The DOI matches its Crossref record; 47 of the 47 references it cites were found in a registry or an index; none of the 68 sources its claims cite is checked for support yet.
Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation
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Fuel Economy for Growing Cells: Sophisticated 21st-century analyses of the signaling pathways that control cell growth have led researchers back to the seminal work of Otto Warburg, who discovered in the 1920s that tumor cells generate their energy in an unusual way—by switching from mitochondrial respiration to glycolysis. The advantage conferred by this metabolic switch is puzzling because mitochondrial respiration is a more efficient way to produce ATP. Vander Heiden et al. (p. 1029 ) review arguments that rapidly growing cells have critical metabolic requirements that extend beyond ATP and that a better understanding of these requirements may shed new light on the “Warburg effect” and ultimately lead to new therapies for cancer.
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“This 35-fold asymmetry is only partially compensated by the consumption of 3 glucose molecules in acetyl-CoA production to satisfy the carbon requirement of the acyl chain itself.”
§ Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation > Crunching the Numbers–What Are the Metabolic Needs of Proliferating Cells?
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“Some glucose must be diverted to macromolecular precursors such as acetyl-CoA for fatty acids, glycolytic intermediates for nonessential amino acids, and ribose for nucleotides.”
§ Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation > Crunching the Numbers–What Are the Metabolic Needs of Proliferating Cells?
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“Inhibiting LDH activity impairs cell proliferation (6)”
§ Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation > Crunching the Numbers–What Are the Metabolic Needs of Proliferating Cells?
What the sources say
- Not checked yetcites [6] Fantin VR St-Pierre J Leder P Cancer Cell 9 425 2006 16766262
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In the paper
“Most of the carbon for fatty acid synthesis is derived from glucose.”
§ Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation > Crunching the Numbers–What Are the Metabolic Needs of Proliferating Cells?
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In the paper
“Normal proliferating cells can also undergo cell cycle arrest and reactivate catabolic metabolism when their ability to produce ATP from glucose is compromised (12, 13)”
§ Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation > Why Do Proliferating Cells Switch to a Less Efficient Metabolism?
What the sources say
- Not checked yetcites [12] Shaw RJ Proc Natl Acad Sci USA 101 3329 2004 14985505 PMC373461
- Not checked yetcites [13] Lum JJ Cell 120 237 2005 15680329
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In the paper
“subsequent work showed that mitochondrial function is not impaired in most cancer cells (5–7)”
§ Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation > Proliferating Mammalian Cells Exhibit Anabolic Metabolism
What the sources say
- Not checked yetcites [5] Weinhouse S Z Krebsforsch Klin Onkol Cancer Res Clin Oncol 87 115 1976 136820
- Not checked yetcites [6] Fantin VR St-Pierre J Leder P Cancer Cell 9 425 2006 16766262
- Not checked yetcites [7] Moreno-Sanchez R Rodriguez-Enriquez S Marin-Hernandez A Saavedra E FEBS J 274 1393 2007 17302740
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“This may explain at least part of the selective advantage provided by the Warburg effect”
§ Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation > Crunching the Numbers–What Are the Metabolic Needs of Proliferating Cells?
What the sources say
- Not checked yetcites [16] DeBerardinis RJ Proc Natl Acad Sci USA 104 19345 2007 18032601 PMC2148292
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In the paper
“To produce two viable daughter cells at mitosis, a proliferating cell must replicate all of its cellular contents. This imposes a large requirement for nucleotides, amino acids, and lipids.”
§ Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation > Crunching the Numbers–What Are the Metabolic Needs of Proliferating Cells?
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In the paper
“even minor perturbations in the ATP/ADP ratio can impair growth”
§ Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation > Why Do Proliferating Cells Switch to a Less Efficient Metabolism?
What the sources say
- Not checked yetcites [10] Izyumov DS Biochim Biophys Acta 1658 141 2004 15282185
- Not checked yetcites [11] Vander Heiden MG Chandel NS Schumacker PT Thompson CB Mol Cell 3 159 1999 10078199
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In the paper
“glucose and glutamine supply most of the carbon, nitrogen, free energy, and reducing equivalents necessary to support cell growth and division”
§ Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation > Crunching the Numbers–What Are the Metabolic Needs of Proliferating Cells?
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- Rests on an assumption: For most mammalian cells in culture, glucose and glutamine are the only two molecules catabolized in appreciable quantities.
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In the paper
“most cancer cells instead rely on aerobic glycolysis, a phenomenon termed “the Warburg effect.””
- Also stated in: § Proliferating Mammalian Cells Exhibit Anabolic Metabolism · plain
“most cancer cells produce large amounts of lactate regardless of the availability of oxygen and hence their metabolism is often referred to as “aerobic glycolysis.””
§ Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation > Abstract
What the sources say
- Not checked yetcites [3] Warburg O Posener K Negelein E Biochem Z 152 319 1924
- Not checked yetcites [4] Warburg O Science 123 309 1956 13298683
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- Also stated in: § Proliferating Mammalian Cells Exhibit Anabolic Metabolism · plain
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In the paper
“there is evidence that ATP may never be limiting in these cells”
§ Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation > Why Do Proliferating Cells Switch to a Less Efficient Metabolism?
What the sources say
- Not checked yetcites [2] Deberardinis RJ Lum JJ Hatzivassiliou G Thompson CB Cell Metab 7 11 2008 18177721
- Not checked yetcites [9] Christofk HR Nature 452 230 2008 18337823
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In the paper
“converting all of the glucose to CO2 via oxidative phosphorylation in the mitochondria to maximize ATP production runs counter to the needs of a proliferating cell”
§ Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation > Crunching the Numbers–What Are the Metabolic Needs of Proliferating Cells?
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In the paper
“the catabolism of glutamine into lactate produces NADPH via the activity of NADP+-specific malate dehydrogenase (malic enzyme)”
§ Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation > Crunching the Numbers–What Are the Metabolic Needs of Proliferating Cells?
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In the paper
“Under conditions of high ATP/ADP and NADH/NAD+ exhibited by most proliferating cells, this citrate is excreted back into the cytosol where lipids are generated.”
§ Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation > Crunching the Numbers–What Are the Metabolic Needs of Proliferating Cells?
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In the paper
“Elimination of excess carbon might be required to generate sufficient NADPH to support cell proliferation.”
§ Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation > Crunching the Numbers–What Are the Metabolic Needs of Proliferating Cells?
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In the paper
“if this were the case, the resulting rise in the ATP/ADP ratio would severely impair the flux through glycolytic intermediates, limiting the production of the acetyl-CoA and NADPH required for macromolecular synthesis”
§ Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation > Crunching the Numbers–What Are the Metabolic Needs of Proliferating Cells?
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In the paper
“This demonstrates that aerobic glycolytic metabolism can provide sufficient energy for cell proliferation.”
§ Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation > Why Do Proliferating Cells Switch to a Less Efficient Metabolism?
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In the paper
“cells using aerobic glycolysis also exhibit high ratios of ATP/ADP (adenosine 5′-diphosphate) and NADH/NAD+ (2, 9)”
§ Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation > Why Do Proliferating Cells Switch to a Less Efficient Metabolism?
What the sources say
- Not checked yetcites [2] Deberardinis RJ Lum JJ Hatzivassiliou G Thompson CB Cell Metab 7 11 2008 18177721
- Not checked yetcites [9] Christofk HR Nature 452 230 2008 18337823
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In the paper
“It is clear that for a cell to proliferate, the bulk of the glucose cannot be committed to carbon catabolism for ATP production.”
§ Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation > Crunching the Numbers–What Are the Metabolic Needs of Proliferating Cells?
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In the paper
“glioblastoma cells in culture convert as much as 90% of glucose and 60% of glutamine they acquire into lactate or alanine (16)”
§ Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation > Crunching the Numbers–What Are the Metabolic Needs of Proliferating Cells?
What the sources say
- Not checked yetcites [16] DeBerardinis RJ Proc Natl Acad Sci USA 104 19345 2007 18032601 PMC2148292
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In the paper
“synthesis of amino acids and nucleotides also consumes more equivalents of carbon and NADPH than of ATP”
§ Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation > Crunching the Numbers–What Are the Metabolic Needs of Proliferating Cells?
What the sources say
- Not checked yetcites [8] Lehninger AL Nelson DL Cox MM Principles of Biochemistry Worth New York 2 1993
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In the paper
“it is the low-activity form of PK-M2 that is necessary for cell proliferation”
§ Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation > Metabolic Regulation Is a Component of the Cell Growth Machinery
What the sources say
- Not checked yetcites [9] Christofk HR Nature 452 230 2008 18337823
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In the paper
“Monoallelic mutation of the same residue in IDH1, or the analogous residue in the related enzyme IDH2, is a common feature of gliomas as more than 80% of indolent gliomas harbor such a mutation (28, 29).”
§ Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation > Metabolic Regulation Is a Component of the Cell Growth Machinery
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“In response to phosphotyrosine-protein binding, PK-M2 is induced into a low-activity state.”
§ Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation > Metabolic Regulation Is a Component of the Cell Growth Machinery
What the sources say
- Not checked yetcites [17] Christofk HR Vander Heiden MG Wu N Asara JM Cantley LC Nature 452 181 2008 18337815
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In the paper
“genes involved in glutamine metabolism appear to be under both the direct and indirect transcriptional control of the MYC protein (32, 33)”
§ Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation > Metabolic Regulation Is a Component of the Cell Growth Machinery
What the sources say
hedgeddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“up to 12% of the tumors harbor the same point mutation in the gene encoding cytosolic isocitrate dehydrogenase–1 (IDH1) (27)”
§ Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation > Metabolic Regulation Is a Component of the Cell Growth Machinery
What the sources say
- Not checked yetcites [27] Parsons DW Science 321 1807 2008 18772396 PMC2820389
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In the paper
“there is emerging evidence that cellular metabolism within a tumor can be heterogeneous, with some cells using the excess lactate generated as a fuel for mitochondrial oxidative phosphorylation (19)”
§ Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation > Crunching the Numbers–What Are the Metabolic Needs of Proliferating Cells?
What the sources say
- Not checked yetcites [19] Sonveaux P J Clin Invest 118 3930 2008 19033663 PMC2582933
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In the paper
“proliferating cells selectively express the M2 isoform of the glycolytic enzyme pyruvate kinase (PK-M2) (9)”
§ Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation > Metabolic Regulation Is a Component of the Cell Growth Machinery
What the sources say
- Not checked yetcites [9] Christofk HR Nature 452 230 2008 18337823
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“For most proliferating cells, nutrients are not limiting so there is no selective pressure to optimize metabolism for ATP yield.”
§ Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation > Crunching the Numbers–What Are the Metabolic Needs of Proliferating Cells?
plain- Asserted: passes — The authors put it forward as true.
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- Rests on an assumption: Nutrients are not limiting for most proliferating cells.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“metabolism of both glutamine and glucose is orchestrated to support the production of acetyl-CoA and NADPH needed for fatty acid synthesis”
§ Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation > Crunching the Numbers–What Are the Metabolic Needs of Proliferating Cells?
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In the paper
“where it has been examined in cancer patients, response to therapy is predicted by the ability to disrupt glucose metabolism as measured by FDG-PET (23)”
§ Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation > Metabolic Regulation Is a Component of the Cell Growth Machinery
What the sources say
- Not checked yetcites [23] Ben-Haim S Ell P J Nucl Med 50 88 2009 19139187
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In the paper
“Unlike other pyruvate kinase isoforms, PK-M2 is regulated by tyrosine-phosphorylated proteins (17).”
§ Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation > Metabolic Regulation Is a Component of the Cell Growth Machinery
What the sources say
- Not checked yetcites [17] Christofk HR Vander Heiden MG Wu N Asara JM Cantley LC Nature 452 181 2008 18337815
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“this dependence on glutamine for survival is not related to the generation of ATP by glutamine metabolism”
§ Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation > Metabolic Regulation Is a Component of the Cell Growth Machinery
What the sources say
- Not checked yetcites [31] Yuneva M Zamboni N Oefner P Sachidanandam R Lazebnik Y J Cell Biol 178 93 2007 17606868 PMC2064426
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“PI3K pathway activation renders cells dependent on high levels of glucose flux (20)”
§ Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation > Metabolic Regulation Is a Component of the Cell Growth Machinery
What the sources say
- Not checked yetcites [20] Buzzai M Oncogene 24 4165 2005 15806154
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“This maladaptive metabolic state may underlie the evolutionary selection for induction of apoptosis and/or senescence in the setting of increased ROS.”
§ Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation > Metabolic Regulation Is a Component of the Cell Growth Machinery
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In the paper
“Germline mutations in the TCA cycle enzymes succinate dehydrogenase and fumarate hydratase have been identified in some forms of human renal cell cancer, paraganglioma, and pheochromocytoma (24, 25).”
§ Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation > Metabolic Regulation Is a Component of the Cell Growth Machinery
What the sources say
- Not checked yetcites [24] Baysal BE Science 287 848 2000 10657297
- Not checked yetcites [25] Pollard PJ Wortham NC Tomlinson IP Ann Med 35 634 2003 14708972
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In the paper
“Human tumor cells whose growth is driven by the MYC oncogene are particularly sensitive to glutamine withdrawal (31)”
§ Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation > Metabolic Regulation Is a Component of the Cell Growth Machinery
What the sources say
- Not checked yetcites [31] Yuneva M Zamboni N Oefner P Sachidanandam R Lazebnik Y J Cell Biol 178 93 2007 17606868 PMC2064426
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In the paper
“One effect of these mutations is activation of Hif1α-mediated glucose utilization (26).”
§ Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation > Metabolic Regulation Is a Component of the Cell Growth Machinery
What the sources say
- Not checked yetcites [26] Selak MA Cancer Cell 7 77 2005 15652751
plaindirect- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In contrast, a selective pressure for rate of metabolism does exist.”
§ Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation > Crunching the Numbers–What Are the Metabolic Needs of Proliferating Cells?
