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Mitochondrial metabolism and ROS generation are essential for Kras-mediated tumorigenicity
Open accessAbstract
Otto Warburg's theory on the origins of cancer postulates that tumor cells have defects in mitochondrial oxidative phosphorylation and therefore rely on high levels of aerobic glycolysis as the major source of ATP to fuel cellular proliferation (the Warburg effect). This is in contrast to normal cells, which primarily utilize oxidative phosphorylation for growth and survival. Here we report that the major function of glucose metabolism for Kras-induced anchorage-independent growth, a hallmark of transformed cells, is to support the pentose phosphate pathway. The major function of glycolytic ATP is to support growth under hypoxic conditions. Glutamine conversion into the tricarboxylic acid cycle intermediate alpha-ketoglutarate through glutaminase and alanine aminotransferase is essential for Kras-induced anchorage-independent growth. Mitochondrial metabolism allows for the generation of reactive oxygen species (ROS) which are required for Kras-induced anchorage-independent growth through regulation of the ERK MAPK signaling pathway. We show that the major source of ROS generation required for anchorage-independent growth is the Q o site of mitochondrial complex III. Furthermore, disruption of mitochondrial function by loss of the mitochondrial transcription factor A (TFAM) gene reduced tumorigenesis in an oncogenic Kras-driven mouse model of lung cancer. These results demonstrate that mitochondrial metabolism and mitochondrial ROS generation are essential for Kras-induced cell proliferation and tumorigenesis.
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“Providing cells with αKG, oxaloacetate, or pyruvate is sufficient to rescue cancer cell proliferation in conditions of glutamine starvation, confirming that glutamine supports proliferation by replenishing depleted TCA cycle intermediates, a process termed anaplerosis (Altman et al., 2016; Weinberg et al., 2010; Yuneva et al., 2007).”
From Targeting Metabolism for Cancer Therapy (2017) · cites this paper as Weinberg et al., 2010
In the citing paper
“However, KRAS has also been shown to promote cancer cell growth by stimulating alanine aminotransferase activity, leading to high levels of α-ketoglutarate for the TCA cycle and mitochondrial ROS generation, which was required for mutant KRAS-driven tumorigenesis in a mouse model of lung cancer64.”
From The metabolic landscape of RAS-driven cancers from biology to therapy (2021) · cites this paper as [64]
In the citing paper
“A low level of reactive oxygen species (ROS) activates tumorigenic growth signaling; however, when the level exceeds the cellular redox capacity, ROS can damage macromolecules such as proteins, lipids and nucleotides55.”
From Glutamine reliance in cell metabolism (2020) · cites this paper as [55]
In the citing paper
“Correspondingly, in K-Ras mutant cells, the oxygen consumption rate and ATP generation are enhanced by glutamine, contributing to tumorigenesis55.”
From Glutamine reliance in cell metabolism (2020) · cites this paper as [55]
In the citing paper
“Notably, alanine levels were significantly decreased in Mpc knockdown cells, highlighting a role for mitochondrial pyruvate and mitochondrial alanine aminotransferase (ALT2) in mediating glutamine anaplerosis which was previously described in cancer cells (Weinberg et al., 2010).”
From Regulation of Substrate Utilization by the Mitochondrial Pyruvate Carrier (2014) · cites this paper as Weinberg et al., 2010
In the citing paper
“Another study reported that mitochondrial ROS are necessary for the KRAS (Kirsten rat sarcoma virus)—induced anchored-independent growth of lung cancer.”
From Reactive Oxygen Species, Toxicity, Oxidative Stress, and Antioxidants: Chronic Diseases and Aging (2023) · cites this paper as Weinberg et al. 2010
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Citations
Cites
Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation
Vander Heiden, M. G., Cantley, L. C., & Thompson, C. B. (2009) · Science · doi:10.1126/science.1160809 · Cited by 16,197
Warburg, O. (1956) · Science · doi:10.1126/science.123.3191.309 · Cited by 13,425
The Biology of Cancer: Metabolic Reprogramming Fuels Cell Growth and Proliferation
DeBerardinis, R. J., Lum, J. J., Hatzivassiliou, G., & Thompson, C. B. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2007.10.002 · Cited by 4,088
On Respiratory Impairment in Cancer Cells
Warburg, O. H. (1956) · Science · doi:10.1126/science.124.3215.269 · Cited by 3,472
The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth
Christofk, H. R., Vander Heiden, M. G., Harris, M. H., Ramanathan, A., Gerszten, R. E., Wei, R., Fleming, M. D., Schreiber, S. L., & Cantley, L. C. (2008) · Nature · doi:10.1038/nature06734 · Cited by 2,820
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
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
Wise, D. R., DeBerardinis, R. J., Mancuso, A., Sayed, N., Zhang, X.-Y., Pfeiffer, H. K., Nissim, I., Daikhin, E., Yudkoff, M., McMahon, S. B., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0810199105 · Cited by 2,001
Hypoxia, HIF1 and glucose metabolism in the solid tumour
Denko, N. C. (2008) · Nature Reviews Cancer · doi:10.1038/nrc2468 · Cited by 1,707
Fantin, V. R., St-Pierre, J., & Leder, P. (2006) · Cancer Cell · doi:10.1016/j.ccr.2006.04.023 · Cited by 1,635
Flagged first, then by citations
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ROS function in redox signaling and oxidative stress
Schieber, M., & Chandel, N. S. (2014) · Current Biology · doi:10.1016/j.cub.2014.03.034 · Cited by 6,931
Self-citationMitochondrial Reactive Oxygen Species (ROS) and ROS-Induced ROS Release
Zorov, D. B., Juhaszova, M., & Sollott, S. J. (2014) · Physiological Reviews · doi:10.1152/physrev.00026.2013 · Cited by 5,383
Regulation of cancer cell metabolism
Cairns, R. A., Harris, I. S., & Mak, T. W. (2011) · Nature Reviews Cancer · doi:10.1038/nrc2981 · Cited by 4,744
Mittler, R. (2017) · Trends in Plant Science · doi:10.1016/j.tplants.2016.08.002 · Cited by 3,499
Otto Warburg's contributions to current concepts of cancer metabolism
Koppenol, W. H., Bounds, P. L., & Dang, C. V. (2011) · Nature Reviews Cancer · doi:10.1038/nrc3038 · Cited by 3,427
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
Fundamentals of Cancer Metabolism
DeBerardinis, R. J., & Chandel, N. S. (2016) · Science Advances · doi:10.1126/sciadv.1600200 · Cited by 3,013
Self-citationReactive Oxygen Species, Toxicity, Oxidative Stress, and Antioxidants: Chronic Diseases and Aging
Jomova, K., Raptova, R., Alomar, S. Y., Alwasel, S. H., Nepovimova, E., Kuca, K., & Valko, M. (2023) · Archives of Toxicology · doi:10.1007/s00204-023-03562-9 · Cited by 2,638
Wallace, D. C. (2012) · Nature Reviews Cancer · doi:10.1038/nrc3365 · Cited by 2,404
Understanding the Intersections between Metabolism and Cancer Biology
Heiden, M. G. V., & DeBerardinis, R. J. (2017) · Cell · doi:10.1016/j.cell.2016.12.039 · Cited by 2,369
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
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
The PI3K–AKT network at the interface of oncogenic signalling and cancer metabolism
Hoxhaj, G., & Manning, B. D. (2020) · Nature Reviews Cancer · doi:10.1038/s41568-019-0216-7 · Cited by 2,137
Oncogenic Kras maintains pancreatic tumors through regulation of anabolic glucose metabolism
Ying, H., Kimmelman, A. C., Lyssiotis, C. A., Hua, S., Chu, G. C., Fletcher-Sananikone, E., Locasale, J. W., Son, J., Zhang, H., Coloff, J. L., et al. (2012) · Cell · doi:10.1016/j.cell.2012.01.058 · Cited by 2,043
Glutamine supports pancreatic cancer growth through a KRAS-regulated metabolic pathway
Son, J., Lyssiotis, C. A., Ying, H., Wang, X., Hua, S., Ligorio, M., Perera, R. M., Ferrone, C. R., Mullarky, E., Shyh-Chang, N., et al. (2013) · Nature · doi:10.1038/nature12040 · Cited by 1,990
Drugging the undruggable RAS: Mission Possible?
