(1), 130-143. https://doi.org/10.18632/oncotarget.2766