Abstract
Background:
The Warburg effect is one of the hallmarks of cancer and rapidly proliferating cells. It is known that the hypoxia-inducible factor 1-alpha (HIF1A) and MYC proteins cooperatively regulate expression of the HK2 and PDK1 genes, respectively, in the Burkitt lymphoma (BL) cell line P493-6, carrying an inducible MYC gene repression system. However, the mechanism of aerobic glycolysis in BL cells has not yet been fully understood.
Methods and findings:
Western blot analysis showed that the HIF1A protein was highly expressed in Epstein-Barr virus (EBV)-positive BL cell lines. Using biochemical assays and quantitative PCR (Q-PCR), we found that-unlike in lymphoblastoid cell lines (LCLs)-the MYC protein was the master regulator of the Warburg effect in these BL cell lines. Inhibition of the transactivation ability of MYC had no influence on aerobic glycolysis in LCLs, but it led to decreased expression of MYC-dependent genes and lactate dehydrogenase A (LDHA) activity in BL cells.
Conclusions:
Our data suggest that aerobic glycolysis, or the Warburg effect, in BL cells is regulated by MYC expressed at high levels, whereas in LCLs, HIF1A is responsible for this phenomenon.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Burkitt Lymphoma / genetics
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Burkitt Lymphoma / metabolism*
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Burkitt Lymphoma / pathology
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Cell Line, Tumor
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Glycolysis*
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Humans
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Hypoxia-Inducible Factor 1, alpha Subunit / biosynthesis
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Hypoxia-Inducible Factor 1, alpha Subunit / genetics
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Kinesins / biosynthesis
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Kinesins / genetics
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Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics
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Precursor Cell Lymphoblastic Leukemia-Lymphoma / metabolism*
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Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology
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Protein Serine-Threonine Kinases / biosynthesis
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Protein Serine-Threonine Kinases / genetics
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Proto-Oncogene Proteins c-myc / biosynthesis
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Proto-Oncogene Proteins c-myc / genetics
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Pyruvate Dehydrogenase Acetyl-Transferring Kinase
Substances
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HIF1A protein, human
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Hypoxia-Inducible Factor 1, alpha Subunit
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KIF2A protein, human
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MYC protein, human
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PDK1 protein, human
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Proto-Oncogene Proteins c-myc
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Pyruvate Dehydrogenase Acetyl-Transferring Kinase
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Protein Serine-Threonine Kinases
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Kinesins
Grants and funding
This work was supported by the Swedish Cancer Society, by matching grants from the Concern Foundation (Los Angeles) and the Cancer Research Institute (New York), by the Swedish Institute and by Karolinska Institutet. The funders had no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript.