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Cited by 2,740Cancer, Hypoxia, and MetabolismMetabolism, Diabetes, and CancerCancer, Lipids, and Metabolism

Metabolic reprogramming and cancer progression

Open access
Faubert, Brandon, Solmonson, Ashley, DeBerardinis, Ralph J.·2020·Science
DOI 10.1126/science.aaw5473PMC PMC7227780
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Abstract

Metabolism as cancer progresses: Numerous cancer-specific alterations in metabolism have been identified but have not yet resulted in an effective anti cancer therapeutic. In a Review, Faubert et al. discuss how metabolism changes as cancer develops from a small, premalignant lesion to an aggressive primary tumor and then metastasizes. Metabolic vulnerabilities likely change with cancer progression, making the identification of general cancer-associated metabolic features difficult. The authors propose that a more targeted approach to tissues and vulnerabilities identified in patients may be more effective. Science , this issue p. eaaw5473

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Crossref · 10.1126/science.aaw5473

Cites

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Claims the paper makes

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  • Premisecitation

    Metabolic reprogramming precedes liver cancer in mice with MYC expression in hepatocytes.

    “Metabolic reprogramming precedes liver cancer in mice with MYC expression in hepatocytes (23).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
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      Not checked in the free run.

  • Premisecitation

    IDH1 and IDH2 mutations generate D-2HG, which inhibits epigenetic enzymes including histone demethylases and TET family hydroxylases.

    “Mutations in isocitrate dehydrogenase isoform-1 (IDH1) and IDH2 generate the oncometabolite D-2-hydroxyglutarate (D-2HG), which inhibits epigenetic enzymes including histone demethylases and the Ten-eleven translocation (TET) family of 5-methylcytosine hydroxylases.”
    Quote in the paperSubstantial claim0 of 1 sources checked
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  • Premisenone given

    The time between metastatic cells reaching a distant organ and the appearance of macrometastasis varies widely.

    “The dormancy period between arrival of metastatic cells in a distant organ and appearance of macrometastasis varies widely.”
    Quote in the paperSubstantial claim
  • Premisecitation

    Despite ubiquitous SDH expression, germline mutations in SDH subunits cause cancer only at a few sites, including paraganglioma, pheochromocytoma, and gastrointestinal stromal tumors.

    “Despite ubiquitous expression of the metabolic enzyme succinate dehydrogenase (SDH), germline mutations in subunits of this complex cause cancer only in a few sites, including neuroendocrine tissues (paraganglioma), the adrenal gland (pheochromocytoma), and the stomach and small intestine (gastrointestinal stromal tumors) (8–10).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
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  • Premisereasoning

    Human tumors are metabolically heterogeneous.

    “Second, as the approaches used to assess metabolic phenotypes have become more informative, it has become clear that human tumors are metabolically heterogeneous.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [2] Kim J, DeBerardinis RJ, Mechanisms and implications of metabolic heterogeneity in cancer. Cell Metab. 30, 434– 446 (2019). doi: 10.1016/j.cmet.2019.08.013 31484055 PMC6730674 source

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    Premisecitation

    Oncogenic KRas increases acetyl-CoA and ROS before ADM develops, and inhibiting these phenotypes blocks ADM.

    “Oncogenic KRas increases the levels of acetyl coenzyme A (CoA) and reactive oxygen species (ROS) before the development of ADM, and inhibiting these phenotypes blocks ADM (19, 20).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
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      Not checked in the free run.

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    Premisecitation

    Me4FDG is taken up by SGLT and can identify AAH and low-grade adenocarcinomas of the lung.

    “But an alternative tracer, methyl-4-deoxy-4-[18F]-fluoro-α-d-glucopyranoside (Me4FDG), is taken up by SGLT and can identify AAH and low-grade adenocarcinomas of the lung (24).”
    Quote in the paperSubstantial claim0 of 1 sources checked
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      Not checked in the free run.

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    Interpretationreasoning

    Pathways that drive growth of localized, treatment-naive tumors are distinct from, and sometimes irrelevant to, the activities that cause mortality by supporting metastasis and therapy resistance.

    “A major theme arising from recent research is that pathways that stimulate the growth of localized, treatment-naïve tumors are distinct from and in some cases irrelevant to the activities that drive mortality by supporting metastasis and therapy resistance.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    A large prospective analysis of more than 900,000 Americans found greater than a 50% increase in cancer mortality among patients with the highest body mass index.

