Reductive glutamine metabolism by IDH1 mediates lipogenesis under hypoxia
Open accessAbstract
Acetyl coenzyme A (AcCoA) is the central biosynthetic precursor for fatty-acid synthesis and protein acetylation. In the conventional view of mammalian cell metabolism, AcCoA is primarily generated from glucose-derived pyruvate through the citrate shuttle and ATP citrate lyase in the cytosol. However, proliferating cells that exhibit aerobic glycolysis and those exposed to hypoxia convert glucose to lactate at near-stoichiometric levels, directing glucose carbon away from the tricarboxylic acid cycle and fatty-acid synthesis. Although glutamine is consumed at levels exceeding that required for nitrogen biosynthesis, the regulation and use of glutamine metabolism in hypoxic cells is not well understood. Here we show that human cells use reductive metabolism of α-ketoglutarate to synthesize AcCoA for lipid synthesis. This isocitrate dehydrogenase-1 (IDH1)-dependent pathway is active in most cell lines under normal culture conditions, but cells grown under hypoxia rely almost exclusively on the reductive carboxylation of glutamine-derived α-ketoglutarate for de novo lipogenesis. Furthermore, renal cell lines deficient in the von Hippel-Lindau tumour suppressor protein preferentially use reductive glutamine metabolism for lipid biosynthesis even at normal oxygen levels. These results identify a critical role for oxygen in regulating carbon use to produce AcCoA and support lipid synthesis in mammalian cells.
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Both HIF-1α and HIF-2α activation upregulates the glutamine transporter SLC38A2, increasing glutamine dependency and correlating with worse survival in breast cancer patients.
“Both HIF-1α and HIF-2α activation promotes the upregulation of the glutamine transporter, SLC38A2, which increases the dependency of cells to glutamine and correlates with poorer survival in patients with breast cancer [58]”
From The HIF Axes in Cancer - Angiogenesis, Metabolism and Immune-Modulation (2025) · cites this paper as [58]
The paper’s main text (indexed under Abstract; page unavailable) reports that hypoxia increases some cells’ dependence on glutamine and discusses HIF involvement in a switch to reductive glutamine metabolism. It does not report HIF-1α or HIF-2α upregulating SLC38A2, or an association with survival in breast cancer patients. (LLM, conf=0.88)
Experimental — accuracy not yet measuredCHK1 inhibitors and glutaminase inhibitors are considered potential candidates for treating Myc-overexpressing cancers.
“Similarly, checkpoint kinase 1 (CHK1) inhibitors625–627 and glutaminase (GLS) inhibitors628–634 are also considered potential candidates for treating Myc-overexpressing cancers.”
From Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials (2023) · cites this paper as [631]
Citrate generated by reductive carboxylation of α-KG is crucial for lipid synthesis under low-oxygen conditions.
“Citrate, generated by reductive carboxylation of α-KG, is especially crucial for lipid synthesis under low-oxygen conditions24,25.”
From Glutamine reliance in cell metabolism (2020) · cites this paper as [24]
Hypoxia switches the fate of glutamine from the oxidative pathway into the reductive carboxylation pathway.
“and switch the fate of glutamine from the oxidative pathway into the reductive carboxylation pathway24.”
From Glutamine reliance in cell metabolism (2020) · cites this paper as [24]
In the context of constitutive HIF-2α stabilization or defective mitochondrial electron transport chain, glutamine-derived α-KG is reductively carboxylated through consumption of NADPH by IDH2 to generate citrate.
“In the context of constitutive HIF-2α stabilization75 or a defective mitochondrial electron transport chain76, glutamine-derived α-KG is reductively carboxylated through the consumption of NADPH by IDH2 to generate citrate.”
From Glutamine reliance in cell metabolism (2020) · cites this paper as [75]
Glutamine acts as an alternative fuel for fatty acid synthesis, supplying citrate via mitochondrial reductive carboxylation, especially under hypoxic conditions.
“Glutamine acts as an alternative fuel for fatty acid synthesis, supplying citrate via mitochondrial reductive carboxylation, especially under hypoxic conditions74,75.”
From Glutamine reliance in cell metabolism (2020) · cites this paper as [75]
Proliferating cells under hypoxia predominantly reductively carboxylate glutamine-generated α-ketoglutarate through IDH 1/2 to generate M5 citrate.
“Alternatively, proliferating cells under hypoxia have been reported to predominantly reductively carboxylate glutamine generated α-ketoglutarate through IDH 1/2 to generate M5 citrate (Figure 4A) (Metallo, 2012).”
From Tumor microenvironment derived exosomes pleiotropically modulate cancer cell metabolism (2016) · cites this paper as Metallo, 2012
Reductive carboxylation is a critical pathway to support the growth of tumor cells under hypoxia.
“Previous reports showed that reductive carboxylation is a critical pathway to support the growth of tumor cells under hypoxia (Metallo, 2012; Mullen, 2012).”
From Tumor microenvironment derived exosomes pleiotropically modulate cancer cell metabolism (2016) · cites this paper as Metallo, 2012
Upregulation of the reductive carboxylation pathway enhances cancer cell proliferation.
“The upregulation of the reductive carboxylation pathway enhances cancer cells proliferation (Metallo, 2012; Mullen, 2012; Wise et al., 2011).”
From Tumor microenvironment derived exosomes pleiotropically modulate cancer cell metabolism (2016) · cites this paper as Metallo, 2012
Under conditions of hypoxia or impaired mitochondrial respiration, certain reactions of the TCA cycle reverse to support glutamine-dependent reductive carboxylation.
“For example, under conditions of hypoxia or impaired mitochondrial respiration, certain reactions of the TCA cycle reverse to support glutamine-dependent reductive carboxylation (92, 122, 123).”
From Regulation and function of the mammalian tricarboxylic acid cycle (2023) · cites this paper as [122]
Reductive carboxylation reverses a section of TCA cycle, converting α-ketoglutarate into citrate, which can generate cytosolic acetyl-CoA.
“In a process referred to as reductive carboxylation, a section of the TCA cycle reverses itself, converting α-ketoglutarate into citrate, which can be then used to generate a source of cytosolic acetyl-CoA (Metallo et al., 2012; Wise et al., 2011).”
From The emerging hallmarks of cancer metabolism (2016) · cites this paper as Metallo et al., 2012
Citrate is generated by citrate synthase or through the reduction of α-ketoglutarate by isocitrate dehydrogenase.
“Citrate is generated by citrate synthase (CS) or through the reduction of α-ketoglutarate by isocitrate dehydrogenase (IDH).79–81”
From The multifaceted contributions of mitochondria to cellular metabolism (2018) · cites this paper as [79]
Citrate is generated predominantly from pyruvate-derived AcCoA under normal growth conditions.
