Oxidative stress inhibits distant metastasis by human melanoma cells
Open accessAbstract
Solid cancer cells commonly enter the blood and disseminate systemically, but are highly inefficient at forming distant metastases for poorly understood reasons. Here we studied human melanomas that differed in their metastasis histories in patients and in their capacity to metastasize in NOD-SCID-Il2rg(-/-) (NSG) mice. We show that melanomas had high frequencies of cells that formed subcutaneous tumours, but much lower percentages of cells that formed tumours after intravenous or intrasplenic transplantation, particularly among inefficiently metastasizing melanomas. Melanoma cells in the blood and visceral organs experienced oxidative stress not observed in established subcutaneous tumours. Successfully metastasizing melanomas underwent reversible metabolic changes during metastasis that increased their capacity to withstand oxidative stress, including increased dependence on NADPH-generating enzymes in the folate pathway. Antioxidants promoted distant metastasis in NSG mice. Folate pathway inhibition using low-dose methotrexate, ALDH1L2 knockdown, or MTHFD1 knockdown inhibited distant metastasis without significantly affecting the growth of subcutaneous tumours in the same mice. Oxidative stress thus limits distant metastasis by melanoma cells in vivo.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Emerging work suggests that increased serine synthesis may be particularly important for maintaining redox homeostasis during metastasis.
“Emerging work suggests that increased serine synthesis may be particularly important for maintaining redox homeostasis during metastasis (Piskounova et al., 2015).”
From Targeting Metabolism for Cancer Therapy (2017) · cites this paper as Piskounova et al., 2015
Antioxidants including N-acetyl l-cysteine (NAC) and vitamin E markedly increased tumor progression and cancer metastasis.
“However, in reality, previous studies have demonstrated that antioxidants, including N‐acetyl l‐cysteine (NAC) and vitamin E, markedly increased tumor progression and cancer metastasis.10, 11”
From Reactive Oxygen Species in Cancer: Current Findings and Future Directions (2021) · cites this paper as [11]
Human and animal studies have not clearly shown that antioxidants prevent or suppress cancer.
“recent results from both human and animal studies have found no clear evidence of the benefit of antioxidant treatment in preventing or suppressing cancer development.”
From Targeting cancer vulnerabilities with high-dose vitamin C (2019) · cites this paper as [16]
In mouse models of lung adenocarcinoma and melanoma, antioxidants seemed to speed cancer progression and metastasis.
“antioxidant treatment even appeared to accelerate cancer progression and metastasis in mouse models of lung adenocarcinoma and melanoma14–16”
From Targeting cancer vulnerabilities with high-dose vitamin C (2019) · cites this paper as [16]
Antioxidant supplementation of the diet accelerates tumor progression in immunodeficient mice with implanted patients' lung cancer or malignant melanoma cells.
“Antioxidant supplementation of the diet has been found to accelerate tumor progression in immunodeficient mice with implanted patients’ lung cancer or malignant melanoma cells (Piskounova et al. 2015).”
From Reactive Oxygen Species, Toxicity, Oxidative Stress, and Antioxidants: Chronic Diseases and Aging (2023) · cites this paper as Piskounova et al. 2015
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
(1994) · New England Journal of Medicine · doi:10.1056/nejm199404143301501 · Cited by 4,737 · see citing works
Modulation of oxidative stress as an anticancer strategy
Gorrini, C., Harris, I. S., & Mak, T. W. (2013) · Nature Reviews Drug Discovery · doi:10.1038/nrd4002 · Cited by 3,579 · see citing works
Isolation of rare circulating tumour cells in cancer patients by microchip technology
Nagrath, S., Sequist, L. V. D., Maheswaran, S., Bell, D. W., Irimia, D., Ulkus, L., Smith, M. R., Kwak, E. L., Digumarthy, S. R., Muzikansky, A., et al. (2007) · Nature · doi:10.1038/nature06385 · Cited by 3,565 · see citing works
Circulating Breast Tumor Cells Exhibit Dynamic Changes in Epithelial and Mesenchymal Composition
Yu, M., Bardia, A., Wittner, B. S., Stott, S. L., Smas, M. E., Ting, D. T., Isakoff, S. J., Ciciliano, J. C., Wells, M. N., Shah, A. M., et al. (2013) · Science · doi:10.1126/science.1228522 · Cited by 2,476 · see citing works
Oncogene-induced Nrf2 transcription promotes ROS detoxification and tumorigenesis
DeNicola, G. M., Karreth, F. A., Humpton, T. J., Gopinathan, A., Wei, C., Frese, K., Mangal, D., Yu, K. H., Yeo, C. J., Calhoun, E. S., et al. (2011) · Nature · doi:10.1038/nature10189 · Cited by 2,277 · see citing works
Hu, Y., & Smyth, G. K. (2009) · Journal of Immunological Methods · doi:10.1016/j.jim.2009.06.008 · Cited by 2,091 · see citing works
Klein, E. A., Thompson, I. M., Tangen, C. M., Crowley, J. J., Lucia, M. S., Goodman, P. J., Minasian, L. M., Ford, L. G., Parnes, H. L., Gaziano, J. M., et al. (2011) · JAMA · doi:10.1001/jama.2011.1437 · Cited by 1,787 · see citing works
Functional genomics reveal that the serine synthesis pathway is essential in breast cancer
Possemato, R., Marks, K. M., Shaul, Y. D., Pacold, M. E., Kim, D., Birsoy, K., Sethumadhavan, S., Woo, H.-K., Jang, H. G., Jha, A. K., et al. (2011) · Nature · doi:10.1038/nature10350 · Cited by 1,683 · see citing works
ROS-Generating Mitochondrial DNA Mutations Can Regulate Tumor Cell Metastasis
Ishikawa, K., Takenaga, K., Akimoto, M., Koshikawa, N., Yamaguchi, A., Imanishi, H., Nakada, K., Honma, Y., & Hayashi, J.-I. (2008) · Science · doi:10.1126/science.1156906 · Cited by 1,444 · see citing works
LeBleu, V. S., O’Connell, J. T., Herrera, K. N. G., Wikman, H., Pantel, K., Haigis, M. C., de Carvalho, F. M., Damascena, A. S., Chinen, L. T. D., Rocha, R. M., et al. (2014) · Nature Cell Biology · doi:10.1038/ncb3039 · Cited by 1,412 · see citing works
Multistep Nature of Metastatic Inefficiency
Luzzi, K. J., MacDonald, I. C., Schmidt, E. E., Kerkvliet, N. I., Morris, V. L., Chambers, A. F., & Groom, A. C. (1998) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)65628-3 · Cited by 1,246 · see citing works
MetaboAnalyst 2.0--a comprehensive server for metabolomic data analysis
Xia, J., Mandal, R., Sinelnikov, I., Broadhurst, D., & Wishart, D. S. (2012) · Nucleic Acids Research · doi:10.1093/nar/gks374 · Cited by 1,146 · see citing works
Real-time imaging reveals the single steps of brain metastasis formation.
Kienast, Y., von Baumgarten, L., Fuhrmann, M., Klinkert, W. E. F., Goldbrunner, R., Herms, J., & Winkler, F. (2010) · Nature Medicine · doi:10.1038/nm.2072 · Cited by 1,138 · see citing works
Phosphoglycerate dehydrogenase diverts glycolytic flux and contributes to oncogenesis
Locasale, J. W., Grassian, A. R., Melman, T., Lyssiotis, C. A., Mattaini, K. R., Bass, A. J., Heffron, G., Metallo, C. M., Muranen, T., Sharfi, H., et al. (2011) · Nature Genetics · doi:10.1038/ng.890 · Cited by 1,120 · see citing works
Quantitative flux analysis reveals folate-dependent NADPH production
Fan, J., Ye, J., Kamphorst, J. J., Shlomi, T., Thompson, C. B., & Rabinowitz, J. D. (2014) · Nature · doi:10.1038/nature13236 · Cited by 1,114 · see citing works
Antioxidant and oncogene rescue of metabolic defects caused by loss of matrix attachment