    “Many epidemiological studies report associations between obesity and cancer, and a large prospective analysis of more than 900,000 Americans found greater than a 50% increase in cancer mortality in patients with the highest body mass index (15, 16).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
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      Not checked in the free run.

  • May combine two claims.

    Premisereasoning

    SGLT2 does not transport FDG, so AAH lesions are poor candidates for FDG-PET imaging.

    “SGLT2 does not transport the common cancer imaging tracer 18fluoro-2-deoxyglucose (FDG), and thus, these lesions are poor candidates for FDG-PET (positron emission tomography) imaging.”
    Quote in the paperSubstantial claim

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    Interpretationreasoning

    Factors in the microenvironment and genetic changes create selective pressures that drive clonal evolution within tumors, and this process can create or remove metabolic liabilities while helping cancer progress.

    “Microenvironmental and genetic factors appear to induce selective pressures that drive clonal evolution within tumors, and this can create or eliminate metabolic liabilities while facilitating cancer progression.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    These studies demonstrate the functional and therapeutic relevance of metabolic reprogramming early in tumorigenesis.

    “These studies demonstrate the functional and therapeutic relevance of metabolic reprogramming early in tumorigenesis.”
    Quote in the paperSubstantial claim

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    Premisecitation

    Silencing Bcat1 reduces leukemia initiation, and overexpressing it promotes NRas-driven leukemia initiation even in cells lacking Ezh2 mutations.

    “Silencing Bcat1 reduces leukemia initiation, and overexpressing this enzyme promotes NRas-driven leukemia initiation even in cells that lack Ezh2 mutations (28).”
    Quote in the paperSubstantial claim0 of 1 sources checked
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    Premisecitation

    Metabolic changes occur in premalignant colonic polyps in humans and mice, and some are retained in adenocarcinomas.

    “Other studies in humans and mice report metabolic changes in premalignant colonic polyps, some of which are retained in adenocarcinomas (21, 22).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [21] Backshall A, Detection of metabolic alterations in non-tumor gastrointestinal tissue of the Apc(Min/+) mouse by (1) H MAS NMR spectroscopy. J. Proteome Res. 8, 1423– 1430 (2009). doi: 10.1021/pr800793w 19159281 source

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      Not checked in the free run.

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    Premisecitation

    In early premalignant liver, MYC drives enhanced conversion of pyruvate to alanine, while later malignant lesions convert pyruvate to lactate.

    “In early-stage, premalignant liver, MYC drives enhanced conversion of pyruvate to alanine, whereas later-stage malignant lesions convert pyruvate to lactate.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [23] Hu S, 13C-pyruvate imaging reveals alterations in glycolysis that precede c-Myc-induced tumor formation and regression. Cell Metab. 14, 131– 142 (2011). doi: 10.1016/j.cmet.2011.04.012 21723511 PMC3858338 source

      Not checked in the free run.

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    Premisecitation

    Diabetes increases the frequency of KRAS variants in human pancreas, possibly through chronic hyperglycemia effects on nucleotide balance.

    “Diabetes increases the frequency of KRAS variants in human pancreas, possibly through the effects of chronic hyperglycemia on nucleotide balance (17).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
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  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationnone given

    The current view of cancer metabolism is that it is flexible and context-specific, with few fixed liabilities that apply broadly.

    “The emerging view of cancer metabolism is that it is flexible and context-specific, with few fixed, broadly applicable liabilities.”
    Quote in the paperNot a substantial claim

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    Premisecitation

    Transgenic MYC causes metabolic changes in both liver and lung tumors in mice, but it activates glutamine catabolism in lung tumors and glutamine synthesis in liver tumors.

    “Transgenic MYC induces metabolic changes in both liver tumors and lung tumors but activates glutamine catabolism in lung tumors and glutamine synthesis in liver tumors.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [5] Yuneva MO, The metabolic profile of tumors depends on both the responsible genetic lesion and tissue type. Cell Metab. 15, 157– 170 (2012). doi: 10.1016/j.cmet.2011.12.015 22326218 PMC3282107 source

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    Premisecitation

    Detailed molecular analysis of CCPAP found a low genomic burden of point mutations and copy-number variants, no recurrent nonsynonymous mutations, and a DNA methylation pattern resembling nonmalignant kidney.

