Fumarate Hydratase Deficiency in Renal Cancer Induces Glycolytic Addiction and Hypoxia-Inducible Transcription Factor 1α Stabilization by Glucose-Dependent Generation of Reactive Oxygen Species
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Hereditary leiomyomatosis and renal cell cancer (HLRCC) is an inherited cancer syndrome linked to biallelic inactivation of the gene encoding the tricarboxylic acid cycle enzyme fumarate hydratase (FH). Individuals with HLRCC are at risk to develop cutaneous and uterine leiomyomas and an aggressive form of kidney cancer. Pseudohypoxic drive-the aberrant activation of cellular hypoxia response pathways despite normal oxygen tension-is considered to be a likely mechanism underlying the etiology of this tumor. Pseudohypoxia requires the oxygen-independent stabilization of the alpha subunit of the hypoxia-inducible transcription factor (HIF-1alpha). Under normoxic conditions, proline hydroxylation of HIF-1alpha permits VHL recognition and subsequent targeting for proteasomal degradation. Here, we demonstrate that inactivating mutations of FH in an HLRCC-derived cell line result in glucose-mediated generation of cellular reactive oxygen species (ROS) and ROS-dependent HIF-1alpha stabilization. Additionally, we demonstrate that stable knockdown of FH in immortalized renal epithelial cells results in ROS-dependent HIF-1alpha stabilization. These data reveal that the obligate glycolytic switch present in HLRCC is critical to HIF stabilization via ROS generation.
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Accumulation of reactive oxygen species, an independent trigger for HIF stabilization, may contribute to this process in some cases of defective SDH or FH.
“Accumulation of reactive oxygen species, an independent trigger for HIF stabilization, may contribute to this process in some cases of defective SDH or FH (Guzy et al., 2008; Sudarshan et al., 2009).”
From Cellular Metabolism and Disease: What Do Metabolic Outliers Teach Us? (2012) · cites this paper as Sudarshan et al., 2009
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Cites
Warburg, O. (1956) · Science · doi:10.1126/science.123.3191.309 · Cited by 13,425 · 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 · see citing works
Kim, 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
Epstein, A. C. R., Gleadle, J. M., McNeill, L. A., Hewitson, K. S., O'Rourke, J., Mole, D. R., Mukherji, M., Metzen, E., Wilson, M. I., Dhanda, A., et al. (2001) · Cell · doi:10.1016/s0092-8674(01)00507-4 · Cited by 3,333 · see citing works
A conserved family of prolyl-4-hydroxylases that modify HIF
Bruick, R. K., & McKnight, S. L. (2001) · Science · doi:10.1126/science.1066373 · Cited by 2,549 · see citing works
Succinate links TCA cycle dysfunction to oncogenesis by inhibiting HIF-α prolyl hydroxylase
Selak, M. A., Armour, S. M., MacKenzie, E. D., Boulahbel, H., Watson, D. G., Mansfield, K. D., Pan, Y., Simon, M. C., Thompson, C. B., & Gottlieb, E. (2005) · Cancer Cell · doi:10.1016/j.ccr.2004.11.022 · Cited by 2,108 · see citing works
Mutations of the VHL tumour suppressor gene in renal carcinoma
Gnarra, J. R., Tory, K., Weng, Y., Schmidt, L., Wei, M. H., Li, H., Latif, F., Liu, S., Chen, F., Duh, F.-M., et al. (1994) · Nature Genetics · doi:10.1038/ng0594-85 · Cited by 1,730 · see citing works
Self-citationHypoxia, HIF1 and glucose metabolism in the solid tumour
Denko, N. C. (2008) · Nature Reviews Cancer · doi:10.1038/nrc2468 · Cited by 1,707 · see citing works
The Multiple Leiomyoma Consortium (2002) · Nature Genetics · doi:10.1038/ng849 · Cited by 1,635 · see citing works
Fantin, V. R., St-Pierre, J., & Leder, P. (2006) · Cancer Cell · doi:10.1016/j.ccr.2006.04.023 · Cited by 1,635 · see citing works
Isaacs, J. S., Jung, Y. J., Mole, D. R., Lee, S., Torres-Cabala, C., Chung, Y.-L., Merino, M., Trepel, J., Zbar, B., Toro, J., et al. (2005) · Cancer Cell · doi:10.1016/j.ccr.2005.06.017 · Cited by 958 · see citing works
Self-citationPollard, P. J., Brière, J. J., Alam, N. A., Barwell, J., Barclay, E., Wortham, N. C., Hunt, T., Mitchell, M., Olpin, S., Moat, S. J., et al. (2005) · Human Molecular Genetics · doi:10.1093/hmg/ddi227 · Cited by 865 · see citing works
Walenta, S., Wetterling, M., Lehrke, M., Schwickert, G., Sundfør, K., Rofstad, E. K., & Mueller‐Klieser, W. (2000) · PubMed · Cited by 817 · see citing works