Cox, A. D., Fesik, S. W., Kimmelman, A. C., Luo, J., & Der, C. J. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4389 · Cited by 1,997
Mitochondrial DNA stress primes the antiviral innate immune response
West, A. P., Khoury-Hanold, W., Staron, M., Tal, M. C., Pineda, C. M., Lang, S. M., Bestwick, M., Duguay, B. A., Raimundo, N., MacDuff, D. A., et al. (2015) · Nature · doi:10.1038/nature14156 · Cited by 1,975
Reductive glutamine metabolism by IDH1 mediates lipogenesis under hypoxia
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., et al. (2012) · Nature · doi:10.1038/nature10602 · Cited by 1,791
Metabolic Pathways in Immune Cell Activation and Quiescence
Pearce, E. L., & Pearce, E. J. (2013) · Immunity · doi:10.1016/j.immuni.2013.04.005 · Cited by 1,692
Deconvoluting the context-dependent role for autophagy in cancer
White, E. (2012) · Nature reviews. Cancer · doi:10.1038/nrc3262 · Cited by 1,758
Zielonka, J., Joseph, J., Sikora, A., Hardy, M., Ouari, O., Vasquez-Vivar, J., Cheng, G., Lopez, M., & Kalyanaraman, B. (2017) · Chemical Reviews · doi:10.1021/acs.chemrev.7b00042 · Cited by 1,683
Self-citationThe return of metabolism: biochemistry and physiology of the pentose phosphate pathway
Stincone, A., Prigione, A., Cramer, T., Wamelink, M. M. C., Campbell, K., Cheung, E., Olin‐Sandoval, V., Grüning, N., Krüger, A., Tauqeer Alam, M., et al. (2015) · Biological Reviews · doi:10.1111/brv.12140 · Cited by 1,576
Autophagy and autophagy-related proteins in cancer
Li, X., He, S., & Ma, B. (2020) · Molecular Cancer · doi:10.1186/s12943-020-1138-4 · Cited by 1,684
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 1,681
The role of ROS in tumour development and progression
Cheung, E. C., & Vousden, K. H. (2022) · Nature reviews. Cancer · doi:10.1038/s41568-021-00435-0 · Cited by 1,663
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
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
Metabolic pathways promoting cancer cell survival and growth
Boroughs, L. K., & DeBerardinis, R. J. (2015) · Nature Cell Biology · doi:10.1038/ncb3124 · Cited by 1,492
Targeting mitochondria metabolism for cancer therapy
Weinberg, S. E., & Chandel, N. S. (2014) · Nature Chemical Biology · doi:10.1038/nchembio.1712 · Cited by 1,420
Self-citationSena, L. A., Li, S., Jairaman, A., Prakriya, M., Ezponda, T., Hildeman, D. A., Wang, C.-R., Schumacker, P. T., Licht, J. D., Perlman, H., et al. (2013) · Immunity · doi:10.1016/j.immuni.2012.10.020 · Cited by 1,338
Self-citationThe role for autophagy in cancer
White, E. (2015) · Journal of Clinical Investigation · doi:10.1172/jci73941 · Cited by 1,332
Reductive carboxylation supports growth in tumour cells with defective mitochondria
Mullen, A. R., Wheaton, W. W., Jin, E. S., Chen, P.-H., Sullivan, L. B., Cheng, T., Yang, Y., Linehan, W. M., Chandel, N. S., & DeBerardinis, R. J. (2012) · Nature · doi:10.1038/nature10642 · Cited by 1,328
Self-citationActivated Ras requires autophagy to maintain oxidative metabolism and tumorigenesis
Guo, J. Y., Chen, H.-Y., Mathew, R., Fan, J., Strohecker, A. M., Karsli-Uzunbas, G., Kamphorst, J. J., Chen, G., Lemons, J. M. S., Karantza, V., et al. (2011) · Genes & Development · doi:10.1101/gad.2016311 · Cited by 1,323
Zong, W., Rabinowitz, J. D., & White, E. (2016) · Molecular Cell · doi:10.1016/j.molcel.2016.02.011 · Cited by 1,330
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Porporato, P. E., Filigheddu, N., Pedro, J. M. B., Kroemer, G., & Galluzzi, L. (2017) · Cell Research · doi:10.1038/cr.2017.155 · Cited by 1,323
Anastasiou, D., Poulogiannis, G., Asara, J. M., Boxer, M. B., Jiang, J., Shen, M., Bellinger, G., Sasaki, A. T., Locasale, J. W., Auld, D. S., et al. (2011) · Science · doi:10.1126/science.1211485 · Cited by 1,218
Supporting aspartate biosynthesis is an essential function of respiration in proliferating cells
Sullivan, L. B., Gui, D. Y., Hosios, A. M., Bush, L. N., Freinkman, E., & Vander Heiden, M. G. (2015) · Cell · doi:10.1016/j.cell.2015.07.017 · Cited by 1,173
The updated landscape of tumor microenvironment and drug repurposing
Jin, M.-Z., & Jin, W.-L. (2020) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-00280-x · Cited by 1,262
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 1,182
Oxidative Phosphorylation as an Emerging Target in Cancer Therapy
