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PKM2 and other key regulators of Warburg effect positively correlate with CD147 (EMMPRIN) gene expression and predict survival in multiple myeloma

Leukemia volume 31, pages 991–994 (2017)Cite this article

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Metabolic reprogramming is a hallmark of cancer and in contrast to normal differentiated cells that use oxidative phosphorylation in mitochondria to generate energy, cancer cells preferentially use the glycolytic pathway even when adequate oxygen is present. This phenomenon is called ‘aerobic glycolysis’ or the ‘Warburg effect’.1 It is regulated by several oncogenes2 and leads to upregulation of a series of metabolic enzymes along the glycolytic pathway.3 This altered metabolism results in high rates of glucose consumption and consequent lactate production.1 To maintain this metabolic phenotype, cancer cells upregulate a series of plasma membrane proteins, including proton-linked mono-carboxylate transporters (MCTs) that are needed to export lactate to prevent cell death owing to cellular acidosis because of lactate accumulation.4

Recent studies have shown that Warburg effect is operative in multiple myeloma (MM)5 with upregulation of key enzymes like the LDHA, GLUT1 and PDK1, as MM progresses from MGUS to MM.6 CD147, a multifunctional molecule contributes to this cellular metabolism by chaperoning MCTs to the plasma membrane and regulating their functional expression.7 The interaction of CD147 with MCT1 in particular results in export of lactate, thus maintaining the glycolytic flux in MM.7

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Acknowledgements

RF is a clinical investigator of the Damon Runyon Cancer Research Fund. This work is supported by grants R01 CA83724, ECOG CA 21115T, Predolin Foundation, Mayo Clinic Cancer Center and the Mayo Foundation.

Author contributions

SP and RF contributed to the conception and design of the study. SP performed research and analyzed the data. IS and SS contributed to data interpretation. SP drafted the article, and all authors read, revised the article critically for important intellectual content and gave final approval of the version to be published.

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  1. Division of Hematology-Oncology, Mayo Clinic, Scottsdale, AZ, USA

    S Panchabhai, I Schlam, S Sebastian & R Fonseca

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  1. S Panchabhai
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Correspondence to R Fonseca.

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Competing interests

RF has sponsored research from AMGEN, Celgene, Onyx and Sanofi. He has received consulting fees from Bayer, Novartis, Onyx, Pharmacyclics, Sanofi and serves on the advisory committee of Applied Biosciences. He has received a patent for the prognostication of MM based on genetic categorization of the disease. The remaining authors declare no conflict of interest.

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Panchabhai, S., Schlam, I., Sebastian, S. et al. PKM2 and other key regulators of Warburg effect positively correlate with CD147 (EMMPRIN) gene expression and predict survival in multiple myeloma. Leukemia 31, 991–994 (2017). https://doi.org/10.1038/leu.2016.389

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