Inherited susceptibility to uterine leiomyomas and renal cell cancer
Launonen, V., Vierimaa, O., Kiuru, M., Isola, J., Roth, S., Pukkala, E., Sistonen, P., Herva, R., & Aaltonen, L. A. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.051633798 · Cited by 669 · see citing works
Mitochondrial tumour suppressors: a genetic and biochemical update
Gottlieb, E., & Tomlinson, I. P. M. (2005) · Nature reviews. Cancer · doi:10.1038/nrc1737 · Cited by 617 · see citing works
HIF-Dependent Antitumorigenic Effect of Antioxidants In Vivo
Gao, P., Zhang, H., Dinavahi, R., Li, F., Xiang, Y., Raman, V., Bhujwalla, Z. M., Felsher, D. W., Cheng, L., Pevsner, J., et al. (2007) · Cancer Cell · doi:10.1016/j.ccr.2007.08.004 · Cited by 523 · see citing works
Inhibition of Hypoxia-inducible Factor (HIF) Hydroxylases by Citric Acid Cycle Intermediates
Koivunen, P., Hirsilä, M., Remes, A. M., Hassinen, I. E., Kivirikko, K. I., & Myllyharju, J. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m610415200 · Cited by 521 · see citing works
Hypoxia-inducible factors: central regulators of the tumor phenotype
Gordan, J. D., & Simon, M. C. (2007) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2006.12.006 · Cited by 450 · see citing works
Inoguchi, T., Sonta, T., Tsubouchi, H., Etoh, T., Kakimoto, M., Sonoda, N., Sato, N., Sekiguchi, N., Kobayashi, K., Sumimoto, H., et al. (2003) · Journal of the American Society of Nephrology · doi:10.1097/01.asn.0000077407.90309.65 · Cited by 435 · see citing works
Guzy, R. D., Sharma, B., Bell, E., Chandel, N. S., & Schumacker, P. T. (2008) · Molecular and Cellular Biology · doi:10.1128/mcb.01338-07 · Cited by 427 · see citing works
Reversible Inactivation of HIF-1 Prolyl Hydroxylases Allows Cell Metabolism to Control Basal HIF-1
Lu, H., Dalgard, C. L., Mohyeldin, A., McFate, T., Tait, A. S., & Verma, A. M. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m508718200 · Cited by 400 · see citing works
Ha, H., & Lee, H. B. (2000) · Kidney International · doi:10.1046/j.1523-1755.2000.07704.x · Cited by 311 · see citing works
Wiesener, M. S., Münchenhagen, P., Berger, I., Morgan, N. V., Roigas, J., Schwiertz, A., Jürgensen, J. S., Gruber, G., Maxwell, P. H., Löning, S. A., et al. (2001) · PubMed · Cited by 308 · see citing works
Grubb, R. L., FRANKS, M. E., Toro, J. R., Middelton, L. A., Choyke, L. T., Fowler, S. E., Torres-Cabala, C. A., Glenn, G. M., Choyke, P. L., Merino, M. J., et al. (2007) · The Journal of Urology · doi:10.1016/j.juro.2007.01.155 · Cited by 282 · see citing works
Self-citationXie, H., Valera, V., Merino, M. J., Amato, A. M., Signoretti, S., Linehan, W. M., Sukhatme, V. P., & Seth, P. (2009) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-08-1049 · Cited by 232 · see citing works
Self-citationKoukourakis, M. I., Giatromanolaki, A. N., Simopoulos, C., Polychronidis, A., & Sivridis, E. (2005) · Clinical & Experimental Metastasis · doi:10.1007/s10585-005-2343-7 · Cited by 227 · see citing works
The von Hippel–Lindau protein, HIF hydroxylation, and oxygen sensing
Kaelin, W. G. (2005) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2005.08.165 · Cited by 213 · see citing works
Pyruvate protects mitochondria from oxidative stress in human neuroblastoma SK-N-SH cells
Wang, X., Perez, E., Liu, R., Yan, L., Mallet, R. T., & Yang, S. (2006) · Brain Research · doi:10.1016/j.brainres.2006.11.032 · Cited by 203 · see citing works
A novel inhibitor of glucose uptake sensitizes cells to FAS-induced cell death
Wood, T. E., Dalili, S., Simpson, C. D., Hurren, R., Mao, X., Suárez, F., Gronda, M., Eberhard, Y., Minden, M. D., Bilan, P. J., et al. (2008) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-08-0569 · Cited by 197 · see citing works
Lactate stimulates endothelial cell migration
Beckert, S., Farrahi, F., Aslam, R. S., Scheuenstuhl, H., Königsrainer, A., Hussain, M., & Hunt, T. K. (2006) · Wound Repair and Regeneration · doi:10.1111/j.1743-6109.2006.00127.x · Cited by 187 · see citing works
Pollard, P. J., Spencer‐Dene, B., Shukla, D., Howarth, K. M., Nye, E. L., El-Bahrawy, M. A., Deheragoda, M. G., Kolatsi‐Joannou, M., McDonald, S. A. C., Martin, A., et al. (2007) · Cancer Cell · doi:10.1016/j.ccr.2007.02.005 · Cited by 177 · see citing works
Endothelial cell response to lactate: Implication of PAR modification of VEGF