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In the paper
“Phosphotyrosine signaling downstream of a variety of cell growth signals shares the common ability to negatively regulate PK-M2 activity (17).”
§ Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation > Metabolic Regulation Is a Component of the Cell Growth Machinery
What the sources say
- Not checked yetcites [17] Christofk HR Vander Heiden MG Wu N Asara JM Cantley LC Nature 452 181 2008 18337815
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“PK-M2 is required for proliferation in vivo (9).”
§ Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation > Metabolic Regulation Is a Component of the Cell Growth Machinery
What the sources say
- Not checked yetcites [9] Christofk HR Nature 452 230 2008 18337823
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Glutamine uptake also appears to be critical for lipid synthesis in that it supplies carbon in the form of mitochondrial oxaloacetate to maintain citrate production in the first step of the TCA cycle (16).”
§ Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation > Crunching the Numbers–What Are the Metabolic Needs of Proliferating Cells?
What the sources say
- Not checked yetcites [16] DeBerardinis RJ Proc Natl Acad Sci USA 104 19345 2007 18032601 PMC2148292
hedgeddirect- Asserted: passes — The authors put it forward as true.
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- Based: passes — The paper gives a reason why it holds.
In the paper
“Glutamine depletion from MYC-transformed cells results in the rapid loss of TCA cycle intermediates and cell death (31).”
§ Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation > Metabolic Regulation Is a Component of the Cell Growth Machinery
What the sources say
- Not checked yetcites [31] Yuneva M Zamboni N Oefner P Sachidanandam R Lazebnik Y J Cell Biol 178 93 2007 17606868 PMC2064426
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Cells that convert glucose and glutamine into biomass most efficiently will proliferate fastest.”
§ Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation > Crunching the Numbers–What Are the Metabolic Needs of Proliferating Cells?
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
In the paper
“the PI3K pathway regulates glucose uptake and utilization (Fig. 3)”
§ Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation > Metabolic Regulation Is a Component of the Cell Growth Machinery
What the sources say
- Not checked yetcites [2] Deberardinis RJ Lum JJ Hatzivassiliou G Thompson CB Cell Metab 7 11 2008 18177721
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Cells with excess nutrient uptake that have not converted to aerobic glycolysis would be predicted to have increased oxidative phosphorylation and ROS production.”
§ Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation > Metabolic Regulation Is a Component of the Cell Growth Machinery
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“stationary-phase yeast lose viability when exposed to high levels of glucose and no additional nutrients (37)”
§ Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation > Metabolic Regulation Is a Component of the Cell Growth Machinery
What the sources say
- Not checked yetcites [37] Granot D Snyder M Proc Natl Acad Sci USA 88 5724 1991 1648229 PMC51950
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“lung tumors arising in the airways exhibit aerobic glycolysis even though these tumor cells are exposed to oxygen during tumorigenesis (9, 42)”
§ Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation > What Triggers the Switch from Oxidative Phosphorylation to Aerobic Glycolysis?
What the sources say
- Not checked yetcites [9] Christofk HR Nature 452 230 2008 18337823
- Not checked yetcites [42] Nolop KB Cancer 60 2682 1987 3499969
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“cancer cells appear to use glycolytic metabolism before exposure to hypoxic conditions”
§ Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation > What Triggers the Switch from Oxidative Phosphorylation to Aerobic Glycolysis?
What the sources say
- Not checked yetcites [40] Gottschalk S Anderson N Hainz C Eckhardt SG Serkova NJ Clin Cancer Res 10 6661 2004 15475456
- Not checked yetcites [41] Elstrom RL Cancer Res 64 3892 2004 15172999
- Not checked yetcites [9] Christofk HR Nature 452 230 2008 18337823
- Not checked yetcites [42] Nolop KB Cancer 60 2682 1987 3499969
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“For normal proliferating tissues, such as in the developing embryo or during an immune response in the adult, signals from growth factors allow cells to utilize nutrients for growth (41, 43).”
§ Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation > What Triggers the Switch from Oxidative Phosphorylation to Aerobic Glycolysis?
What the sources say
- Not checked yetcites [41] Elstrom RL Cancer Res 64 3892 2004 15172999
- Not checked yetcites [43] Kondoh H Antioxid Redox Signal 9 293 2007 17184172
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“the evolving evidence instead points to a dynamically regulated system that is programmed to fit the requirements for cell proliferation or meet the specific needs of each differentiated tissue as appropriate”
§ Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation > What Triggers the Switch from Oxidative Phosphorylation to Aerobic Glycolysis?
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Alterations in the appropriate balance of fuels and/or signal transduction pathways that deal with nutrient utilization may underlie the cancer predisposition associated with metabolic diseases such as diabetes and obesity (45, 46).”
§ Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation > Cellular Metabolism and Human Cancer
What the sources say
- Not checked yetcites [45] Calle EE Kaaks R Nat Rev Cancer 4 579 2004 15286738
- Not checked yetcites [46] Pollak M Nat Rev Cancer 8 915 2008 19029956
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“for cancer to arise, mutations are needed to give cells the ability to acquire nutrients and coordinately regulate metabolic pathways to support proliferation”
§ Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation > What Triggers the Switch from Oxidative Phosphorylation to Aerobic Glycolysis?
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“The growing evidence that activation of PI3K causes increased dependency on glycolysis”
§ Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation > Cellular Metabolism and Human Cancer
What the sources say
- Not checked yetcites [20] Buzzai M Oncogene 24 4165 2005 15806154
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- It may state two separate claims as one. 19
- Probably not a substantial claim. 6
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“to make a 16-carbon fatty acyl chain, a single glucose molecule can provide five times the ATP required, whereas 7 glucose molecules are needed to generate the NADPH required”
§ Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation > Crunching the Numbers–What Are the Metabolic Needs of Proliferating Cells?
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“synthesis of palmitate, a major constituent of cellular membranes, requires 7 molecules of ATP, 16 carbons from 8 molecules of acetyl-CoA (coenzyme A), and 28 electrons from 14 molecules of NADPH”
§ Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation > Crunching the Numbers–What Are the Metabolic Needs of Proliferating Cells?
What the sources say
- Not checked yetcites [8] Lehninger AL Nelson DL Cox MM Principles of Biochemistry Worth New York 2 1993
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“Synthesis of acetyl-CoA from citrate requires the enzyme ATP citrate lyase (ACL), and disruption of ACL impairs tumor growth (18).”
§ Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation > Crunching the Numbers–What Are the Metabolic Needs of Proliferating Cells?
What the sources say
- Not checked yetcites [18] Hatzivassiliou G Cancer Cell 8 311 2005 16226706
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“A second possible explanation for the switch to aerobic glycolysis, discussed in detail below, is that proliferating cells have important metabolic requirements that extend beyond ATP.”
§ Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation > Why Do Proliferating Cells Switch to a Less Efficient Metabolism?
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Growth factor signaling also regulates the activity of the glycolytic enzyme pyruvate kinase and modulates flux of carbon through the later steps of glycolysis (9, 17).”
§ Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation > Crunching the Numbers–What Are the Metabolic Needs of Proliferating Cells?
What the sources say
- Not checked yetcites [9] Christofk HR Nature 452 230 2008 18337823
- Not checked yetcites [17] Christofk HR Vander Heiden MG Wu N Asara JM Cantley LC Nature 452 181 2008 18337815
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“A glucose molecule can generate up to 36 ATPs, or 30 ATPs and 2 NADPHs [if diverted into the pentose phosphate shunt (8, 15)], or provide 6 carbons for macromolecular synthesis.”
§ Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation > Crunching the Numbers–What Are the Metabolic Needs of Proliferating Cells?
What the sources say
- Not checked yetcites [8] Lehninger AL Nelson DL Cox MM Principles of Biochemistry Worth New York 2 1993
- Not checked yetcites [15] Possibly up to four NADPH molecules per glucose can be produced if the products of the pentose phosphate shunt are metabolized via the TCA cycle and malic enzyme or cytosolic isocitrate dehydrogenase 1 (IDH1) to generate two additional NADPH molecules.
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“The metabolism of glucose to lactate generates only 2 ATPs per molecule of glucose, whereas oxidative phosphorylation generates up to 36 ATPs upon complete oxidation of one glucose molecule (8).”
§ Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation > Why Do Proliferating Cells Switch to a Less Efficient Metabolism?
What the sources say
- Not checked yetcites [8] Lehninger AL Nelson DL Cox MM Principles of Biochemistry Worth New York 2 1993
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
In the paper
“Glucose withdrawal induces cell death in a manner indistinguishable from that seen upon withdrawal of growth factor signaling, a phenomenon that may contribute to “oncogene addiction” (22).”
§ Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation > Metabolic Regulation Is a Component of the Cell Growth Machinery
What the sources say
- Not checked yetcites [22] Vander Heiden MG Mol Cell Biol 21 5899 2001 11486029 PMC87309
hedgeddirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
In the paper
“PI3K signaling through AKT can regulate glucose transporter expression, enhance glucose capture by hexokinase, and stimulate phosphofructokinase activity (2)”
§ Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation > Metabolic Regulation Is a Component of the Cell Growth Machinery
What the sources say
- Not checked yetcites [2] Deberardinis RJ Lum JJ Hatzivassiliou G Thompson CB Cell Metab 7 11 2008 18177721
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Small molecules that disrupt PI3K signaling lead to decreased glucose uptake by tumors as measured by 18F-deoxyglucose positron emission tomography (FDG-PET), and the ability to inhibit tumor FDG uptake correlates with tumor regression (21).”
§ Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation > Metabolic Regulation Is a Component of the Cell Growth Machinery
What the sources say
- Not checked yetcites [21] Engelman JA Nat Med 14 1351 2008 19029981 PMC2683415
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“p53 expression controls metabolic genes and alters glucose utilization”
§ Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation > Metabolic Regulation Is a Component of the Cell Growth Machinery
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Expression of TIGAR, a gene induced by p53, leads to inhibition of phosphofructokinase, redirection of glucose toward the pentose phosphate shunt, and NADPH production (34).”
§ Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation > Metabolic Regulation Is a Component of the Cell Growth Machinery
What the sources say
- Not checked yetcites [34] Bensaad K Cell 126 107 2006 16839880
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Possibly the dumping of excess carbon as lactate is effective because it allows faster incorporation of carbon into biomass, which in turn facilitates rapid cell division.”
§ Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation > Crunching the Numbers–What Are the Metabolic Needs of Proliferating Cells?
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“oncogenic Ras causes alterations in glucose metabolism (35) but causes senescence when expressed in cells without a cooperating oncogene (36)”
§ Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation > Metabolic Regulation Is a Component of the Cell Growth Machinery
What the sources say
- Not checked yetcites [35] Chiaradonna F Oncogene 25 5391 2006 16607279
- Not checked yetcites [36] Serrano M Lin AW McCurrach ME Beach D Lowe SW Cell 88 593 1997 9054499
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
In the paper
“The Cori cycle in the liver can recycle lactate generated from actively proliferating tissues to glucose, and analogous pathways exist to recycle the alanine generated from “inefficient” glutamine metabolism (8).”
§ Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation > Crunching the Numbers–What Are the Metabolic Needs of Proliferating Cells?
What the sources say
- Not checked yetcites [8] Lehninger AL Nelson DL Cox MM Principles of Biochemistry Worth New York 2 1993
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“IDH1 and IDH2 couple the interconversion of cytosolic isocitrate and α-ketoglutarate in an NADP+/NADPH-dependent reaction.”
§ Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation > Metabolic Regulation Is a Component of the Cell Growth Machinery
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Mitochondrial oxidative phosphorylation is the major cellular source of ROS production.”
§ Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation > Metabolic Regulation Is a Component of the Cell Growth Machinery
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“leukemic cells are highly glycolytic (40, 41), yet these cells reside within the bloodstream at higher oxygen tensions than cells in most normal tissues”
§ Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation > What Triggers the Switch from Oxidative Phosphorylation to Aerobic Glycolysis?
What the sources say
- Not checked yetcites [40] Gottschalk S Anderson N Hainz C Eckhardt SG Serkova NJ Clin Cancer Res 10 6661 2004 15475456
- Not checked yetcites [41] Elstrom RL Cancer Res 64 3892 2004 15172999
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Perhaps one function of oncogenic pathways is to drive cell-autonomous nutrient uptake and program proliferative metabolism, whereas one function of tumor suppressor pathways is to prevent nutrient utilization for anabolic processes.”
§ Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation > What Triggers the Switch from Oxidative Phosphorylation to Aerobic Glycolysis?
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“the available evidence suggests that it is a late-occurring event that may not be a major contributor in the switch to aerobic glycolysis by cancer cells”
§ Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation > What Triggers the Switch from Oxidative Phosphorylation to Aerobic Glycolysis?
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“There is mounting evidence for cross-talk between signaling pathways and metabolic control in every multicellular organism studied.”
§ Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation > Future Prospects
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Metformin and the more potent related compound Phenformin activate AMPK in cells”
§ Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation > Cellular Metabolism and Human Cancer
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
It may state two separate claims as one.
In the paper
“the widely used diabetes drug metformin may offer a possible benefit in cancer prevention as well as improved outcomes when used with other cancer therapies (44)”
§ Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation > Cellular Metabolism and Human Cancer
What the sources say
- Not checked yetcites [44] Evans JM Donnelly LA Emslie-Smith AM Alessi DR Morris AD BMJ 330 1304 2005 15849206 PMC558205
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“a large fraction of human cancer is dependent on aberrant signaling through the PI3K/Akt pathway”
§ Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation > Cellular Metabolism and Human Cancer
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
The paper relies on this without support.
For most mammalian cells in culture, glucose and glutamine are the only two molecules catabolized in appreciable quantities.
“For most mammalian cells in culture, the only two molecules catabolized in appreciable quantities are glucose and glutamine.”
The paper relies on this without support.
Nutrients are not limiting for most proliferating cells.
“For most proliferating cells, nutrients are not limiting so there is no selective pressure to optimize metabolism for ATP yield.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source doesn’t support the claim as written.