“Citrate levels, however, were markedly decreased in Mpc1KD or Mpc2KD (Mpc1/2KD) cells, as this metabolite is generated predominantly from pyruvate-derived AcCoA under normal growth conditions (Metallo et al., 2012).”
From Regulation of Substrate Utilization by the Mitochondrial Pyruvate Carrier (2014) · cites this paper as Metallo et al., 2012
Glutamine can contribute carbon to fatty acid synthesis via reductive carboxylation or oxidative glutaminolysis.
“Glutamine can contribute carbon to fatty acid synthesis via reductive carboxylation or oxidative glutaminolysis.”
From Regulation of Substrate Utilization by the Mitochondrial Pyruvate Carrier (2014) · cites this paper as Metallo et al., 2012
Reductive carboxylation is highly active in cells proliferating under hypoxia or with a compromised respiratory chain, while oxidative glutaminolysis has been observed in B cell lymphoma.
“The former pathway is highly active in cells proliferating under hypoxia or those with a compromised respiratory chain (Metallo et al., 2012; Mullen et al., 2012; Scott et al., 2011; Wise et al., 2011), while the latter pathway has been observed in B cell lymphoma (Le et al., 2012).”
From Regulation of Substrate Utilization by the Mitochondrial Pyruvate Carrier (2014) · cites this paper as Metallo et al., 2012
The switch to reductive versus oxidative metabolism of α-KG is regulated in part by HIF-1α.
“This switch to reductive versus oxidative metabolism of α-KG is regulated in part by HIF-1α (71, 72), although the exact mechanism by which HIF-1α does so remains unclear.”
From Fueling Immunity: Insights into Metabolism and Lymphocyte Function (2013) · cites this paper as [71]
α-KG can be converted to citrate through reductive carboxylation under conditions of stress such as hypoxia or mitochondrial dysfunction.
“Although oxidation of glutamine-derived α-KG in the TCA cycle serves as a minor source of lipogenic acetyl-CoA under normal growth conditions, α-KG can be converted to citrate through reductive carboxylation under conditions of stress such as hypoxia or mitochondrial dysfunction (70–72).”
From Fueling Immunity: Insights into Metabolism and Lymphocyte Function (2013) · cites this paper as [71]
T cells can use reductive glutamine metabolism for fatty acid biosynthesis under hypoxic conditions.
“The work from Metallo and colleagues (71) suggests that T cells can use reductive glutamine metabolism for fatty acid biosynthesis under hypoxic conditions.”
From Fueling Immunity: Insights into Metabolism and Lymphocyte Function (2013) · cites this paper as [71]
These cancers preferentially perform reductive and carboxylating biosynthetic reactions from glutamine carbon in place of oxidative metabolism of both glucose and glutamine.
“In place of oxidative metabolism of both glucose and glutamine, these cancers preferentially perform reductive and carboxylating biosynthetic reactions from glutamine carbon (Le et al., 2012; Metallo et al., 2012; Mullen et al., 2012; Wise et al., 2011).”
From Metabolic Reprogramming: A Cancer Hallmark Even Warburg Did Not Anticipate (2012) · cites this paper as Metallo et al., 2012
IDH-dependent reductive carboxylation plays a particularly important role in proliferating cells that exhibit decreased flux of glucose-derived pyruvate into mitochondria, in hypoxic cells or cells with defects in mitochondrial oxidative phosphorylation.
“Recently three independent reports implicated IDH-dependent reductive carboxylation as playing a particularly important role in proliferating cells that exhibit decreased flux of glucose-derived pyruvate into the mitochondria. This occurs in hypoxic cells or in cells harboring defects in mitochondrial oxidative phosphorylation (Metallo et al., 2012; Mullen et al., 2012; Wise et al., 2011).”
From Metabolic Reprogramming: A Cancer Hallmark Even Warburg Did Not Anticipate (2012) · cites this paper as Metallo et al., 2012
Tumor cells with mutations in the TCA cycle or ETC, or with hypoxia-induced suppression of oxidative metabolism, use reductive carboxylation of α-KG to produce citrate and other precursors during growth.
“tumor cells with mutations in the TCA cycle or ETC (Mullen et al., 2011), or with hypoxia-induced suppression of oxidative metabolism (Metallo et al., 2011; Scott et al., 2011; Wise et al., 2011) use reductive carboxylation of α-KG to produce citrate and other precursors during growth.”
From Cellular Metabolism and Disease: What Do Metabolic Outliers Teach Us? (2012) · cites this paper as Metallo et al., 2011
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Cites
Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex
Sarbassov, D. D., Guertin, D. A., Ali, S. M., & Sabatini, D. M. (2005) · Science · doi:10.1126/science.1106148 · Cited by 6,216 · see citing works
Jaakkola, P., Mole, D. R., Tian, Y.-M., Wilson, M. I., Gielbert, J., Gaskell, S. J., Kriegsheim, A. V., Hebestreit, H. F., Mukherji, M., Schofield, C. J., et al. (2001) · Science · doi:10.1126/science.1059796 · Cited by 5,535 · see citing works
Ivan, M., Kondo, K., Yang, H., Kim, W., Valiando, J., Ohh, M., Salic, A., Asara, J. M., Lane, W. S., & Kaelin Jr., W. G. (2001) · Science · doi:10.1126/science.1059817 · Cited by 4,735 · cited 1× · see citing works
“The von Hippel–Lindau (VHL) tumour suppressor protein is frequently lost in renal cell carcinoma (RCC) and results in a state of ‘pseudohypoxia’ by activating HIF signallin”
BackgroundKim, J.-W., Tchernyshyov, I., Semenza, G. L., & Dang, C. V. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.02.002 · Cited by 3,905 · see citing works
T cell receptor antagonist peptides induce positive selection.
Hogquist, K., Jameson, S., Heath, W., Howard, J. L., Bevan, M., & Carbone, F. (1994) · Cell · doi:10.1016/0092-8674(94)90169-4 · Cited by 3,252 · see citing works
DeBerardinis, R. J., Mancuso, A., Daikhin, E., Nissim, I., Yudkoff, M., Wehrli, S., & Thompson, C. B. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0709747104 · Cited by 2,622 · see citing works
ATP-citrate lyase links cellular metabolism to histone acetylation
Wellen, K. E., Hatzivassiliou, G., Sachdeva, U. M., Bui, T. V., Cross, J. R., & Thompson, C. B. (2009) · Science · doi:10.1126/science.1164097 · Cited by 2,298 · see citing works
HIF-1 mediates adaptation to hypoxia by actively downregulating mitochondrial oxygen consumption
Papandreou, I., Cairns, R. A., Fontana, L., Lim, A. L., & Denko, N. C. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.01.012 · Cited by 2,267 · see citing works
Gao, P., Tchernyshyov, I., Chang, T.-C., Lee, Y.-S., Kita, K., Ochi, T., Zeller, K. I., De Marzo, A. M., Van Eyk, J. E., Mendell, J. T., et al. (2009) · Nature · doi:10.1038/nature07823 · Cited by 2,124 · see citing works
Ward, P. S., Patel, J., Wise, D. R., Abdel-Wahab, O., Bennett, B. D., Coller, H. A., Cross, J. R., Fantin, V. R., Hedvat, C. V., Perl, A. E., et al. (2010) · Cancer Cell · doi:10.1016/j.ccr.2010.01.020 · Cited by 2,020 · see citing works
Cell and environment interactions in tumor microregions: the multicell spheroid model.
Sutherland, R. M. (1988) · Science · doi:10.1126/science.2451290 · Cited by 1,803 · see citing works
Mitochondrial metabolism and ROS generation are essential for Kras-mediated tumorigenicity
Weinberg, F., Hamanaka, R., Wheaton, W. W., Weinberg, S., Joseph, J., Lopez, M., Kalyanaraman, B., Mutlu, G. M., Budinger, G. R. S., & Chandel, N. S. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1003428107 · Cited by 1,742 · see citing works
Bonnet, S., Archer, S. L., Allalunis‐Turner, J., Haromy, A., Beaulieu, C., Thompson, R. B., Lee, C. T., Lopaschuk, G. D., Puttagunta, L., Bonnet, S. B., et al. (2007) · Cancer Cell · doi:10.1016/j.ccr.2006.10.020 · Cited by 1,530 · see citing works
HIF-1: upstream and downstream of cancer metabolism
Semenza, G. L. (2009) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2009.10.009 · Cited by 1,381 · see citing works
ATP citrate lyase inhibition can suppress tumor cell growth
Hatzivassiliou, G., Zhao, F., Bauer, D. E., Andreadis, C., Shaw, A. N., Dhanak, D., Hingorani, S. R., Tuveson, D. A., & Thompson, C. B. (2005) · Cancer Cell · doi:10.1016/j.ccr.2005.09.008 · Cited by 1,086 · see citing works
Molecular basis of the VHL hereditary cancer syndrome
Kaelin, W. G. (2002) · Nature Reviews Cancer · doi:10.1038/nrc885 · Cited by 865 · see citing works
HIF-2α Promotes Hypoxic Cell Proliferation by Enhancing c-Myc Transcriptional Activity
Gordan, J. D., Bertout, J. A., Hu, C.-J., Diehl, J. A., & Simon, M. C. (2007) · Cancer Cell · doi:10.1016/j.ccr.2007.02.006 · Cited by 781 · see citing works
Tumour suppression by the human von Hippel-Lindau gene product
Iliopoulos, O., Kibel, A. S., Gray, S. G., & Kaelin, W. G. (1995) · Nature Medicine · doi:10.1038/nm0895-822 · Cited by 696 · see citing works
Self-citationMetabolic networks in motion: 13C‐based flux analysis
Sauer, U. (2006) · Molecular Systems Biology · doi:10.1038/msb4100109 · Cited by 664 · see citing works
Munger, J. C., Bennett, B. D., Parikh, A., Feng, X., McArdle, J., RABITZ, H. A., Shenk, T. E., & Rabinowitz, J. D. (2008) · Nature Biotechnology · doi:10.1038/nbt.1500 · Cited by 630 · see citing works
Elementary metabolite units (EMU): A novel framework for modeling isotopic distributions
Antoniewicz, M. R., Kelleher, J. K., & Stephanopoulos, G. N. (2006) · Metabolic Engineering · doi:10.1016/j.ymben.2006.09.001 · Cited by 544 · see citing works
Self-citationOncogenic K‐Ras decouples glucose and glutamine metabolism to support cancer cell growth
Gaglio, D., Metallo, C. M., Gameiro, P. A., Hiller, K., Danna, L. S., Balestrieri, C., Alberghina, L., Stephanopoulos, G., & Chiaradonna, F. (2011) · Molecular Systems Biology · doi:10.1038/msb.2011.56 · Cited by 492 · see citing works
Self-citationPyruvate carboxylase is required for glutamine-independent growth of tumor cells
Cheng, T., Sudderth, J., Yang, C., Mullen, A. R., Jin, E. S., Matés, J. M., & DeBerardinis, R. J. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1016627108 · Cited by 475 · see citing works
Determination of confidence intervals of metabolic fluxes estimated from stable isotope measurements
Antoniewicz, M. R., Kelleher, J. K., & Stephanopoulos, G. N. (2006) · Metabolic Engineering · doi:10.1016/j.ymben.2006.01.004 · Cited by 451 · see citing works
Self-citationATP citrate lyase: activation and therapeutic implications in non-small cell lung cancer
Migita, T., Narita, T., Nomura, K., Miyagi, E., Inazuka, F., Matsuura, M., Ushijima, M., Mashima, T., Seimiya, H., Satoh, Y., et al. (2008) · Cancer Research · doi:10.1158/0008-5472.can-08-1235 · Cited by 403 · see citing works
Quiescent Fibroblasts Exhibit High Metabolic Activity
Lemons, J. M. S., Feng, X., Bennett, B. D., Legesse-Miller, A., Johnson, E. L., Raitman, I., Pollina, E. A., RABITZ, H. A., Rabinowitz, J. D., & Coller, H. A. (2010) · PLoS Biology · doi:10.1371/journal.pbio.1000514 · Cited by 377 · see citing works
Quantifying Reductive Carboxylation Flux of Glutamine to Lipid in a Brown Adipocyte Cell Line
Yoo, H., Antoniewicz, M. R., Stephanopoulos, G., & Kelleher, J. K. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m706494200 · Cited by 301 · see citing works
Self-citationHigh Precision Isotope Ratio Monitoring Techniques in Mass Spectrometry
Brand, W. A. (1996) · Journal of Mass Spectrometry · doi:10.1002/(sici)1096-9888(199603)31:3 · Cited by 299 · see citing works
Evaluation of 13C isotopic tracers for metabolic flux analysis in mammalian cells
Metallo, C. M., Walther, J. L., & Stephanopoulos, G. (2009) · Journal of Biotechnology · doi:10.1016/j.jbiotec.2009.07.010 · Cited by 280 · see citing works
Self-citationAn elementary metabolite unit (EMU) based method of isotopically nonstationary flux analysis
Young, J. D., Walther, J. L., Antoniewicz, M. R., Yoo, H., & Stephanopoulos, G. N. (2007) · Biotechnology and Bioengineering · doi:10.1002/bit.21632 · Cited by 257 · see citing works
Self-citationInhibition of hypoxia-inducible factor is sufficient for growth suppression of VHL−/− tumors
Zimmer, M., Doucette, D., Siddiqui, N., & Iliopoulos, O. (2004) · Molecular Cancer Research · doi:10.1158/1541-7786.89.2.2 · Cited by 244 · see citing works
