A role for the mitochondrial pyruvate carrier as a repressor of the warburg effect and colon cancer cell growth

John C. Schell, Kristofor A. Olson, Lei Jiang, Amy J. Hawkins, Jonathan G. VanVranken, Jianxin Xie, Robert A. Egnatchik, Espen G. Earl, Ralph J. DeBerardinis, Jared Rutter

Research output: Contribution to journalArticle

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Abstract

Cancer cells are typically subject to profound metabolic alterations, including the Warburg effect wherein cancer cells oxidize a decreased fraction of the pyruvate generated from glycolysis. We show herein that the mitochondrial pyruvate carrier (MPC), composed of the products of the MPC1 and MPC2 genes, modulates fractional pyruvate oxidation. MPC1 is deleted or underexpressed in multiple cancers and correlates with poor prognosis. Cancer cells re-expressing MPC1 and MPC2 display increased mitochondrial pyruvate oxidation, with no changes in cell growth in adherent culture. MPC re-expression exerted profound effects in anchorage-independent growth conditions, however, including impaired colony formation in soft agar, spheroid formation, and xenograft growth. We also observed a decrease in markers of stemness and traced the growth effects of MPC expression to the stem cell compartment. We propose that reduced MPC activity is an important aspect of cancer metabolism, perhaps through altering the maintenance and fate of stem cells.

Original languageEnglish (US)
Pages (from-to)400-413
Number of pages14
JournalMolecular Cell
Volume56
Issue number3
DOIs
StatePublished - 2014

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Colonic Neoplasms
Pyruvic Acid
Growth
Neoplasms
Stem Cells
Glycolysis
Heterografts
Agar
Maintenance
pyruvate transport protein
Genes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Schell, J. C., Olson, K. A., Jiang, L., Hawkins, A. J., VanVranken, J. G., Xie, J., ... Rutter, J. (2014). A role for the mitochondrial pyruvate carrier as a repressor of the warburg effect and colon cancer cell growth. Molecular Cell, 56(3), 400-413. https://doi.org/10.1016/j.molcel.2014.09.026

A role for the mitochondrial pyruvate carrier as a repressor of the warburg effect and colon cancer cell growth. / Schell, John C.; Olson, Kristofor A.; Jiang, Lei; Hawkins, Amy J.; VanVranken, Jonathan G.; Xie, Jianxin; Egnatchik, Robert A.; Earl, Espen G.; DeBerardinis, Ralph J.; Rutter, Jared.

In: Molecular Cell, Vol. 56, No. 3, 2014, p. 400-413.

Research output: Contribution to journalArticle

Schell, JC, Olson, KA, Jiang, L, Hawkins, AJ, VanVranken, JG, Xie, J, Egnatchik, RA, Earl, EG, DeBerardinis, RJ & Rutter, J 2014, 'A role for the mitochondrial pyruvate carrier as a repressor of the warburg effect and colon cancer cell growth', Molecular Cell, vol. 56, no. 3, pp. 400-413. https://doi.org/10.1016/j.molcel.2014.09.026
Schell, John C. ; Olson, Kristofor A. ; Jiang, Lei ; Hawkins, Amy J. ; VanVranken, Jonathan G. ; Xie, Jianxin ; Egnatchik, Robert A. ; Earl, Espen G. ; DeBerardinis, Ralph J. ; Rutter, Jared. / A role for the mitochondrial pyruvate carrier as a repressor of the warburg effect and colon cancer cell growth. In: Molecular Cell. 2014 ; Vol. 56, No. 3. pp. 400-413.
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