Ashton, T. M., McKenna, W. G., Kunz‐Schughart, L. A., & Higgins, G. S. (2018) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-17-3070 · Cited by 1,177
Metformin inhibits mitochondrial complex I of cancer cells to reduce tumorigenesis
Wheaton, W. W., Weinberg, S. E., Hamanaka, R. B., Soberanes, S., Sullivan, L. B., Anso, E., Glasauer, A., Dufour, E., Mutlu, G. M., Budigner, G. S., et al. (2014) · eLife · doi:10.7554/elife.02242 · Cited by 1,105
Self-citationZandalinas, S. I., Fritschi, F., & Mittler, R. (2021) · Trends in Plant Science · doi:10.1016/j.tplants.2021.02.011 · Cited by 1,193
Metabolic regulation of cell growth and proliferation
Zhu, J., & Thompson, C. B. (2019) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-019-0123-5 · Cited by 1,140
Brand, M. D. (2016) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2016.04.001 · Cited by 1,063
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
Targeting Metabolism for Cancer Therapy
Luengo, A., Gui, D. Y., & Vander Heiden, M. G. (2017) · Cell Chemical Biology · doi:10.1016/j.chembiol.2017.08.028 · Cited by 971
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
How cancer metabolism is tuned for proliferation and vulnerable to disruption
Schulze, A., & Harris, A. L. (2012) · Nature · doi:10.1038/nature11706 · Cited by 945
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
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Kennedy, L., Sandhu, J. K., Harper, M.-E., & Cuperlovic-Culf, M. (2020) · Biomolecules · doi:10.3390/biom10101429 · Cited by 880
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Leone, R. D., & Powell, J. D. (2020) · Nature Reviews Cancer · doi:10.1038/s41568-020-0273-y · Cited by 877
We need to talk about the Warburg effect
DeBerardinis, R. J., & Chandel, N. S. (2020) · Nature Metabolism · doi:10.1038/s42255-020-0172-2 · Cited by 887
Self-citationOncogenic BRAF Regulates Oxidative Metabolism via PGC1α and MITF
Haq, R., Shoag, J., Andreu-Perez, P., Yokoyama, S., Edelman, H., Rowe, G. C., Frederick, D. T., Hurley, A. D., Nellore, A., Kung, A. L., et al. (2013) · Cancer Cell · doi:10.1016/j.ccr.2013.02.003 · Cited by 818
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Murphy, M. P., & Hartley, R. C. (2018) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2018.174 · Cited by 846
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Yang, H., Villani, R. M., Wang, H., Simpson, M. J., Roberts, M. S., Tang, M., & Liang, X. (2018) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-018-0909-x · Cited by 794
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Sullivan, L. B., & Chandel, N. S. (2014) · Cancer & Metabolism · doi:10.1186/2049-3002-2-17 · Cited by 826
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Davidson, S. M., Papagiannakopoulos, T., Olenchock, B. A., Heyman, J. E., Keibler, M. A., Luengo, A., Bauer, M. R., Jha, A. K., O’Brien, J. P., Pierce, K. A., et al. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.01.007 · Cited by 737
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Vomund, S., Schäfer, A., Parnham, M., Brüne, B., & Von Knethen, A. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18122772 · Cited by 752
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Vasan, K., Werner, M., & Chandel, N. S. (2020) · Cell Metabolism · doi:10.1016/j.cmet.2020.06.019 · Cited by 762
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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 687
Roesch, A., Vultur, A., Bogeski, I., Wang, H., Zimmermann, K. M., Speicher, D., Körbel, C., Laschke, M. W., Gimotty, P. A., Philipp, S. E., et al. (2013) · Cancer Cell · doi:10.1016/j.ccr.2013.05.003 · Cited by 670
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Zhang, W., Wang, G., Xu, Z., Tu, H.-Q., Hu, F., Dai, J., Chang, Y., Chen, Y., Lu, Y., Zeng, H., et al. (2019) · Cell · doi:10.1016/j.cell.2019.05.003 · Cited by 606
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Reczek, C. R., & Chandel, N. S. (2017) · Annual Review of Cancer Biology · doi:10.1146/annurev-cancerbio-041916-065808 · Cited by 602
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Kimmelman, A. C. (2011) · Genes & Development · doi:10.1101/gad.17558811 · Cited by 599