Self-citationSazanov, L. A., & Jackson, J. B. (1994) · FEBS Letters · doi:10.1016/0014-5793(94)00370-x · Cited by 205 · see citing works
Zimmer, M., Ebert, B. L., Neil, C., Brenner, K., Papaioannou, I., Melas, A., Tolliday, N., Lamb, J., Pantopoulos, K., Golub, T., et al. (2008) · Molecular Cell · doi:10.1016/j.molcel.2008.12.004 · Cited by 191 · see citing works
Self-citationErk regulation of pyruvate dehydrogenase flux through PDK4 modulates cell proliferationPreprint
Grassian, A. R., Metallo, C. M., Coloff, J. L., Stephanopoulos, G. N., & Brugge, J. S. (2011) · Genes & Development · doi:10.1101/gad.16771811 · Cited by 178 · see citing works
Self-citationInsights from retinitis pigmentosa into the roles of isocitrate dehydrogenases in the Krebs cycle
Hartong, D. T., Dange, M., McGee, T. L., Berson, E. L., Dryja, T. P., & Colman, R. F. (2008) · Nature Genetics · doi:10.1038/ng.223 · Cited by 172 · see citing works
Isotopomer Analysis of Citric Acid Cycle and Gluconeogenesis in Rat Liver
Rosiers, C. D., Donato, L. D., Comte, B., Laplante, A., Marcoux, C., David, F., Fernandez, C. A., & Brunengraber, H. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.17.10027 · Cited by 114 · see citing works
THE ENZYMATIC PROPERTIES OF ISOCITRIC DEHYDROGENASE
Siebert, G., Carsiotis, M., & Plaut, G. W. E. (1957) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)70883-1 · Cited by 104 · see citing works
Maier, K., Hofmann, U., Reuß, M., & Mauch, K. (2007) · Biotechnology and Bioengineering · doi:10.1002/bit.21746 · Cited by 96 · see citing works
Evidence for an InsP3-gated channel protein in isolated rat olfactory cilia
Restrepo, D., Teeter, J. H., Honda, E., Boyle, A. G., Marecek, J. F., Prestwich, G. D., & Kalinoski, D. L. (1992) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1992.263.3.c667 · Cited by 76 · see citing works
Boros, L. G., Steinkamp, M. P., Fleming, J. C., Lee, W. P., Cascante, M., & Neufeld, E. J. (2003) · Blood · doi:10.1182/blood-2003-05-1537 · Cited by 75 · see citing works
Effect of Anaplerotic Fluxes and Amino Acid Availability on Hepatic Lipoapoptosis
Noguchi, Y., Young, J. D., Alemán, J. O., Hansen, M. A. E., Kelleher, J. K., & Stephanopoulos, G. N. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.049478 · Cited by 71 · see citing works
Self-citationIsotopomer spectral analysis of triglyceride fatty acid synthesis in 3T3-L1 cells
Kharroubi, A., Masterson, T. M., Aldaghlas, T., Kennedy, K. A., & Kelleher, J. K. (1992) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1992.263.4.e667 · Cited by 62 · see citing works
Self-citation
Flagged first, then by citations
1 of the 43 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
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 · see citing works
Comprehensive molecular characterization of clear cell renal cell carcinoma
The Cancer Genome Atlas Research Network (2013) · Nature · doi:10.1038/nature12222 · Cited by 3,485 · see citing works
Metabolic Reprogramming: A Cancer Hallmark Even Warburg Did Not Anticipate
Ward, P. S., & Thompson, C. B. (2012) · Cancer Cell · doi:10.1016/j.ccr.2012.02.014 · Cited by 3,233 · see citing works
Aerobic glycolysis: Meeting the metabolic requirements of cell proliferation
Lunt, S. Y., & Vander Heiden, M. G. (2011) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-092910-154237 · Cited by 3,057 · see citing works
Fundamentals of Cancer Metabolism
DeBerardinis, R. J., & Chandel, N. S. (2016) · Science Advances · doi:10.1126/sciadv.1600200 · Cited by 3,013 · see citing works
Posttranscriptional Control of T Cell Effector Function by Aerobic Glycolysis
Chang, C.-H., Curtis, J. D., Maggi, L. B., Faubert, B., Villarino, A. V., O’Sullivan, D., Huang, S. C.-C., van der Windt, G. J. W., Blagih, J., Qiu, J., et al. (2013) · Cell · doi:10.1016/j.cell.2013.05.016 · Cited by 2,204 · see citing works
From Krebs to clinic: glutamine metabolism to cancer therapy
Altman, B. J., Stine, Z. E., & Dang, C. V. (2016) · Nature Reviews Cancer · doi:10.1038/nrc.2016.71 · Cited by 2,119 · see citing works
Cellular Fatty Acid Metabolism and Cancer
Currie, E., Schulze, A., Zechner, R., Walther, T. C., & Farese, R. V. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.05.017 · Cited by 2,123 · see citing works
Kleeff, J., Korc, M., Apte, M., La Vecchia, C., Johnson, C. D., Biankin, A. V., Neale, R. E., Tempero, M., Tuveson, D. A., Hruban, R. H., et al. (2016) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2016.22 · Cited by 1,982 · see citing works
The multifaceted contributions of mitochondria to cellular metabolism
Spinelli, J. B., & Haigis, M. C. (2018) · Nature Cell Biology · doi:10.1038/s41556-018-0124-1 · Cited by 1,935 · see citing works
Macropinocytosis of protein is an amino acid supply route in Ras-transformed cells
Commisso, C., Davidson, S. M., Soydaner-Azeloglu, R. G., Parker, S. J., Kamphorst, J. J., Hackett, S., Grabocka, E., Nofal, M., Drebin, J. A., Thompson, C. B., et al. (2013) · Nature · doi:10.1038/nature12138 · Cited by 1,683 · see citing works
Self-citationThe multifaceted roles of fatty acid synthesis in cancer