Schafer, Z. T., Grassian, A. R., Song, L., Jiang, Z., Gerhart-Hines, Z., Irie, H. Y., Gao, S., Puigserver, P., & Brugge, J. S. (2009) · Nature · doi:10.1038/nature08268 · Cited by 1,031 · see citing works
Modelling glandular epithelial cancers in three-dimensional cultures
Debnath, J., & Brugge, J. S. (2005) · Nature reviews. Cancer · doi:10.1038/nrc1695 · Cited by 1,014 · see citing works
Harris, I. S., Treloar, A. E., Inoue, S., Sasaki, M., Gorrini, C., Lee, K. C., Yung, K. Y., Brenner, D., Knobbe-Thomsen, C. B., Cox, M. A., et al. (2015) · Cancer Cell · doi:10.1016/j.ccell.2014.11.019 · Cited by 993 · see citing works
Ex vivo culture of circulating breast tumor cells for individualized testing of drug susceptibility
Yu, M., Bardia, A., Aceto, N., Bersani, F., Madden, M. W., Collier, M. D., Desai, R. N., Zhu, H., Comaills, V., Zheng, Z., et al. (2014) · Science · doi:10.1126/science.1253533 · Cited by 915 · see citing works
Antioxidants Accelerate Lung Cancer Progression in Mice
Sayin, V. I., Ibrahim, M. X., Larsson, E., Nilsson, J. A., Lindahl, P., & Bergo, M. O. (2014) · Science Translational Medicine · doi:10.1126/scitranslmed.3007653 · Cited by 867 · see citing works
Loss of FBP1 by Snail-Mediated Repression Provides Metabolic Advantages in Basal-like Breast Cancer
Dong, C., Yuan, T., Wu, Y., Wang, Y., Fan, T. W. ‐., Miriyala, S., Lin, Y., Yao, J., Shi, J., Kang, T., et al. (2013) · Cancer Cell · doi:10.1016/j.ccr.2013.01.022 · Cited by 806 · see citing works
Debnath, J., Mills, K. R., Collins, N. L., Reginato, M. J., Muthuswamy, S. K., & Brugge, J. S. (2002) · Cell · doi:10.1016/s0092-8674(02)01001-2 · Cited by 763 · see citing works
A 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 · see citing works
Vanharanta, S., & Massagué, J. (2013) · Cancer Cell · doi:10.1016/j.ccr.2013.09.007 · Cited by 563 · 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
Stott, S. L., Lee, R. J., Nagrath, S., Yu, M., Miyamoto, D. T., Ulkus, L., Inserra, E. K., Ulman, M. J., Springer, S. U., Nakamura, Z. M., et al. (2010) · Science Translational Medicine · doi:10.1126/scitranslmed.3000403 · Cited by 540 · 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
Targeting antioxidants for cancer therapy
Glasauer, A., & Chandel, N. S. (2014) · Biochemical Pharmacology · doi:10.1016/j.bcp.2014.07.017 · Cited by 502 · see citing works
Reciprocal regulation of p53 and malic enzymes modulates metabolism and senescence
Jiang, P., Du, W., Mancuso, A., Wellen, K. E., & Yang, X. (2013) · Nature · doi:10.1038/nature11776 · Cited by 491 · see citing works
Serine Catabolism Regulates Mitochondrial Redox Control during Hypoxia
Ye, J., Fan, J., Venneti, S., Wan, Y.-W., Pawel, B. R., Zhang, J., Finley, L. W. S., Lu, C., Lindsten, T., Cross, J. R., et al. (2014) · Cancer Discovery · doi:10.1158/2159-8290.cd-14-0250 · Cited by 452 · see citing works
Fortmann, S. P., Burda, B. U., Senger, C. A., Lin, J. S., & Whitlock, E. P. (2013) · Annals of Internal Medicine · doi:10.7326/0003-4819-159-12-201312170-00729 · Cited by 442 · see citing works
Goodman, G. E., Thornquist, M. D., Balmes, J. R., Cullen, M. R., Meyskens, F. L., Omenn, G. S., VALANIS, B. G., & Williams, J. H. (2004) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djh320 · Cited by 430 · see citing works
Cancer Incidence and Mortality After Treatment With Folic Acid and Vitamin B12
Ebbing, M. (2009) · JAMA · doi:10.1001/jama.2009.1622 · Cited by 428 · see citing works
Cameron, M. D., Schmidt, E. E., Kerkvliet, N. I., Nadkarni, K. V., Morris, V. L., Groom, A. C., Chambers, A. F., & MacDonald, I. C. (2000) · PubMed · Cited by 400 · see citing works
Adaptation of Energy Metabolism in Breast Cancer Brain Metastases