Kumar, V. B. S., Viji, R. I., Kiran, M. S., & Sudhakaran, P. R. (2006) · Journal of Cellular Physiology · doi:10.1002/jcp.20955 · Cited by 143 · see citing works
Talior, I., Tennenbaum, T., Kuroki, T., & Eldar-Finkelman, H. (2005) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00378.2004 · Cited by 120 · see citing works
NAD(P)H Oxidases Regulate HIF-2α Protein Expression
Block, K. L., Gorin, Y. C., Hoover, P., Williams, P., Chełmicki, T., Clark, R. A., Yoneda, T., & Abboud, H. E. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m611569200 · Cited by 117 · see citing works
Self-citationPollard, P., Wortham, N., Barclay, E., Alam, A., Elia, G., Manek, S., Poulsom, R., & Tomlinson, I. (2005) · The Journal of Pathology · doi:10.1002/path.1686 · Cited by 100 · see citing works
A computational model of intracellular oxygen sensing by hypoxia-inducible factor HIF1α
Qutub, A. A., & Popel, A. S. (2006) · Journal of Cell Science · doi:10.1242/jcs.03087 · Cited by 87 · see citing works
High glucose concentrations and protein kinase C isoforms in vascular smooth muscle cells
Haller, H. G., Baur, E., Quass, P., Lindschau, C., Distler, A., & Luft, F. C. (1995) · Kidney International · doi:10.1038/ki.1995.152 · Cited by 74 · see citing works
HIF and fumarate hydratase in renal cancer
Sudarshan, S., Linehan, W. M., & Neckers, L. (2007) · British Journal of Cancer · doi:10.1038/sj.bjc.6603547 · Cited by 70 · see citing works
Self-citationPithukpakorn, M., Wei, M.-H., Toure, O., Steinbach, P. J., Glenn, G. M., Zbar, B., Linehan, W. M., & Toro, J. R. (2006) · Journal of Medical Genetics · doi:10.1136/jmg.2006.041087 · Cited by 53 · see citing works
Self-citationLee, H. S., Son, S. M., Kim, Y.-K., Hong, K. W., & Kim, C. D. (2003) · Life Sciences · doi:10.1016/s0024-3205(03)00186-3 · Cited by 44 · see citing works
Moriguchi, N., Hinoi, E., Tsuchihashi, Y., Fujimori, S., Iemata, M., Takarada, T., & Yoneda, Y. (2006) · PubMed · doi:10.14670/hh-21.969 · Cited by 23 · see citing works
Kokko, A., Ylisaukko‐oja, S. K., Kiuru, M. H., Takatalo, M. S., Salmikangas, P., Tuimala, J., Arango, D., Karhu, A., Aaltonen, L. A., & Jäntti, J. (2005) · International Journal of Cancer · doi:10.1002/ijc.21423 · Cited by 9 · see citing works
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Majmundar, A. J., Wong, W. J., & Simon, M. C. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.09.022 · Cited by 2,380 · see citing works
Mitochondrial ROS in cancer: initiators, amplifiers or an Achilles' heel?
Sabharwal, S. S., & Schumacker, P. T. (2014) · Nature reviews. Cancer · doi:10.1038/nrc3803 · Cited by 1,643 · see citing works
Comprehensive Molecular Characterization of Papillary Renal-Cell Carcinoma
The Cancer Genome Atlas Research Network (2016) · New England Journal of Medicine · doi:10.1056/nejmoa1505917 · Cited by 1,336 · see citing works
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Sporn, M. B., & Liby, K. T. (2012) · Nature Reviews Cancer · doi:10.1038/nrc3278 · Cited by 1,067 · 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
Mitochondrial reactive oxygen species and cancer
Sullivan, L. B., & Chandel, N. S. (2014) · Cancer & Metabolism · doi:10.1186/2049-3002-2-17 · Cited by 799 · see citing works
The genetic basis of kidney cancer: a metabolic disease
Linehan, W. M., Srinivasan, R., & Schmidt, L. S. (2010) · Nature Reviews Urology · doi:10.1038/nrurol.2010.47 · Cited by 743 · see citing works
Self-citationMitochondria 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
Self-citationHaem oxygenase is synthetically lethal with the tumour suppressor fumarate hydratase
Frezza, C., Zheng, L., Folger, O., Rajagopalan, K. N., MacKenzie, E. D., Jerby, L., Micaroni, M., Chaneton, B., Adam, J., Hedley, A., et al. (2011) · Nature · doi:10.1038/nature10363 · Cited by 503 · see citing works
Pheochromocytoma and paraganglioma pathogenesis: learning from genetic heterogeneity
Dahia, P. L. M. (2014) · Nature Reviews Cancer · doi:10.1038/nrc3648 · Cited by 545 · see citing works
The complexity of the Nrf2 pathway: beyond the antioxidant response
Huang, Y. S., Li, W., Su, Z., & Kong, A. T. (2015) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2015.08.001 · Cited by 449 · see citing works
Altered metabolite levels in cancer: implications for tumour biology and cancer therapy