Röhrig, F., & Schulze, A. (2016) · Nature Reviews Cancer · doi:10.1038/nrc.2016.89 · Cited by 1,651 · see citing works
Reprogramming of fatty acid metabolism in cancer
Koundouros, N., & Poulogiannis, G. (2019) · British Journal of Cancer · doi:10.1038/s41416-019-0650-z · Cited by 1,621 · see citing works
Cancer metabolism: a therapeutic perspective
Martinez-Outschoorn, U. E., Peiris-Pagés, M., Pestell, R. G., Sotgia, F., & Lisanti, M. P. (2017) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2016.60 · Cited by 1,505 · see citing works
The hallmarks of cancer metabolism: still emerging
Pavlova, N. N., Zhu, J., & Thompson, C. B. (2022) · Cell Metabolism · doi:10.1016/j.cmet.2022.01.007 · Cited by 1,418 · see citing works
Birsoy, K., Wang, T., Chen, W. W., Freinkman, E., Abu-Remaileh, M., & Sabatini, D. M. (2015) · Cell · doi:10.1016/j.cell.2015.07.016 · Cited by 1,388 · see citing works
Targeting mitochondria metabolism for cancer therapy
Weinberg, S. E., & Chandel, N. S. (2014) · Nature Chemical Biology · doi:10.1038/nchembio.1712 · Cited by 1,385 · see citing works
Acetyl Coenzyme A: A Central Metabolite and Second Messenger
Pietrocola, F., Galluzzi, L., Pedro, J. M. B., Madeo, F., & Kroemer, G. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.05.014 · Cited by 1,349 · see citing works
Fueling Immunity: Insights into Metabolism and Lymphocyte Function
Pearce, E. L., Poffenberger, M. C., Chang, C.-H., & Jones, R. G. (2013) · Science · doi:10.1126/science.1242454 · Cited by 1,363 · see citing works
Santos, C. R., & Schulze, A. (2012) · FEBS Journal · doi:10.1111/j.1742-4658.2012.08644.x · Cited by 1,344 · see citing works
HIF-1 mediates metabolic responses to intratumoral hypoxia and oncogenic mutations
Semenza, G. L. (2013) · Journal of Clinical Investigation · doi:10.1172/jci67230 · Cited by 1,335 · see citing works
Mitochondrial metabolism and cancer
Porporato, P. E., Filigheddu, N., Pedro, J. M. B., Kroemer, G., & Galluzzi, L. (2017) · Cell Research · doi:10.1038/cr.2017.155 · Cited by 1,292 · see citing works
Glutamine and cancer: cell biology, physiology, and clinical opportunities
Hensley, C. T., Wasti, A. T., & DeBerardinis, R. J. (2013) · Journal of Clinical Investigation · doi:10.1172/jci69600 · Cited by 1,262 · see citing works
Oxygen Sensing, Hypoxia-Inducible Factors, and Disease Pathophysiology
Semenza, G. L. (2013) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathol-012513-104720 · Cited by 1,159 · see citing works
ROS homeostasis and metabolism: a dangerous liason in cancer cells
Panieri, E., & Santoro, M. M. (2016) · Cell Death and Disease · doi:10.1038/cddis.2016.105 · Cited by 1,156 · see citing works
Pancreatic stellate cells support tumour metabolism through autophagic alanine secretion
Sousa, C. M., Biancur, D. E., Wang, X., Halbrook, C. J., Sherman, M. H., Zhang, L., Kremer, D., Hwang, R. F., Witkiewicz, A. K., Ying, H., et al. (2016) · Nature · doi:10.1038/nature19084 · Cited by 1,122 · see citing works
Glucose-Independent Glutamine Metabolism via TCA Cycling for Proliferation and Survival in B Cells
Le, A., Lane, A. N., Hamaker, M., Bose, S., Gouw, A., Barbi, J., Tsukamoto, T., Rojas, C. J., Slusher, B. S., Zhang, H., et al. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2011.12.009 · Cited by 1,095 · see citing works
Glutamine reliance in cell metabolism
Yoo, H. C., Yu, Y. C., Sung, Y., & Han, J. M. (2020) · Experimental & Molecular Medicine · doi:10.1038/s12276-020-00504-8 · Cited by 1,021 · see citing works
Links between metabolism and cancerPreprint
Dang, C. V. (2012) · Genes & Development · doi:10.1101/gad.189365.112 · Cited by 991 · see citing works
Tumour acidosis: from the passenger to the driver's seat
Corbet, C., & Féron, O. (2017) · Nature reviews. Cancer · doi:10.1038/nrc.2017.77 · Cited by 998 · see citing works
Bian, X., Liu, R. R., Meng, Y., Xing, D., Xu, D., & Lu, Z. (2020) · The Journal of Experimental Medicine · doi:10.1084/jem.20201606 · Cited by 1,007 · see citing works
Hypoxia-Inducible Factors: Master Regulators of Cancer Progression
Schito, L., & Semenza, G. L. (2016) · Trends in Cancer · doi:10.1016/j.trecan.2016.10.016 · Cited by 962 · see citing works
Cancer Cell Metabolism: One Hallmark, Many Faces
Cantor, J. R., & Sabatini, D. M. (2012) · Cancer Discovery · doi:10.1158/2159-8290.cd-12-0345 · Cited by 945 · see citing works
How cancer metabolism is tuned for proliferation and vulnerable to disruption
Schulze, A., & Harris, A. L. (2012) · Nature · doi:10.1038/nature11706 · Cited by 927 · see citing works
Tumor microenvironment derived exosomes pleiotropically modulate cancer cell metabolism
Zhao, H., Yang, L., Baddour, J., Achreja, A., Bernard, V., Moss, T., Marini, J. C., Tudawe, T., Seviour, E. G., San Lucas, F. A., et al. (2016) · eLife · doi:10.7554/elife.10250 · Cited by 927 · see citing works
Glutaminolysis: A Hallmark of Cancer Metabolism
Yang, L., Venneti, S., & Nagrath, D. (2017) · Annual Review of Biomedical Engineering · doi:10.1146/annurev-bioeng-071516-044546 · Cited by 859 · see citing works
Cellular Metabolism and Disease: What Do Metabolic Outliers Teach Us?