    “Nevertheless, a detailed molecular analysis revealed a low genomic burden of point mutations and copy-number variants, no recurrent nonsynonymous mutations, and a DNA methylation pattern that resembles the nonmalignant kidney.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [13] Xu J, Abnormal oxidative metabolism in a quiet genomic background underlies clear cell papillary renal cell carcinoma. eLife 8, e38986 (2019). doi: 10.7554/eLife.38986 30924768 PMC6459676 source

      Not checked in the free run.

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    Premisecitation

    CCPAP tumors have metabolomic signatures suggesting oxidative stress, suppressed oxidative metabolism, and depletion of mitochondrial DNA and RNA.

    “These tumors bear metabolomic signatures that suggest oxidative stress, suppressed oxidative metabolism, and depletion of mitochondrial DNA and RNA.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [13] Xu J, Abnormal oxidative metabolism in a quiet genomic background underlies clear cell papillary renal cell carcinoma. eLife 8, e38986 (2019). doi: 10.7554/eLife.38986 30924768 PMC6459676 source

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    Premisecitation

    A low-carbohydrate, ketogenic diet blunts the hyperglycemia and insulin release that accompany PI3K inhibition and improves the efficacy of PI3K inhibitors on tumor growth in mice.

    “Placing mice on a low-carbohydrate, ketogenic diet blunts the hyperglycemia and insulin release that accompany PI3K inhibition, and this improves the efficacy of PI3K inhibitors on tumor growth (113).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [113] Hopkins BD, Suppression of insulin feedback enhances the efficacy of PI3K inhibitors. Nature 560, 499– 503 (2018). doi: 10.1038/s41586-018-0343-4 30051890 PMC6197057 source

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    Premisecitation

    Recently described OXPHOS inhibitors display enhanced toxicity against cultured cancer cells compared with nontransformed cells or other cancer cells that can compensate for OXPHOS impairment, and they suppress growth of susceptible tumors in mice at doses well tolerated over the short term.

    “Recently described OXPHOS inhibitors display enhanced toxicity against cultured cancer cells compared with either nontransformed cells or other cancer cells with metabolic properties that allow them to compensate for OXPHOS impairment (116, 117). It is encouraging that these agents also suppress growth of susceptible tumors in mice, using doses that are well-tolerated over the short term.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [116] Molina JR, An inhibitor of oxidative phosphorylation exploits cancer vulnerability. Nat. Med. 24, 1036– 1046 (2018). doi: 10.1038/s41591-018-0052-4 29892070 source

      Not checked in the free run.

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    Premisecitation

    In human prostate cancer, tumor grade correlates with MCT1 expression and with imaging of 13C-lactate after injection of hyperpolarized 13C-pyruvate.

    “In human prostate cancer, tumor grade correlates with MCT1 expression and with imaging of 13C-lactate after injection of hyperpolarized 13C-pyruvate (122).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [122] Granlund KL, Hyperpolarized MRI of human prostate cancer reveals increased lactate with tumor grade driven by monocarboxylate transporter 1. Cell Metab. 31, 105– 114.e3 (2020). doi: 10.1016/j.cmet.2019.08.024 31564440 PMC6949382 source

      Not checked in the free run.

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    Premisecitation

    PI3K inhibitors suppress glucose uptake by muscle and other tissues, causing elevated blood glucose and pancreatic insulin release; the insulin surge reactivates PI3K signaling in the tumor and limits the efficacy of PI3K inhibitors on tumor growth.

    “PI3K inhibitors suppress glucose uptake by the muscle and other tissues, resulting in elevated blood glucose and pancreatic insulin release after administration of the drug. The insulin surge reactivates PI3K signaling in the tumor, limiting the efficacy of PI3K inhibitors on tumor growth.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [113] Hopkins BD, Suppression of insulin feedback enhances the efficacy of PI3K inhibitors. Nature 560, 499– 503 (2018). doi: 10.1038/s41586-018-0343-4 30051890 PMC6197057 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationnone given

    Evidence indicates that metabolic phenotypes evolve as cancer progresses, with new dependencies emerging in the context of therapy resistance and metastasis.