Sullivan, L. B., Gui, D. Y., & Heiden, M. G. V. (2016) · Nature Reviews Cancer · doi:10.1038/nrc.2016.85 · Cited by 406 · see citing works
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Enzo, E., Santinon, G., Pocaterra, A., Aragona, M., Bresolin, S., Forcato, M., Grifoni, D., Pession, A., Zanconato, F., Guzzo, G., et al. (2015) · The EMBO Journal · doi:10.15252/embj.201490379 · Cited by 414 · see citing works
Genome-wide CRISPRi/a screens in human neurons link lysosomal failure to ferroptosis
Tian, R., Abarientos, A., Hong, J., Hashemi, S. H., Yan, R., Dräger, N., Leng, K., Nalls, M. A., Singleton, A. B., Xu, K., et al. (2021) · Nature Neuroscience · doi:10.1038/s41593-021-00862-0 · Cited by 414 · see citing works
Ooi, A., Wong, J.-C., Petillo, D., Roossien, D., Perrier-Trudova, V., Whitten, D., Min, B. W. H., Tan, M.-H., Zhang, Z., Yang, X. J., et al. (2011) · Cancer Cell · doi:10.1016/j.ccr.2011.08.024 · Cited by 401 · see citing works
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Andrejeva, G., & Rathmell, J. C. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.06.004 · Cited by 368 · see citing works
The Metabolic Basis of Kidney Cancer
Linehan, W. M., Schmidt, L. S., Crooks, D. R., Wei, D., Srinivasan, R., Lang, M., & Ricketts, C. J. (2019) · Cancer Discovery · doi:10.1158/2159-8290.cd-18-1354 · Cited by 336 · see citing works
Self-citationRole of mitochondrial dysfunction in cancer progression
Hsu, C., Tseng, L., & Lee, H. (2016) · Experimental Biology and Medicine · doi:10.1177/1535370216641787 · Cited by 306 · see citing works
The Proto-oncometabolite Fumarate Binds Glutathione to Amplify ROS-Dependent Signaling
Sullivan, L. B., Martinez-Garcia, E., Nguyen, H., Mullen, A. R., Dufour, E., Sudarshan, S., Licht, J. D., Deberardinis, R. J., & Chandel, N. S. (2013) · Molecular Cell · doi:10.1016/j.molcel.2013.05.003 · Cited by 304 · see citing works
Self-citationAiding and abetting roles of NOX oxidases in cellular transformation
Block, K. L., & Gorin, Y. C. (2012) · Nature reviews. Cancer · doi:10.1038/nrc3339 · Cited by 301 · see citing works
Self-citationFumarate induces redox-dependent senescence by modifying glutathione metabolism
Zheng, L., Cardaci, S., Jerby, L., MacKenzie, E. D., Sciacovelli, M., Johnson, T. I., Gaude, E., King, A., Leach, J. D. G., Edrada-Ebel, R., et al. (2015) · Nature Communications · doi:10.1038/ncomms7001 · Cited by 281 · see citing works
Reactive oxygen species-dependent signaling regulates cancer
Weinberg, F. D., & Chandel, N. S. (2009) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-009-0099-y · Cited by 276 · see citing works
Trpkov, K., Hes, O., Agaimy, A., Bonert, M., Martínek, P., Magi‐Galluzzi, C., Kristiansen, G., Lüders, C., Nesi, G., Compérat, É., et al. (2016) · The American Journal of Surgical Pathology · doi:10.1097/pas.0000000000000617 · Cited by 259 · see citing works
Linehan, W. M., & Rouault, T. A. (2013) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-13-0304 · Cited by 223 · see citing works
Self-citationTong, W.-H., Sourbier, C., Kovtunovych, G., Jeong, S. Y., Vira, M., Ghosh, M., Romero, V. V., Sougrat, R., Vaulont, S., Viollet, B., et al. (2011) · Cancer Cell · doi:10.1016/j.ccr.2011.07.018 · Cited by 212 · see citing works
Self-citationYou, Y.-H., Quach, T., Saito, R., Pham, J., & Sharma, K. (2015) · Journal of the American Society of Nephrology · doi:10.1681/asn.2015030302 · Cited by 191 · see citing works
The emerging role of fumarate as an oncometabolite
Yang, M., Soga, T., Pollard, P. J., & Adam, J. (2012) · Frontiers in Oncology · doi:10.3389/fonc.2012.00085 · Cited by 189 · see citing works
Molecular Diagnosis and Therapy of Kidney Cancer
Linehan, W. M., Bratslavsky, G., Pinto, P. A., Schmidt, L. S., Neckers, L., Bottaro, D. P., & Srinivasan, R. (2010) · Annual Review of Medicine · doi:10.1146/annurev.med.042808.171650 · Cited by 166 · see citing works
Self-citationTCA Cycle Defects and Cancer: When Metabolism Tunes Redox State
Cardaci, S., & Ciriolo, M. R. (2012) · International Journal of Cell Biology · doi:10.1155/2012/161837 · Cited by 162 · see citing works
State of the Science: An Update on Renal Cell Carcinoma
Jonasch, E. W., Futreal, P. A., Davis, I. J., Bailey, S. T., Kim, W. Y., Brugarolas, J., Giaccia, A. J., Kurban, G., Pause, A., Frydman, J., et al. (2012) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-12-0117 · Cited by 161 · see citing works