DeBerardinis, R. J., & Thompson, C. B. (2012) · Cell · doi:10.1016/j.cell.2012.02.032 · Cited by 858 · see citing works
Lipid metabolism reprogramming and its potential targets in cancer
Cheng, C., Geng, F., Cheng, X., & Guo, D. (2018) · 癌症：英文版 · doi:10.1186/s40880-018-0301-4 · Cited by 862 · see citing works
Metabolomics and Isotope Tracing
Jang, C., Chen, L., & Rabinowitz, J. D. (2018) · Cell · doi:10.1016/j.cell.2018.03.055 · Cited by 841 · see citing works
Reprogramming of glucose, fatty acid and amino acid metabolism for cancer progression
Li, Z., & Zhang, H. (2015) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-015-2070-4 · Cited by 829 · see citing works
Lieu, E. L., Nguyen, T. A., Rhyne, S., & Kim, J. (2020) · Experimental & Molecular Medicine · doi:10.1038/s12276-020-0375-3 · Cited by 827 · see citing works
Schug, Z. T., Peck, B., Jones, D. T., Zhang, Q., Grosskurth, S., Alam, I. S., Goodwin, L. M., Smethurst, E., Mason, S., Blyth, K., et al. (2015) · Cancer Cell · doi:10.1016/j.ccell.2014.12.002 · Cited by 820 · see citing works
Transcriptional control of autophagy-lysosome function drives pancreatic cancer metabolism
Perera, R. M., Stoykova, S., Nicolay, B. N., Ross, K. N., Fitamant, J., Boukhali, M., Lengrand, J., Deshpande, V., Selig, M. K., Ferrone, C. R., et al. (2015) · Nature · doi:10.1038/nature14587 · Cited by 799 · see citing works
Self-citationPyruvate kinase M2 activators promote tetramer formation and suppress tumorigenesis
Anastasiou, D., Yu, Y., Israelsen, W. J., Jiang, J.-K., Boxer, M. B., Hong, B. S., Tempel, W., Dimov, S., Shen, M., Jha, A., et al. (2012) · Nature Chemical Biology · doi:10.1038/nchembio.1060 · Cited by 816 · see citing works
Self-citationTargeting oncogenic Myc as a strategy for cancer treatment
Chen, H., Liu, H., & Qing, G. (2018) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-018-0008-7 · Cited by 806 · see citing works
An Integrated Metabolic Atlas of Clear Cell Renal Cell Carcinoma
Hakimi, A. A., Reznik, E., Lee, C., Creighton, C. J., Brannon, A. R., Luna, A., Aksoy, B. A., Liu, E. M., Shen, R., Lee, W., et al. (2016) · Cancer Cell · doi:10.1016/j.ccell.2015.12.004 · Cited by 791 · see citing works
Metabolic reprogramming and epigenetic modifications on the path to cancer
Sun, L., Zhang, H., & Gao, P. (2021) · Protein & Cell · doi:10.1007/s13238-021-00846-7 · Cited by 796 · see citing works
Hooked on fat: the role of lipid synthesis in cancer metabolism and tumour development
Baenke, F., Peck, B., Miess, H., & Schulze, A. (2013) · Disease Models & Mechanisms · doi:10.1242/dmm.011338 · Cited by 772 · see citing works
Mitochondrial Metabolism as a Target for Cancer Therapy
Vasan, K., Werner, M., & Chandel, N. S. (2020) · Cell Metabolism · doi:10.1016/j.cmet.2020.06.019 · Cited by 746 · see citing works
Hypoxia and Metabolic Adaptation of Cancer Cells
Eales, K. L., Hollinshead, K. E. R., & Tennant, D. A. (2016) · Oncogenesis · doi:10.1038/oncsis.2015.50 · Cited by 724 · see citing works
Kamphorst, J. J., Cross, J. R., Fan, J., de Stanchina, E., Mathew, R., White, E. P., Thompson, C. B., & Rabinowitz, J. D. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1307237110 · Cited by 726 · see citing works
Metabolic targets for cancer therapy
Galluzzi, L., Kepp, O., Heiden, M. G. V., & Kroemer, G. (2013) · Nature Reviews Drug Discovery · doi:10.1038/nrd4145 · Cited by 705 · see citing works
Comerford, S. A., Huang, Z., Du, X., Wang, Y., Cai, L., Witkiewicz, A. K., Walters, H., Tantawy, M. N., Fu, A., Manning, H. C., et al. (2014) · Cell · doi:10.1016/j.cell.2014.11.020 · Cited by 681 · see citing works
Metabolic Regulation of Epigenetics
Lu, C., & Thompson, C. B. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.06.001 · Cited by 699 · see citing works
Yang, C., Ko, B., Hensley, C. T., Jiang, L., Wasti, A. T., Kim, J., Sudderth, J., Calvaruso, M. A., Lumata, L., Mitsche, M., et al. (2014) · Molecular Cell · doi:10.1016/j.molcel.2014.09.025 · Cited by 679 · see citing works
Metabolic programming and immune suppression in the tumor microenvironment
Arner, E. N., & Rathmell, J. C. (2023) · Cancer Cell · doi:10.1016/j.ccell.2023.01.009 · Cited by 692 · see citing works
Hosios, A. M., Hecht, V. C., Danai, L. V., Johnson, M. O., Rathmell, J. C., Steinhauser, M. L., Manalis, S. R., & Vander Heiden, M. G. (2016) · Developmental Cell · doi:10.1016/j.devcel.2016.02.012 · Cited by 641 · see citing works
Mitochondria and Mitochondrial ROS in Cancer: Novel Targets for Anticancer Therapy
Yang, Y., Karakhanova, S., Hartwig, W., D’Haese, J. G., Philippov, P. P., Werner, J., & Bazhin, A. V. (2016) · Journal of Cellular Physiology · doi:10.1002/jcp.25349 · Cited by 671 · see citing works
Bensaad, K., Favaro, E., Lewis, C. A., Peck, B., Lord, S., Collins, J. M., Pinnick, K. E., Wigfield, S., Buffa, F. M., Li, J., et al. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.08.056 · Cited by 667 · see citing works
Keap1 loss promotes Kras-driven lung cancer and results in dependence on glutaminolysis
Romero, R., Sayin, V. I., Davidson, S. M., Bauer, M. R., Singh, S. X., LeBoeuf, S. E., Karakousi, T. R., Ellis, D. C., Bhutkar, A., Sánchez-Rivera, F. J., et al. (2017) · Nature Medicine · doi:10.1038/nm.4407 · Cited by 652 · see citing works
How the Warburg effect supports aggressiveness and drug resistance of cancer cells?