    “Evidence also indicates that metabolic phenotypes evolve as cancer progresses, with new dependencies emerging in the context of therapy resistance and metastasis.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisereasoning

    Glutamine addiction is a common feature of cultured cancer cells, and early attempts to target this pathway in vivo used the glutamine analog DON, which kills cancer cells but is unacceptably toxic to the gastrointestinal tract and other tissues, limiting its clinical development.

    “Glutamine addiction is a common feature of cultured cancer cells, and early attempts to target this pathway in vivo used the glutamine analog 6-diazo-5-oxo-l-norleucine (DON). By inhibiting a myriad of enzymes that use glutamine as a substrate, DON kills cancer cells but is unacceptably toxic to the gastrointestinal tract and other tissues, limiting its clinical development.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Glutamine addiction is a common feature of cultured cancer cells.

  • May combine two claims.

    Interpretationreasoning

    Cancer cell metabolism is flexible and heterogeneous.

    “The insights reviewed above indicate that cancer cell metabolism is flexible and heterogeneous”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    OXPHOS promotes resistance to cytarabine in mouse models of AML; cytarabine treatment spares cells with high OXPHOS, and cytarabine-resistant cells are susceptible to OXPHOS inhibitors.

    “OXPHOS also promotes resistance to the antimetabolite cytarabine in mouse models of AML (115). Cells persisting after cytarabine treatment and preexisting cells with innate cytarabine resistance both displayed enhanced OXPHOS. Cytarabine treatment in AML-bearing mice spares cells with high levels of OXPHOS, and cytarabine-resistant cells are susceptible to OXPHOS inhibitors (115).”
    Quote in the paperSubstantial claim0 of 1 sources checked
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      Not checked in the free run.

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    Premisecitation

    A new PET probe, 18F-BnTP, accumulates in tumors in proportion to their reliance on OXPHOS, and in mouse models of lung cancer 18F-BnTP imaging predicts sensitivity to OXPHOS inhibition regardless of whether the tumors take up 18FDG.

    “A new probe, 4-[18F]fluorobenzyl-triphenylphosphonium (18F-BnTP), accumulates in tumors in proportion to their reliance on OXPHOS (123). In mouse models of lung cancer, 18F-BnTP imaging predicts sensitivity to OXPHOS inhibition, regardless of whether or not the tumors take up 18FDG.”
    Quote in the paperSubstantial claim0 of 1 sources checked
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      Not checked in the free run.

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    Premisecitation

    2-HG accumulation in IDH1- and IDH2-mutant tumors is a rare example in which the metabolite directly reports the oncogenic driver and potential therapy, and proton magnetic resonance spectroscopy can noninvasively track 2-HG abundance in IDH-mutant gliomas, predicting disease progression and response to therapy through longitudinal measurements.

    “First, 2-HG accumulation in IDH1- and IDH2-mutant tumors is a rare example in which the metabolite directly reports the oncogenic driver and potential therapy (Fig. 4). Proton magnetic resonance spectroscopy can noninvasively track 2-HG abundance in IDH-mutant gliomas, predicting both disease progression and response to therapy through longitudinal 2-HG measurements (120).”
    Quote in the paperSubstantial claim0 of 1 sources checked
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      Not checked in the free run.

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    Premisecitation

    Lactate export by non-small-cell lung cancer cells induces neighboring fibroblasts to secrete hepatocyte growth factor, which activates c-MET on cancer cells and sustains oncogenic signaling despite EGFR inhibitors.

    “Lactate export by the cancer cells induces neighboring fibroblasts to secrete hepatocyte growth factor, which activates its receptor tyrosine kinase c-MET on cancer cells. Consequently, the cancer cells sustain oncogenic signaling even in the presence of EGFR inhibitors (111).”
    Quote in the paperSubstantial claim0 of 1 sources checked
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      Not checked in the free run.

  • May combine two claims.

    Premisenone given

    Clinical efficacy of mutant IDH1 and IDH2 inhibitors has been demonstrated in AML patients, and clinical trials in solid tumors are under way.

    “Clinical efficacy of mutant IDH1 and −2 inhibitors has been demonstrated in AML patients, with clinical trials in solid tumors now under way.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    In chronic lymphocytic leukemia, acquired resistance to venetoclax involves increased mitochondrial mass and enhanced OXPHOS, and inhibiting OXPHOS increases venetoclax sensitivity in culture and in vivo.