Kaelin, W. G. (2011) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.2011.76.010975 · Cited by 161 · see citing works
Dimethyl fumarate, a two‐edged drug: Current status and future directions
Saidu, N. E. B., Kavian, N., Leroy, K., Jacob, C., Nicco, C., Batteux, F., & Alexandre, J. (2019) · Medicinal Research Reviews · doi:10.1002/med.21567 · Cited by 160 · see citing works
Hereditary leiomyomatosis and renal cell cancer: update on clinical and molecular characteristics
Lehtonen, H. J. (2011) · Familial Cancer · doi:10.1007/s10689-011-9428-z · Cited by 154 · see citing works
Speer, R. E., Karuppagounder, S. S., Basso, M., Sleiman, S. F., Kumar, A., Brand, D., Smirnova, N., Gazaryan, I. G., Khim, S. J., & Ratan, R. R. (2013) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2013.01.026 · Cited by 155 · see citing works
Teicher, B. A., Linehan, W. M., & Helman, L. J. (2012) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-12-2587 · Cited by 152 · see citing works
Self-citationEpidemiology and Prevention of Renal Cell Carcinoma
Makino, T., Kadomoto, S., Izumi, K., & Mizokami, A. (2022) · Cancers · doi:10.3390/cancers14164059 · Cited by 151 · see citing works
Inborn and acquired metabolic defects in cancer
Frezza, C., Pollard, P. J., & Gottlieb, E. (2011) · Journal of Molecular Medicine · doi:10.1007/s00109-011-0728-4 · Cited by 146 · see citing works
Gardie, B., Remenieras, A., Kattygnarath, D., Bombled, J., Lefèvre, S.-H., Perrier-Trudova, V., Rustin, P., Barrois, M., Slama, A., Avril, M., et al. (2011) · Journal of Medical Genetics · doi:10.1136/jmg.2010.085068 · Cited by 143 · see citing works
Yang, Y., Valera, V., Padilla‐Nash, H. M., Sourbier, C., Vocke, C. D., Vira, M. A., Abu-Asab, M. S., Bratslavsky, G., Tsokos, M., Merino, M. J., et al. (2009) · Cancer Genetics and Cytogenetics · doi:10.1016/j.cancergencyto.2009.08.018 · Cited by 139 · see citing works
Self-citationSanz‐Ortega, J., Vocke, C. D., Stratton, P., Linehan, W. M., & Merino, M. J. (2012) · The American Journal of Surgical Pathology · doi:10.1097/pas.0b013e31825ec16f · Cited by 132 · see citing works
Self-citationIsocitrate dehydrogenases in physiology and cancer: biochemical and molecular insight
Al‐Khallaf, H. (2017) · Cell & Bioscience · doi:10.1186/s13578-017-0165-3 · Cited by 127 · see citing works
HIF-1 Mediates Renal Fibrosis in OVE26 Type 1 Diabetic Mice
Nayak, B. K., Shanmugasundaram, K., Friedrichs, W. E., Cavaglierii, R. C., Patel, M., Barnes, J. L., & Block, K. L. (2016) · Diabetes · doi:10.2337/db15-0519 · Cited by 124 · see citing works
Self-citationA chemoproteomic portrait of the oncometabolite fumarate
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Self-citationO′Flaherty, L., Adam, J., Heather, L. C., Zhdanov, A. V., Chung, Y., Miranda, M. X., Croft, J., Olpin, S. E., Clarke, K. J., Pugh, C. W., et al. (2010) · Human Molecular Genetics · doi:10.1093/hmg/ddq305 · Cited by 108 · see citing works
Targeting ABL1-Mediated Oxidative Stress Adaptation in Fumarate Hydratase-Deficient Cancer
Sourbier, C., Ricketts, C. J., Matsumoto, S., Crooks, D. R., Liao, P., Mannes, P. Z., Yang, Y., Wei, M.-H., Srivastava, G. K., Ghosh, S., et al. (2014) · Cancer Cell · doi:10.1016/j.ccell.2014.10.005 · Cited by 108 · see citing works
Self-citationNew Strategies in Renal Cell Carcinoma: Targeting the Genetic and Metabolic Basis of Disease
Srinivasan, R., Ricketts, C. J., Sourbier, C., & Linehan, W. M. (2015) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-13-2993 · Cited by 108 · see citing works
Self-citationIntegrated Molecular Characterization of Fumarate Hydratase–deficient Renal Cell Carcinoma
Sun, G., Zhang, X., Liang, J., Pan, X., Zhu, S., Liu, Z., Armstrong, C. M., Chen, J., Lin, W., Liao, B., et al. (2021) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-20-3788 · Cited by 102 · see citing works
Yang, Y., Lane, A. N., Ricketts, C. J., Sourbier, C., Wei, M.-H., Shuch, B. M., Pike, L. S., Wu, M., Rouault, T. A., Boros, L. G., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0072179 · Cited by 103 · see citing works
Self-citationCancer cell metabolism and the modulating effects of nitric oxide
Chang, C.-F., Diers, A. R., & Hogg, N. (2014) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2014.11.012 · Cited by 101 · see citing works