In the citing paper
“high levels of ROS generated by ongoing aerobic glycolysis followed by pyruvate oxidation in mitochondria (the Warburg effect), increase receptor and oncogene activity, and the stimulation of growth factor-dependent pathways or oxidizing enzymes induce genetic instability3,4.”
From ROS in cancer therapy: the bright side of the moon (2020) · cites this paper as [3]
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“As a result, the metabolic phenotype of immortalized cell lines may diverge from the native metabolic profile of their tissue of origin (Vander Heiden et al. 2009;Liberti and Locasale 2016).”
From Primary cell cultures versus immortalized cell lines: critical comparative insights into biological fidelity and translational applications (2026) · cites this paper as Vander Heiden et al. 2009
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Moreover, the augmentation of aerobic glycolysis could aid in the mitigation of reactive oxygen species and additionally facilitate the production of a greater quantity of amino acids to support protein synthesis in osteoblasts [58].”
From Mesenchymal stromal cells in bone marrow niche of patients with multiple myeloma: a double-edged sword (2025) · cites this paper as [58]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The ATP that is necessary for fungal cell growth and function is synthesized mainly through oxidative phosphorylation (OXPHOS), with the key enzyme being F1Fo-ATP synthase4.”
From The δ subunit of F1Fo-ATP synthase is required for pathogenicity of Candida albicans (2021) · cites this paper as [4]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“PI3K signaling may be central to linking the common genetic perturbations of cancer, such as RTK mutations and PTEN loss, with altered metabolic processes, including the “lipogenic phenotype” common to many cancers, including GBM (13, 14, 17, 20).”
From An LXR Agonist Promotes Glioblastoma Cell Death through Inhibition of an EGFR/AKT/SREBP-1/LDLR–Dependent Pathway (2011) · cites this paper as [17]
Experimental — accuracy not yet measured
The cited source says what the claim attributes to it.
In the citing paper
“This metabolic reprogramming supports rapid and sustained proliferation by generating ATP, maintaining redox homeostasis, and diverting glycolytic intermediates into biosynthetic pathways required for macromolecular synthesis (Vander Heiden et al. 2009;Liberti and Locasale 2016).”
From Primary cell cultures versus immortalized cell lines: critical comparative insights into biological fidelity and translational applications (2026) · cites this paper as Vander Heiden et al. 2009
The cited source says what the claim attributes to it.
In the citing paper
“In addition to these transcriptional and epigenetic concerns, CR may also influence the underlying metabolic state of primary cells, as sustained proliferation is generally associated with changes in growth-and survival-related signaling, biosynthetic demand, oxidative state, and energy use (Vander Heiden et al. 2009;Hoxhaj and Manning 2020).”
From Primary cell cultures versus immortalized cell lines: critical comparative insights into biological fidelity and translational applications (2026) · cites this paper as Vander Heiden et al. 2009
The cited source says what the claim attributes to it.
In the citing paper
“Furthermore, tumor suppressor pathways such as p53 and LKB1/ AMPK signaling also regulate cellular metabolism (Vander Heiden et al., 2009).”
From Therapeutic targeting of hypoxia and hypoxia-inducible factors in cancer (2016) · cites this paper as Vander Heiden et al., 2009
The cited source says what the claim attributes to it.
In the citing paper
“Cancer cells preferentially metabolize glucose by aerobic glycolysis, a phenomenon known as the Warburg effect.”
From An LXR Agonist Promotes Glioblastoma Cell Death through Inhibition of an EGFR/AKT/SREBP-1/LDLR–Dependent Pathway (2011) · cites this paper as [17]
The cited source says what the claim attributes to it.
In the citing paper
“Similar to gene expression changes, clustering analysis of proteins with temporal expression dynamics similar to gene expression changes reveals that electron transport chain proteins are downregulated in the first 3 days of reprogramming before a gradual metabolic switch to glycolysis, a characteristic that is typically seen in rapidly proliferating cells 84,97 .”
From Mechanisms, pathways and strategies for rejuvenation through epigenetic reprogramming (2023) · cites this paper as [97]
In the citing paper
“The Warburg effect, a preference for glycolysis and lactate secretion in the presence of oxygen, is an example of a metabolic property under cell-autonomous control by oncogenes in many proliferating cancer cells and tumors (1).”
From Metabolic reprogramming and cancer progression (2020) · cites this paper as [1]
In the citing paper
“In 1924, Otto Warburg discovered that cancer cells metabolize glucose differently than cells of normal tissues: that even in conditions of sufficient oxygen availability, cancer cells convert glucose into lactate instead of using glucose for OXPHOS (208).”