Icard, P., Shulman, S. D., Farhat, D., Steyaert, J., Alifano, M., & Lincet, H. (2018) · Drug Resistance Updates · doi:10.1016/j.drup.2018.03.001 · Cited by 648 · see citing works
Mitochondrial composition and function under the control of hypoxia
Fuhrmann, D. C., & Brüne, B. (2017) · Redox Biology · doi:10.1016/j.redox.2017.02.012 · Cited by 646 · see citing works
A roadmap for interpreting 13C metabolite labeling patterns from cells
Buescher, J. M., Antoniewicz, M. R., Boros, L. G., Burgess, S. C., Brunengraber, H., Clish, C. B., DeBerardinis, R. J., Féron, O., Frezza, C., Ghesquière, B., et al. (2015) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2015.02.003 · Cited by 623 · see citing works
Self-citationMechanisms controlling pancreatic islet cell function in insulin secretion
Campbell, J. E., & Newgard, C. B. (2021) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-00317-7 · Cited by 631 · see citing works
Endothelial Cell Metabolism in Normal and Diseased Vasculature
Eelen, G., de Zeeuw, P., Simons, M., & Carmeliet, P. (2015) · Circulation Research · doi:10.1161/circresaha.116.302855 · Cited by 619 · see citing works
Tracing compartmentalized NADPH metabolism in the cytosol and mitochondria of mammalian cells
Lewis, C. A., Parker, S. J., Fiske, B. P., McCloskey, D., Gui, D. Y., Green, C. R., Vokes, N. I., Feist, A. M., Vander Heiden, M. G., & Metallo, C. M. (2014) · Molecular Cell · doi:10.1016/j.molcel.2014.05.008 · Cited by 562 · see citing works
Self-citationWhat a difference a hydroxyl makes: mutant IDH, (<i>R</i>)-2-hydroxyglutarate, and cancer
Losman, J.-A., & Kaelin, W. G. (2013) · Genes & Development · doi:10.1101/gad.217406.113 · Cited by 570 · see citing works
Reductive carboxylation supports redox homeostasis during anchorage-independent growth
Jiang, L., Shestov, A. A., Swain, P., Yang, C., Parker, S. J., Wang, Q. A., Terada, L. S., Adams, N. D., McCabe, M. T., Pietrak, B., et al. (2016) · Nature · doi:10.1038/nature17393 · Cited by 582 · see citing works
Self-citationLipid droplet functions beyond energy storage
Welte, M. A., & Gould, A. P. (2017) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2017.07.006 · Cited by 574 · see citing works
Metabolic reprogramming in clear cell renal cell carcinoma
Wettersten, H. I., Aboud, O. A., Lara, P. N., & Weiss, R. H. (2017) · Nature Reviews Nephrology · doi:10.1038/nrneph.2017.59 · Cited by 573 · see citing works
Emerging insights into the molecular and cellular basis of glioblastomaPreprint
Dunn, G. P., Rinne, M. L., Wykosky, J., Genovese, G., Quayle, S. N., Dunn, I. F., Agarwalla, P. K., Chheda, M. G., Campos, B., Wang, A., et al. (2012) · Genes & Development · doi:10.1101/gad.187922.112 · Cited by 559 · see citing works
Metabolic switching and fuel choice during T‐cell differentiation and memory development
van der Windt, G. J. W., & Pearce, E. L. (2012) · Immunological Reviews · doi:10.1111/j.1600-065x.2012.01150.x · Cited by 563 · see citing works
PDK1-Dependent Metabolic Reprogramming Dictates Metastatic Potential in Breast Cancer
Dupuy, F., Tabariès, S., Andrzejewski, S., Dong, Z., Blagih, J., Annis, M. G., Omeroglu, A., Gao, D., Leung, S., Amir, E., et al. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.08.007 · Cited by 558 · see citing works
Tardito, S., Oudin, A., Ahmed, S. U., Fack, F., Keunen, O., Zheng, L., Miletic, H., Sakariassen, P. Ø., Weinstock, A., Wagner, A., et al. (2015) · Nature Cell Biology · doi:10.1038/ncb3272 · Cited by 557 · see citing works
The emerging role and targetability of the TCA cycle in cancer metabolism
Anderson, N. M., Mucka, P., Kern, J. G., & Feng, H. (2017) · Protein & Cell · doi:10.1007/s13238-017-0451-1 · Cited by 558 · see citing works
Cancer Metabolism: Phenotype, Signaling and Therapeutic Targets
Park, J. H., Pyun, W. Y., & Park, H. W. (2020) · Cells · doi:10.3390/cells9102308 · Cited by 558 · see citing works
ATP-Citrate Lyase: A Key Player in Cancer Metabolism
Zaidi, N., Swinnen, J. V., & Smans, K. A. (2012) · Cancer Research · doi:10.1158/0008-5472.can-11-4112 · Cited by 549 · see citing works
Svensson, R. U., Parker, S. J., Eichner, L. J., Kolar, M. J., Wallace, M., Brun, S. N., Lombardo, P. S., Van Nostrand, J. L., Hutchins, A., Vera, L., et al. (2016) · Nature Medicine · doi:10.1038/nm.4181 · Cited by 536 · see citing works
Self-citationFructose-1,6-bisphosphatase opposes renal carcinoma progression
Li, B., Qiu, B., Lee, D. S. M., Walton, Z. E., Ochocki, J. D., Mathew, L. K., Mancuso, A., Gade, T. P. F., Keith, B., Nissim, I., et al. (2014) · Nature · doi:10.1038/nature13557 · Cited by 535 · see citing works
Hypoxia Induces Production of L-2-Hydroxyglutarate
Intlekofer, A. M., Dematteo, R. G., Venneti, S., Finley, L. W. S., Lu, C., Judkins, A. R., Rustenburg, A. S., Grinaway, P. B., Chodera, J. D., Cross, J. R., et al. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.06.023 · Cited by 513 · see citing works
A two-way street: reciprocal regulation of metabolism and signalling
Wellen, K. E., & Thompson, C. B. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3305 · Cited by 528 · see citing works
Regulation and function of the mammalian tricarboxylic acid cycle
Arnold, P. K., & Finley, L. W. S. (2023) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2022.102838 · Cited by 535 · see citing works
“During reductive carboxylation, glutamine-derived αKG is converted to isocitrate and then to citrate through reverse isocitrate dehydrogenase (IDH) and aconitase (ACO) activity, respectively (122, 123).”