A role for cytosolic fumarate hydratase in urea cycle metabolism and renal neoplasia
Adam, J., Yang, M., Bauerschmidt, C., Kitagawa, M., O’Flaherty, L., Maheswaran, P., Özkan, G., Sahgal, N., Baban, D., Kato, K., et al. (2013) · Cell Reports · doi:10.1016/j.celrep.2013.04.006 · Cited by 97 · see citing works
Metabolic alterations in renal cell carcinoma
Massari, F., Ciccarese, C., Santoni, M., Brunelli, M., Piva, F., Modena, A., Bimbatti, D., Fantinel, E., Santini, D., Liang Cheng, C., et al. (2015) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2015.07.002 · Cited by 97 · see citing works
Metabolic dysfunction in pulmonary hypertension: the expanding relevance of the W arburg effect
Cottrill, K. A., & Chan, S. Y. (2013) · European Journal of Clinical Investigation · doi:10.1111/eci.12104 · Cited by 94 · see citing works
Wangpaichitr, M., Sullivan, E. J., Theodoropoulos, G., Wu, C., You, M., Feun, L. G., Lampidis, T. J., Kuo, M. T., & Savaraj, N. (2012) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-11-0599 · Cited by 94 · see citing works
Aerobic glycolysis: a novel target in kidney cancer
Shuch, B. M., Linehan, W. M., & Srinivasan, R. (2013) · Expert Review of Anticancer Therapy · doi:10.1586/era.13.57 · Cited by 92 · see citing works
Self-citationRare insights into cancer biology
Adam, J., Yang, M., Soga, T., & Pollard, P. J. (2013) · Oncogene · doi:10.1038/onc.2013.222 · Cited by 88 · see citing works
HIF-1α as a central mediator of cellular resistance to intracellular pathogens
Knight, M., & Stanley, S. A. (2019) · Current Opinion in Immunology · doi:10.1016/j.coi.2019.05.005 · Cited by 86 · see citing works
Advances in hereditary leiomyomatosis and renal cell carcinoma (HLRCC) research
Ooi, A. (2019) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2019.10.016 · Cited by 83 · see citing works
Emerging Metabolic Targets in Cancer Therapy
Zhao, Y. (2010) · Frontiers in bioscience · doi:10.2741/3826 · Cited by 82 · see citing works
Valbuena, G. N., Rizzardini, M., Cimini, S., Siskos, A., Bendotti, C., Cantoni, L., & Keun, H. C. (2015) · Molecular Neurobiology · doi:10.1007/s12035-015-9165-7 · Cited by 81 · see citing works
Adrenal Nodular Hyperplasia in Hereditary Leiomyomatosis and Renal Cell Cancer
Shuch, B. M., Ricketts, C. J., Vocke, C. D., Valera, V., Chen, C. C., Gautam, R., Gupta, G. N., Gómez-Macias, G. S., Merino, M. J., Bratslavsky, G., et al. (2012) · The Journal of Urology · doi:10.1016/j.juro.2012.07.139 · Cited by 79 · see citing works
Self-citationBuelow, B., Cohen, J. N., Nagymányoki, Z., Frizzell, N., Joseph, N. M., McCalmont, T. H., & Garg, K. (2016) · The American Journal of Surgical Pathology · doi:10.1097/pas.0000000000000626 · Cited by 79 · see citing works
Ge, X., Li, M.-D., Yin, J.-X., Shi, Z.-M., Fu, Y., Zhao, N.-W., Chen, H., Meng, L., Li, X., Hu, Z., et al. (2022) · Molecules and Cells · doi:10.1016/j.molcel.2022.01.029 · Cited by 67 · see citing works
Metabolism of Kidney Cancer: From the Lab to Clinical Practice
Sudarshan, S., Karam, J. A., Brugarolas, J., Thompson, R. H., Uzzo, R. G., Rini, B. I., Margulis, V., Patard, J., Escudier, B. J., & Linehan, W. M. (2012) · European Urology · doi:10.1016/j.eururo.2012.09.054 · Cited by 79 · see citing works
Self-citationMetabolic Alterations in Cancer and Their Potential as Therapeutic Targets
Weyandt, J. D., Thompson, C. B., Giaccia, A. J., & Rathmell, W. K. (2017) · American Society of Clinical Oncology Educational Book · doi:10.1200/edbk_175561 · Cited by 75 · see citing works
Inter‐connection between mitochondria and HIFs
Tormos, K. V., & Chandel, N. S. (2010) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2010.01031.x · Cited by 75 · see citing works
Downregulation of PCK2 remodels tricarboxylic acid cycle in tumor-repopulating cells of melanoma
Luo, S., Li, Y., Ma, R., Liu, J., Xu, P., Zhang, H.-B., Tang, K., Ma, J., Liu, N., Zhang, Y., et al. (2017) · Oncogene · doi:10.1038/onc.2016.520 · Cited by 74 · see citing works
Wu, C., Wyatt, A. W., Lapuk, A. V., McPherson, A., McConeghy, B. J., Bell, R. H., Anderson, S. A., Haegert, A. M., Brahmbhatt, S., Shukin, R. J., et al. (2012) · The Journal of Pathology · doi:10.1002/path.3987 · Cited by 73 · see citing works