From Metabolic Flexibility as an Adaptation to Energy Resources and Requirements in Health and Disease (2018) · cites this paper as [208]
In the citing paper
“The carbon economy of a proliferating cell differs dramatically from that of a cell that is quiescent”
From The emerging hallmarks of cancer metabolism (2016) · cites this paper as Vander Heiden et al., 2009
In the citing paper
“In healthy tissue, the fate of pyruvate is dependent on oxygen availability and mitochondrial respiratory capacity.14”
From The multifaceted contributions of mitochondria to cellular metabolism (2018) · cites this paper as [14]
In the citing paper
“Otto Warburg observed that cancer cells rewire glucose metabolism for lactate synthesis even in normoxia, known as the Warburg Effect.14,21”
From The multifaceted contributions of mitochondria to cellular metabolism (2018) · cites this paper as [14]
In the citing paper
“The recent resurgence of interest in the Warburg hypothesis and cancer energetics (66) emphasizes the dependence of many cancers on glycolysis for energy, creating a high requirement for glucose (or even “glucose addiction”), since ATP generation by glycolysis requires far more glucose than oxidative phosphorylation.”
From Diabetes and Cancer (2010) · cites this paper as [66]
In the citing paper
“This process, also known as the Warburg effect from earlier work in cancer biology, is a common trait of actively proliferating cells (5).”
From Fueling Immunity: Insights into Metabolism and Lymphocyte Function (2013) · cites this paper as [5]
Citations
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Yan, H., Parsons, D. W., Jin, G., McLendon, R., Rasheed, B. A., Yuan, W., Kos, I., Batinic-Haberle, I., Jones, S., Riggins, G. J., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0808710 · Cited by 5,847
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The Biology of Cancer: Metabolic Reprogramming Fuels Cell Growth and Proliferation
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The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth
Christofk, H. R., Vander Heiden, M. G., Harris, M. H., Ramanathan, A., Gerszten, R. E., Wei, R., Fleming, M. D., Schreiber, S. L., & Cantley, L. C. (2008) · Nature · doi:10.1038/nature06734 · Cited by 2,820
Self-citation
Research works printed but not linked: 2
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- Sonveaux P., et al.., J. Clin. Invest. 118, 3930 (2008).Medline
Cited by
Sorted by citations
Hallmarks of Cancer: The Next Generation
Hanahan, D., & Weinberg, R. A. (2011) · Cell · doi:10.1016/j.cell.2011.02.013 · Cited by 66,590
Vogelstein, B., Papadopoulos, N., Velculescu, V. E., Zhou, S., Diaz, L. A., & Kinzler, K. W. (2013) · Science · doi:10.1126/science.1235122 · Cited by 7,863
The emerging hallmarks of cancer metabolism
Pavlova, N. N., & Thompson, C. B. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2015.12.006 · Cited by 5,926
Self-citationThe Warburg Effect: How Does it Benefit Cancer Cells?
Liberti, M. V., & Locasale, J. W. (2016) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2015.12.001 · Cited by 5,150
Regulation of cancer cell metabolism
Cairns, R. A., Harris, I. S., & Mak, T. W. (2011) · Nature Reviews Cancer · doi:10.1038/nrc2981 · Cited by 4,744
Metadata
- Authors
- Vander Heiden, M. G., Cantley, L. C., & Thompson, C. B.
- Affiliations
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
- Harvard University (US)
- Abramson Cancer Center (US)
- Corresponding author
- Cantley, Lewis C.
- Thompson, Craig B.
- Venue
- Science
- Published
- 2009-05-22
- Volume
- 324
- Issue
- 5930
- Pages
- 1029-1033
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC2849637
- OpenAlex
- W2097259163
- Semantic Scholar
- 5a3b09333eb2968904933e726dc29625e10eb188
- Cited by
- 16,197
- References
- 47
- Citations by year
- 2026: 969 · 2025: 1224 · 2024: 1225 · 2023: 1156 · 2022: 1351 · 2021: 1439 · 2020: 1276 · 2019: 1065 · 2018: 1028 · 2017: 1027 · 2016: 921 · 2015: 823 · 2014: 727 · 2013: 665 · 2012: 535
- FWCI
- 27.05
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (R01CA092660, R01CA105463, T32CA009172)
- National Institute of General Medical Sciences (R01GM056203)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer and biochemical research
- Keywords
- Warburg effect, aerobic glycolysis, cancer metabolism, cell proliferation, mitochondrial oxidative phosphorylation, ATP production, signaling pathways, cancer-associated mutations, growth regulation
- MeSH terms
- Adenosine Triphosphate, Aerobiosis, Amino Acids, Animals, Glucose, Glycolysis, Humans, Lipids, Mutation, Neoplasms, Nucleotides, Oxidative Phosphorylation, Signal Transduction, Cell Proliferation, Metabolic Networks and Pathways
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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