Chen, E. I., Hewel, J. A., Krueger, J. S., Tiraby, C., Weber, M. R., Kralli, A., Becker, K., Yates, J. R., & Felding‐Habermann, B. (2007) · Cancer Research · doi:10.1158/0008-5472.can-06-3137 · Cited by 353 · see citing works
Mullen, A. R., Hu, Z., Shi, X., Jiang, L., Boroughs, L. K., Kovacs, Z., Boriack, R., Rakheja, D., Sullivan, L. B., Linehan, W. M., et al. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.04.037 · Cited by 337 · see citing works
Self-citationATF4-dependent induction of heme oxygenase 1 prevents anoikis and promotes metastasis
Dey, S., Sayers, C. M., Verginadis, I. I., Lehman, S. L., Cheng, Y., Cerniglia, G. J., Tuttle, S. W., Feldman, M. D., Zhang, P. J. L., Fuchs, S. Y., et al. (2015) · Journal of Clinical Investigation · doi:10.1172/jci78031 · Cited by 282 · see citing works
Cyclic changes in metabolic state during the life of a yeast cell
Tu, B. P., Mohler, R. E., Liu, J. C., Dombek, K. M., Young, E. T., Synovec, R. E., & McKnight, S. L. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0708365104 · Cited by 260 · see citing works
Targeting SOD1 reduces experimental non–small-cell lung cancer
Glasauer, A., Sena, L. A., Diebold, L. P., Mazar, A. P., & Chandel, N. S. (2013) · Journal of Clinical Investigation · doi:10.1172/jci71714 · Cited by 212 · see citing works
The Promise and Perils of Antioxidants for Cancer Patients
Chandel, N. S., & Tuveson, D. A. (2014) · New England Journal of Medicine · doi:10.1056/nejmcibr1405701 · Cited by 207 · see citing works
The significance of the circulating cancer cell
Salsbury, A. J. (1975) · Cancer Treatment Reviews · doi:10.1016/s0305-7372(75)80015-6 · Cited by 198 · see citing works
Engell, H. C. (1959) · Annals of Surgery · doi:10.1097/00000658-195904000-00001 · Cited by 142 · see citing works
Manganese superoxide dismutase promotes anoikis resistance and tumor metastasis
Kamarajugadda, S., Cai, Q., Chen, H., Nayak, S., Zhu, J., He, M., Jin, Y., Zhang, Y., Ai, L., Martin, S. S., et al. (2013) · Cell Death and Disease · doi:10.1038/cddis.2013.20 · Cited by 139 · see citing works
Qu, Y., Wang, J., Ray, P., Guo, H. B., Huang, J., Shin-Sim, M., Bukoye, B. A., Liu, B., Lee, A. V., Lin, X., et al. (2010) · Journal of Clinical Investigation · doi:10.1172/jci43144 · Cited by 126 · see citing works
Human Melanoma Metastasis in NSG Mice Correlates with Clinical Outcome in Patients
Quintana, E., Piskounova, E., Shackleton, M. J., Weinberg, D. N., Eskiocak, U., Fullen, D. R., Johnson, T. M., & Morrison, S. J. (2012) · Science Translational Medicine · doi:10.1126/scitranslmed.3004599 · Cited by 108 · see citing works
Self-citationLü, X., Bennet, B., Mu, E. W., Rabinowitz, J. D., & Kang, Y. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.c110.104448 · Cited by 104 · see citing works
Teoh-Fitzgerald, M. L. T., Fitzgerald, M. P., Zhong, W., et al. (2013) · Oncogene · doi:10.1038/onc.2012.582 · Cited by 92 · see citing works
Folic Acid Supplementation Promotes Mammary Tumor Progression in a Rat Model
Manshadi, S. D., Ishiguro, L., Sohn, K., Medline, A., Renlund, R., Croxford, R., & Kim, Y. (2014) · PLoS ONE · doi:10.1371/journal.pone.0084635 · Cited by 90 · see citing works
Scheinin, T. M., & Koivuniemi, A. (1959) · The Lancet · doi:10.1016/s0140-6736(59)90062-5 · Cited by 32 · see citing works
Fortmann, S. P., Burda, B. U., Senger, C. A., Lin, J. S., Beil, T. L., O’Connor, E., & Whitlock, E. P. (2013) · Cited by 30 · see citing works
Studies on the acid mucopolysaccharide coat of viruses and transformed cells
Shigematsu, T., & Dmochowski, L. L. (1973) · Cancer · doi:10.1002/1097-0142(197301)31:1 · Cited by 23 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
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
Self-citationMetabolic reprogramming and cancer progression