Preston, R. S., Philp, A., Claessens, T., Gijezen, L., Dydensborg, A. B., Dunlop, E. A., Harper, K., Brinkhuizen, T., Menko, F. H., Davies, D. M., et al. (2010) · Oncogene · doi:10.1038/onc.2010.497 · Cited by 72 · see citing works
Ashrafian, H., O′Flaherty, L., Adam, J., Steeples, V., Chung, Y., East, P., Vanharanta, S., Lehtonen, H. J., Nye, E. L., Hatipoglu, E., et al. (2010) · Cancer Research · doi:10.1158/0008-5472.can-10-1949 · Cited by 72 · see citing works
Wang, F., Liang, R., Tandon, N., Matthews, E. R., Shrestha, S., Yang, J., Soibam, B., Yang, J., & Liu, Y. (2018) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-018-2971-0 · Cited by 71 · see citing works
Metabolic Pathways in Kidney Cancer: Current Therapies and Future Directions
Rathmell, W. K., Rathmell, J. C., & Linehan, W. M. (2018) · Journal of Clinical Oncology · doi:10.1200/jco.2018.79.2309 · Cited by 64 · see citing works
Self-citationPrecision medicine from the renal cancer genome
Riazalhosseini, Y., & Lathrop, M. G. (2016) · Nature Reviews Nephrology · doi:10.1038/nrneph.2016.133 · Cited by 69 · see citing works
Hoerner, C. R., Chen, V. J., & Fan, A. C. (2019) · Kidney Cancer · doi:10.3233/kca-180043 · Cited by 68 · see citing works
Balancing biosynthesis and bioenergetics: metabolic programs in oncogenesis
Barger, J. F., & Plas, D. R. (2010) · Endocrine Related Cancer · doi:10.1677/erc-10-0106 · Cited by 65 · see citing works
SDH5 mutations and familial paraganglioma: somewhere Warburg is smiling
Kaelin, W. G. (2009) · Cancer Cell · doi:10.1016/j.ccr.2009.08.013 · Cited by 67 · see citing works
Li, J., Wang, Q., Yang, Y., Lei, C., Yang, F., Liang, L., Chen, C., Xia, J. L., Wang, K., & Tang, N. (2019) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-019-1459-6 · Cited by 66 · see citing works
Self-citationYang, Y., Valera, V., Sourbier, C., Vocke, C. D., Wei, M., Pike, L., Huang, Y. K., Merino, M. A., Bratslavsky, G., Wu, M., et al. (2012) · Cancer Genetics · doi:10.1016/j.cancergen.2012.05.001 · Cited by 65 · see citing works
Self-citationNew Insights into the Biology of Renal Cell Carcinoma
Li, L., & Kaelin, W. G. (2011) · Hematology/Oncology Clinics of North America · doi:10.1016/j.hoc.2011.04.004 · Cited by 62 · see citing works
Zhang, C., Cao, S., Toole, B. P., & Xu, Y. (2014) · International Journal of Cancer · doi:10.1002/ijc.28975 · Cited by 63 · see citing works
Shanmugasundaram, K., Nayak, B., Shim, E., Livi, C. B., Block, K. L., & Sudarshan, S. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.568162 · Cited by 60 · see citing works
Self-citationWang, P., Mai, C., Wei, Y.-L., Zhao, J.-J., Hu, Y.-M., Zeng, Z.-L., Yang, J., Lu, W.-H., Xu, R., & Huang, P. (2013) · Medical Oncology · doi:10.1007/s12032-013-0552-5 · Cited by 60 · see citing works
LncRNA‐TP53TG1 Participated in the Stress Response Under Glucose Deprivation in Glioma
Chen, X., Gao, Y., Li, D., Cao, Y., & Hao, B. (2017) · Journal of Cellular Biochemistry · doi:10.1002/jcb.26175 · Cited by 59 · see citing works
Sun, Y., Bandi, M. L., Lofton, T. E., Smith, M. G., Bristow, C. A., Carugo, A., Rogers, N. E., Leonard, P. G., Chang, Q., Mullinax, R. A., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2018.12.043 · Cited by 59 · see citing works
Zhang, C., Liu, Q., Li, M., Lin, S., Peng, Y., Wu, D., Li, T. Y., Fu, Q., Jia, W., Wang, X., et al. (2015) · Cell Research · doi:10.1038/cr.2015.90 · Cited by 55 · see citing works
Zheleznova, N. N., Yang, C., Ryan, R. P., Halligan, B. D., Liang, M., Greene, A. S., & Cowley, A. W. (2012) · Physiological Genomics · doi:10.1152/physiolgenomics.00060.2012 · Cited by 54 · see citing works
The Tricarboxylic Acid Cycle Metabolites for Cancer: Friend or Enemy
Wu, J., Liu, N., Chen, J., Tao, Q., Li, Q., Li, J., Chen, X., & Peng, C. (2024) · Research · doi:10.34133/research.0351 · Cited by 57 · see citing works
Gaster, M., Nehlin, J. O., & Minet, A. D. (2012) · Archives of Physiology and Biochemistry · doi:10.3109/13813455.2012.656653 · Cited by 53 · see citing works
Wang, J., Zhang, P., Zhong, J., Tan, M., Ge, J., Tao, L., Li, Y., Zhu, Y., Wu, L., Qiu, J., et al. (2016) · Oncotarget · doi:10.18632/oncotarget.8382 · Cited by 52 · see citing works
Cao, F., Liang, K., Tang, W., Ni, Q.-Y., Ji, Z., Zha, C.-K., Wang, Y., Jiang, Z., Hou, S., Tao, L., et al. (2024) · Journal of Controlled Release · doi:10.1016/j.jconrel.2024.06.047 · Cited by 52 · see citing works