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Wiel, C., Le Gal, K., Ibrahim, M. X., Jahangir, C. A., Kashif, M., Yao, H., Ziegler, D. V., Xu, X., Ghosh, T., Mondal, T., et al. (2019) · Cell · doi:10.1016/j.cell.2019.06.005 · Cited by 579
The role of nuclear lamin B1 in cell proliferation and senescence
Shimi, T., Butin-Israeli, V., Adam, S. A., Hamanaka, R. B., Goldman, A. E., Lucas, C. A., Shumaker, D. K., Kosak, S. T., Chandel, N. S., & Goldman, R. D. (2011) · Genes & Development · doi:10.1101/gad.179515.111 · Cited by 547
Self-citationA Mitochondrial Switch Promotes Tumor Metastasis
Porporato, P. E., Payen, V. L., Pérez‐Escuredo, J., Saedeleer, C. J. D., Danhier, P., Copetti, T., Dhup, S., Tardy, M., Vazeille, T., Bouzin, C., et al. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.06.043 · Cited by 571
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Park, J. H., Pyun, W. Y., & Park, H. W. (2020) · Cells · doi:10.3390/cells9102308 · Cited by 571
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Chio, I. I. C., & Tuveson, D. A. (2017) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2017.03.004 · Cited by 532
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Luengo, A., Li, Z., Gui, D. Y., Sullivan, L. B., Zagorulya, M., Do, B. T., Ferreira, R., Naamati, A., Ali, A., Lewis, C. A., et al. (2021) · Molecular Cell · doi:10.1016/j.molcel.2020.12.012 · Cited by 547
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Abate, M., Festa, A., Falco, M., Lombardi, A., Luce, A., Grimaldi, A., Zappavigna, S., Sperlongano, P., Irace, C., Caraglia, M., et al. (2019) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2019.05.022 · Cited by 552
Duch, M. C., Budinger, G. R. S., Liang, Y. T., Soberanes, S., Urich, D., Chiarella, S. E., Campochiaro, L. A., Gonzalez, A., Chandel, N. S., Hersam, M. C., et al. (2011) · Nano Letters · doi:10.1021/nl202515a · Cited by 552
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Manz, D. H., Blanchette, N. L., Paul, B. T., Torti, F. M., & Torti, S. V. (2016) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.13008 · Cited by 507
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Cheresh, P., Kim, S.-J., Tulasiram, S., & Kamp, D. W. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2012.11.021 · Cited by 534
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Metadata
- Authors
- 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.
- Affiliations
- Northwestern University (US)
- Division of Pulmonary and Critical Care, Department of Medicine,
- Medical College of Wisconsin (US)
- Department of Biophysics and Free Radical Research Center, Medical College of Wisconsin, Milwaukee, WI 53226
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2010-04-26
- Volume
- 107
- Issue
- 19
- Pages
- 8788-8793
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2889315
- OpenAlex
- W1982330633
- Cited by
- 1,742
- References
- 29
- Citations by year
- 2026: 63 · 2025: 100 · 2024: 124 · 2023: 122 · 2022: 149 · 2021: 154 · 2020: 137 · 2019: 138 · 2018: 111 · 2017: 108 · 2016: 100 · 2015: 113 · 2014: 89 · 2013: 77 · 2012: 77
- FWCI
- 23.58
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Veterans Affairs (I01 BX000201)
- LUNGevity Foundation
- Respiratory Health Association of Metropolitan Chicago
- Respiratory Health Association
- National Institutes of Health
- National Heart, Lung, and Blood Institute (P01HL071643)
- National Cancer Institute (R01CA125112, R01CA152810, R01CA123067, CA125112, P30CA060553, T32CA070085, T32CA009560)
- National Institute of Environmental Health Sciences (ES 013995, ES015024, R01ES013995, R01ES015024)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- KRAS, mitochondrial metabolism, reactive oxygen species, pentose phosphate pathway, aerobic glycolysis, Warburg effect, anchorage-independent growth, glutaminase, alpha-ketoglutarate, TCA cycle, ERK signaling, mitochondrial complex III, TFAM, lung cancer, carcinogenesis, hypoxia
- MeSH terms
- Aerobiosis, Animals, Cell Adhesion, Cell Transformation, Neoplastic, Glutamine, Glycolysis, Humans, Lung Neoplasms, Mitochondria, Oxidative Phosphorylation, Pentose Phosphate Pathway, Electron Transport Complex III, Proto-Oncogene Proteins p21(ras), Reactive Oxygen Species, HCT116 Cells, Extracellular Signal-Regulated MAP Kinases, Cell Proliferation, Mice
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