    “In chronic lymphocytic leukemia, acquired resistance to venetoclax–an inhibitor of the antiapoptotic protein B cell lymphoma-2 (BCL-2)–involves increased mitochondrial mass and enhanced OXPHOS (114). Inhibiting OXPHOS increases venetoclax sensitivity in culture and in vivo.”
    Quote in the paperSubstantial claim0 of 1 sources checked
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      Not checked in the free run.

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Interpretationnone given

    Recent work in cancer metabolism has focused on assessing metabolic phenotypes in native microenvironments in humans and mice, producing a greater appreciation for metabolic heterogeneity among tumors and expanding the scope of metabolic dependencies beyond classical pathways that dominate metabolism in culture.

    “Recent work in cancer metabolism has focused on assessing metabolic phenotypes in native microenvironments in humans and mice. This has produced a greater appreciation for metabolic heterogeneity among tumors, expanding the scope of metabolic dependencies beyond the classical pathways that dominate metabolism in culture.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisenone given

    Most metabolic therapies lack biomarkers, and conventional molecular analyses such as DNA and RNA sequencing are usually inadequate surrogates for metabolism.

    “However, most metabolic therapies lack biomarkers, and conventional molecular analyses such as DNA and RNA sequencing usually prove to be inadequate surrogates for metabolism.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Conventional molecular analyses such as DNA and RNA sequencing are inadequate surrogates for metabolism.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationreasoning

    Once dormant cells begin to proliferate, anabolic pathways involving biomass assimilation are presumably activated to support progression to macrometastasis.

    “Once dormant cells begin to proliferate, anabolic pathways involving biomass assimilation are presumably activated to support progression to macrometastasis (Fig. 3).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    D-2HG inhibits canonical metabolic enzymes, including transaminases that produce glutamate for glutathione biosynthesis, rendering IDH-mutant gliomas susceptible to treatments that deplete glutamate and enhance oxidative stress.

    “In addition to its epigenetic effects, D-2HG inhibits enzymes from the canonical metabolic network (104). Such enzymes include transaminases that produce glutamate for glutathione biosynthesis, rendering IDH-mutant gliomas susceptible to treatments that deplete glutamate and enhance oxidative stress (105).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [104] Lu C, IDH mutation impairs histone demethylation and results in a block to cell differentiation. Nature 483, 474– 478 (2012). doi: 10.1038/nature10860 22343901 PMC3478770 source

      Not checked in the free run.

    • cites [105] McBrayer SK, Transaminase inhibition by 2-hydroxyglutarate impairs glutamate biosynthesis and redox homeostasis in glioma. Cell 175, 101– 116.e25 (2018). doi: 10.1016/j.cell.2018.08.038 30220459 PMC6219629 source

      Not checked in the free run.

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    Premisecitation

    FH and SDH mutations create truncal metabolic aberrations, induce permanent restructuring of the TCA cycle, and result in numerous metabolic liabilities in preclinical models.

    “FH and SDH mutations also create truncal metabolic aberrations. These mutations induce permanent restructuring of the TCA cycle and result in numerous metabolic liabilities in preclinical models (106–108).”
    Quote in the paperSubstantial claim0 of 3 sources checked
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      Not checked in the free run.

    • cites [107] Lussey-Lepoutre C, Loss of succinate dehydrogenase activity results in dependency on pyruvate carboxylation for cellular anabolism. Nat. Commun. 6, 8784 (2015). doi: 10.1038/ncomms9784 26522426 PMC4632646 source

      Not checked in the free run.

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      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Intravenous infusion of 13C-lactate into human non-small-cell lung cancer patients and mice bearing patient-derived melanomas identified tumors with a propensity for future metastasis, which required MCT1-dependent lactate transport in the mice.

    “Intravenous infusion of 13C-lactate into human non-small-cell lung cancer patients and mice bearing patient-derived melanomas identified tumors with a propensity for future metastasis, which required MCT1-dependent lactate transport in the mice (58, 100).”
    Quote in the paperSubstantial claim0 of 2 sources checked
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      Not checked in the free run.