Exploring a glycolytic inhibitor for the treatment of an FH-deficient type-2 papillary RCC
Yamasaki, T., Tran, T. A. T., Öz, O. K., Raj, G. V., Schwarz, R. E., DeBerardinis, R. J., Zhang, X., & Brugarolas, J. (2011) · Nature Reviews Urology · doi:10.1038/nrurol.2010.234 · Cited by 52 · see citing works
Sudarshan, S., Shanmugasundaram, K., Naylor, S. L., Lin, S., Livi, C. B., O’Neill, C. F., Parekh, D. J., Yeh, I., Sun, L., & Block, K. L. (2011) · PLoS ONE · doi:10.1371/journal.pone.0021037 · Cited by 52 · see citing works
Self-citationTargeted therapeutic strategies for the management of renal cell carcinoma
Singer, E. A., Gupta, G. N., & Srinivasan, R. (2012) · Current Opinion in Oncology · doi:10.1097/cco.0b013e328351c646 · Cited by 51 · see citing works
Liu, J., Hanavan, P. D., Kras, K. A., Ruiz, Y. W., Castle, E. P., Lake, D. F., Chen, X., O’Brien, D. R., Luo, H., Robertson, K. D., et al. (2018) · Journal of Proteome Research · doi:10.1021/acs.jproteome.8b00628 · Cited by 48 · see citing works
Progress of stimulus responsive nanosystems for targeting treatment of bacterial infectious diseases
Yang, N., Sun, M., Wang, H., Hu, D., Zhang, A., Khan, S., Chen, Z., Chen, D., & Xie, S. (2024) · Advances in Colloid and Interface Science · doi:10.1016/j.cis.2024.103078 · Cited by 46 · see citing works
Leiomyoma Cutis: A Focused Review on Presentation, Management, and Association with Malignancy
Malik, K., Patel, P. S., Chen, J., & Khachemoune, A. (2015) · American Journal of Clinical Dermatology · doi:10.1007/s40257-015-0112-1 · Cited by 45 · see citing works
PI3K regulation of the SKP-2/p27 axis through mTORC2
Shanmugasundaram, K., Block, K. L., Nayak, B. K., Livi, C. B., Venkatachalam, M. A., & Sudarshan, S. (2012) · Oncogene · doi:10.1038/onc.2012.226 · Cited by 44 · see citing works
Self-citationThe NADPH Oxidase Subunit p22 Inhibits the Function of the Tumor Suppressor Protein Tuberin
Block, K. L., Gorin, Y. C., New, D. D., Eid, A. A., Chełmicki, T., Reed, A. B., Choudhury, G. G., Parekh, D. J., & Abboud, H. E. (2010) · American Journal Of Pathology · doi:10.2353/ajpath.2010.090606 · Cited by 43 · see citing works
Self-citationHirsch, M. S., Signoretti, S., & Cin, P. D. (2015) · Surgical pathology clinics · doi:10.1016/j.path.2015.09.003 · Cited by 43 · see citing works
- Authors
- Sudarshan, S., Sourbier, C., Kong, H.-S., Block, K., Romero, V. A. V., Yang, Y., Galindo, C., Mollapour, M., Scroggins, B., Goode, N., Lee, M.-J., Gourlay, C. W., Trepel, J., Linehan, W. M., & Neckers, L.
- Affiliations
- National Institutes of Health (US)
- The University of Texas at San Antonio Health Science Center (US)
- Urologic Oncology Branch, National Cancer Institute, Bethesda, Maryland 20892
- University of Kent (GB)
- Corresponding author
- Neckers, Len
- ORCID
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2009-08-01
- Volume
- 29
- Issue
- 15
- Pages
- 4080-4090
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC2715796
- OpenAlex
- W2098189012
- Cited by
- 217
- References
- 43
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 8 · 2023: 8 · 2022: 9 · 2021: 13 · 2020: 11 · 2019: 15 · 2018: 13 · 2017: 10 · 2016: 14 · 2015: 15 · 2014: 12 · 2013: 16 · 2012: 31
- FWCI
- 7.50
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular and Cellular Biology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Kent Academic Repository (University of Kent) (submittedVersion)
- Funders
- Association for the Study of Animal Behaviour
- National Institutes of Health
- National Cancer Institute (R01CA131272, Z01SC006659, Z01BC010683)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Renal cell carcinoma treatment
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Ferroptosis and cancer prognosis
- Keywords
- fumarate hydratase deficiency, hereditary leiomyomatosis and renal cell carcinoma, HIF-1α stabilization, reactive oxygen species, pseudohypoxia, prolyl hydroxylation, VHL, renal cell carcinoma, TCA cycle, glucose metabolism
- MeSH terms
- Cell Line, Fumarate Hydratase, Glucose, Glycolysis, Humans, Kidney Neoplasms, Multienzyme Complexes, NADH, NADPH Oxidoreductases, Blotting, Western, Reactive Oxygen Species, Oxidative Stress, RNA Interference, Cell Line, Tumor, Protein Kinase C-delta, Hypoxia-Inducible Factor 1, alpha Subunit
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