BackgroundCordes, T., Wallace, M., Michelucci, A., Divakaruni, A. S., Sapcariu, S. C., Sousa, C., Koseki, H., Cabrales, P., Murphy, A. N., Hiller, K., et al. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.685792 · Cited by 526 · see citing works
Self-citationAnalysis and Interpretation of Microplate-Based Oxygen Consumption and pH Data
Divakaruni, A. S., Paradyse, A. R., Ferrick, D. A., Murphy, A. N., & Jastroch, M. (2014) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/b978-0-12-801415-8.00016-3 · Cited by 525 · see citing works
The effect of HIF on metabolism and immunity
Taylor, C. T., & Scholz, C. C. (2022) · Nature Reviews Nephrology · doi:10.1038/s41581-022-00587-8 · Cited by 517 · see citing works
IDH mutations in cancer and progress toward development of targeted therapeutics
Dang, L., Yen, K., & Attar, E. C. (2016) · Annals of Oncology · doi:10.1093/annonc/mdw013 · Cited by 509 · see citing works
Mitochondrial Dysfunction in Cancer
Boland, M. L., Chourasia, A. H., & Macleod, K. F. (2013) · Frontiers in Oncology · doi:10.3389/fonc.2013.00292 · Cited by 502 · see citing works
Pyruvate carboxylase is critical for non–small-cell lung cancer proliferation
Sellers, K., Fox, M. P., Bousamra, M., Slone, S. P., Higashi, R. M., Miller, D. M., Wang, Y., Yan, J., Yuneva, M. O., Deshpande, R., et al. (2015) · Journal of Clinical Investigation · doi:10.1172/jci72873 · Cited by 497 · see citing works
Therapeutic targeting of the hypoxic tumour microenvironment
Singleton, D. C., Macann, A., & Wilson, W. R. (2021) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-021-00539-4 · Cited by 493 · see citing works
BCAT1 promotes cell proliferation through amino acid catabolism in gliomas carrying wild-type IDH1
Tönjes, M., Barbus, S., Park, Y. J., Wang, W., Schlotter, M., Lindroth, A. M., Pleier, S. V., Bai, A. H. C., Karra, D., Piro, R. M., et al. (2013) · Nature Medicine · doi:10.1038/nm.3217 · Cited by 486 · see citing works
Lipid metabolic reprogramming in tumor microenvironment: from mechanisms to therapeutics
Jin, H.-R., Wang, J., Wang, Z., Xi, M., Xia, B., Deng, K., & Yang, J. (2023) · Journal of Hematology & Oncology · doi:10.1186/s13045-023-01498-2 · Cited by 509 · see citing works
Self-citationLiu, W., Le, A., Hancock, C., Lane, A. N., Dang, C. V., Fan, T. W.-M., & Phang, J. M. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1203244109 · Cited by 483 · see citing works
Acetate functions as an epigenetic metabolite to promote lipid synthesis under hypoxia
Gao, X. J., Lin, S., Ren, F., Li, J.-T., Chen, J.-J., Yao, C.-B., Yang, H., Jiang, S.-X., Yan, G.-Q., Wang, D., et al. (2016) · Nature Communications · doi:10.1038/ncomms11960 · Cited by 481 · see citing works
Branched-chain amino acid catabolism fuels adipocyte differentiation and lipogenesis
Green, C. R., Wallace, M., Divakaruni, A. S., Phillips, S. A., Murphy, A. N., Ciaraldi, T. P., & Metallo, C. M. (2016) · Nature Chemical Biology · doi:10.1038/nchembio.1961 · Cited by 471 · see citing works
Self-citationHIF drives lipid deposition and cancer in ccRCC via repression of fatty acid metabolism
Du, W., Zhang, L., Brett-Morris, A., Aguila, B., Kerner, J., Hoppel, C. L., Puchowicz, M., Serra, D., Herrero, L., Rini, B. I., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-01965-8 · Cited by 468 · see citing works
IDH1andIDH2Mutations in Tumorigenesis: Mechanistic Insights and Clinical Perspectives
Yang, H., Ye, D., Guan, K., & Xiong, Y. (2012) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-12-1773 · Cited by 459 · see citing works
Glutaminolysis as a target for cancer therapy
Jin, L., Alesi, G. N., & Kang, S. (2016) · Oncogene · doi:10.1038/onc.2015.447 · Cited by 459 · see citing works
Extreme vulnerability of IDH1 mutant cancers to NAD+ depletion
Tateishi, K., Wakimoto, H., Iafrate, A. J., Tanaka, S., Loebel, F., Lelic, N., Wiederschain, D., Bedel, O., Deng, G., Zhang, B., et al. (2015) · Cancer Cell · doi:10.1016/j.ccell.2015.11.006 · Cited by 433 · see citing works
Oncogenic Isocitrate Dehydrogenase Mutations: Mechanisms, Models, and Clinical Opportunities
Cairns, R. A., & Mak, T. W. (2013) · Cancer Discovery · doi:10.1158/2159-8290.cd-13-0083 · Cited by 452 · see citing works
Metabolism of stromal and immune cells in health and disease
Ghesquière, B., Wong, B. W., Kuchnio, A., & Carmeliet, P. (2014) · Nature · doi:10.1038/nature13312 · Cited by 451 · see citing works
- Authors
- Metallo, C. M., Gameiro, P. A., Bell, E. L., Mattaini, K. R., Yang, J., Hiller, K., Jewell, C. M., Johnson, Z. R., Irvine, D. J., Guarente, L., Kelleher, J. K., Vander Heiden, M. G., Iliopoulos, O., & Stephanopoulos, G.
- Affiliations
- Massachusetts Institute of Technology (US)
- Massachusetts General Hospital (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Iliopoulos, Othon
- Stephanopoulos, Gregory
- ORCID
- Venue
- Nature
- Published
- 2011-11-20
- Volume
- 481
- Issue
- 7381
- Pages
- 380-384
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3710581
- OpenAlex
- W2116516144
- Cited by
- 1,791
- References
- 43
- Citations by year
- 2026: 82 · 2025: 95 · 2024: 96 · 2023: 137 · 2022: 156 · 2021: 143 · 2020: 149 · 2019: 125 · 2018: 100 · 2017: 135 · 2016: 129 · 2015: 125 · 2014: 119 · 2013: 112 · 2012: 84
- FWCI
- 34.61
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc-sa)
- RePEc: Research Papers in Economics (submittedVersion)
- Open Repository and Bibliography (University of Luxembourg) (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- Damon Runyon Cancer Research Foundation
- Wellcome Trust
- Agios Pharmaceuticals
- National Institutes of Health
- National Cancer Institute (R01CA160458, R01CA122591, P30CA014051)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK075850)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Keywords
- IDH1, lipogenesis, hypoxia, reductive carboxylation, alpha-ketoglutarate, acetyl-CoA, fatty acid synthesis, VHL, renal cell carcinoma, cancer metabolism, mitochondrial dysfunction, aerobic glycolysis
- MeSH terms
- Endothelial PAS Domain-Containing Protein 1, Acetyl Coenzyme A, Carbon, Carcinoma, Renal Cell, Cells, Cultured, Citric Acid Cycle, Glutamine, Humans, Isocitrate Dehydrogenase, Ketoglutaric Acids, Kidney Neoplasms, Oxidation-Reduction, Oxygen, Cell Hypoxia, CD8-Positive T-Lymphocytes, Palmitic Acid, Cell Line, Tumor, Lipogenesis, Aryl Hydrocarbon Receptor Nuclear Translocator, Basic Helix-Loop-Helix Transcription Factors, Basic Helix-Loop-Helix Proteins, Von Hippel-Lindau Tumor Suppressor Protein, Hypoxia-Inducible Factor 1, alpha Subunit
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