    • cites [100] Tasdogan A, Metabolic heterogeneity confers differences in melanoma metastatic potential. Nature 577, 115– 120 (2020). doi: 10.1038/s41586-019-1847-2 31853067 PMC6930341 source

      Not checked in the free run.

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  • The paper relies on this without support.

    Death from cancer is determined largely by metastasis rather than by localized growth of the primary tumor.

    “Death from cancer is determined largely by metastasis rather than localized tumor growth at the primary site.”

  • The paper relies on this without support.

    Metabolic reprogramming is a hallmark of malignancy.

    “Metabolic reprogramming is a hallmark of malignancy first recognized a century ago.”

  • The paper relies on this without support.

    Tumor cells require many of the same pathways and adaptations available to nonmalignant tissues, so few metabolic activities are truly confined to tumors.

    “First, tumor cells require many of the same pathways and adaptations available to nonmalignant tissues, indicating that few metabolic activities are truly confined to tumors.”

  • The paper relies on this without support.

    Glutamine addiction is a common feature of cultured cancer cells.

    “Glutamine addiction is a common feature of cultured cancer cells”

  • The paper relies on this without support.

    Conventional molecular analyses such as DNA and RNA sequencing are inadequate surrogates for metabolism.

    “conventional molecular analyses such as DNA and RNA sequencing usually prove to be inadequate surrogates for metabolism.”
5 of 5

Claims other papers make about this one

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  • Loss of LKB1 sustains KRAS-mediated proliferation through autophagy and increased synthesis of essential macromolecules under nutrient deprivation.

    “This could be explained by the fact that loss of LKB1 sustains KRAS-mediated proliferation through autophagy and increased synthesis of essential macromolecules, even under nutrient-deprived conditions68.”

    From The metabolic landscape of RAS-driven cancers from biology to therapy (2021) · cites this paper as [68]

  • The two hallmarks exhibit commonalities but also differences or antagonisms between aging-associated deregulated nutrient sensing and cancer-associated deregulation of cellular energy metabolism.

    “Both hallmarks exhibit clear commonalities, but there are also some differences or even antagonisms between aging-associated deregulated nutrient sensing and cancer-associated deregulation of cellular energy metabolism.[204][205][206]”

    From Meta-hallmarks of aging and cancer (2023) · cites this paper as [205]

  • In non-transformed cells of well-oxygenated tissues and even in tumor cells located near blood vessels, an oxidative phenotype with reverse utilization of lactic acid (reverse Warburg effect) can be observed.

    “In non-transformed cells of well-oxygenated tissues and even in tumor cells which are located near to blood vessels, an oxidative phenotype, the reverse utilization of lactic acid (reverse Warburg effect) can be observed [36].”

    From Hypoxia Signaling in Cancer: From Basics to Clinical Practice (2021) · cites this paper as [36]

Cites

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Related

Authors
Faubert, B., Solmonson, A., & DeBerardinis, R. J.
Affiliations
Children's Medical Center (US)
Corresponding author
  • Faubert, Brandon
  • Solmonson, Ashley
  • DeBerardinis, Ralph J.
ORCID
Venue
Science
Publisher
American Association for the Advancement of Science (AAAS)
Published
2020-04-10
Volume
368
Issue
6487
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
DOI
10.1126/science.aaw5473
PMC
PMC7227780
OpenAlex
W3015450697
Semantic Scholar
3290d4791010bd52ce6a6e7fd0cd47eb3758c274
Cited by
2,740
References
128
Citations by year
2026: 539 · 2025: 664 · 2024: 475 · 2023: 386 · 2022: 370 · 2021: 241 · 2020: 65
FWCI
27.41
Type
journal article
Language
en
Open access
Locations
  • Science (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Cancer Institute (R35 CA220449)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (F32HD096786)
  • Canadian HIV Trials Network, Canadian Institutes of Health Research ((MFE140911)
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 › Cancer Research › Cancer, Lipids, and Metabolism
Keywords
metabolic reprogramming, cancer metabolism, tumor progression, metabolic heterogeneity, metastasis, primary tumor, cancer therapy
MeSH terms
Animals, Humans, Neoplasm Invasiveness, Neoplasm Metastasis, Neoplasms, Precancerous Conditions, Disease Progression, Mice, Molecular Targeted Therapy

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.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-06.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-06.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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