Faubert, B., Solmonson, A., & DeBerardinis, R. J. (2020) · Science · doi:10.1126/science.aaw5473 · Cited by 2,740 · see citing works
Self-citationHayes, J. D., Dinkova-Kostova, A. T., & Tew, K. D. (2020) · Cancer Cell · doi:10.1016/j.ccell.2020.06.001 · Cited by 2,654 · see citing works
Reactive 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 · see citing works
One-Carbon Metabolism in Health and Disease
Ducker, G. S., & Rabinowitz, J. D. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2016.08.009 · Cited by 2,239 · see citing works
Metastatic colonization by circulating tumour cells
Massagué, J., & Obenauf, A. C. (2016) · Nature · doi:10.1038/nature17038 · Cited by 2,062 · see citing works
Vyas, S., Zaganjor, E., & Haigis, M. C. (2016) · Cell · doi:10.1016/j.cell.2016.07.002 · Cited by 1,735 · 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
Endoplasmic reticulum stress signals in the tumour and its microenvironment
Chen, X., & Cubillos-Ruiz, J. R. (2021) · Nature Reviews Cancer · doi:10.1038/s41568-020-00312-2 · Cited by 1,356 · see citing works
Reactive Oxygen Species in Cancer: Current Findings and Future Directions
Nakamura, H., & Takada, K. (2021) · Cancer Science · doi:10.1111/cas.15068 · Cited by 1,027 · see citing works
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 · see citing works
Serine and one-carbon metabolism in cancer
Yang, M., & Vousden, K. H. (2016) · Nature Reviews Cancer · doi:10.1038/nrc.2016.81 · Cited by 992 · see citing works
Role of Glutathione in Cancer: From Mechanisms to Therapies
Kennedy, L., Sandhu, J. K., Harper, M.-E., & Cuperlovic-Culf, M. (2020) · Biomolecules · doi:10.3390/biom10101429 · Cited by 880 · see citing works
The role of cellular reactive oxygen species in cancer chemotherapy
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 · see citing works
ROS signaling under metabolic stress: cross-talk between AMPK and AKT pathway
Zhao, Y., Hu, X., Liu, Y., Dong, S., Wen, Z., He, W., Zhang, S., Huang, Q., & Shi, M. (2017) · Molecular Cancer · doi:10.1186/s12943-017-0648-1 · Cited by 735 · see citing works
Mechanisms and Implications of Metabolic Heterogeneity in Cancer
Kim, J., & DeBerardinis, R. J. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.08.013 · Cited by 606 · see citing works
Self-citationReductive 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-citationThe Two Faces of Reactive Oxygen Species in Cancer
Reczek, C. R., & Chandel, N. S. (2017) · Annual Review of Cancer Biology · doi:10.1146/annurev-cancerbio-041916-065808 · Cited by 602 · see citing works
“Furthermore, human melanoma cells require the NADPH-generating enzymes of the folate-mediated one-carbon metabolism pathway to promote distant metastasis (Piskounova et al. 2015).”
BackgroundInfluentialBACH1 Stabilization by Antioxidants Stimulates Lung Cancer Metastasis
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 · see citing works
ROS in Cancer: The Burning Question
Chio, I. I. C., & Tuveson, D. A. (2017) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2017.03.004 · Cited by 532 · see citing works
Metabolic heterogeneity confers differences in melanoma metastatic potential
Tasdogan, A., Faubert, B., Ramesh, V., Ubellacker, J. M., Shen, B., Solmonson, A., Murphy, M. M., Gu, Z., Gu, W., Martin, M., et al. (2020) · Nature · doi:10.1038/s41586-019-1847-2 · Cited by 509 · see citing works
Self-citationPeiris-Pagès, M., Martinez-Outschoorn, U. E., Pestell, R. G., Sotgia, F., & Lisanti, M. P. (2016) · Breast Cancer Research · doi:10.1186/s13058-016-0712-6 · Cited by 465 · see citing works
The multifaceted role of reactive oxygen species in tumorigenesis
Kirtonia, A., Sethi, G., & Garg, M. (2020) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-020-03536-5 · Cited by 452 · see citing works
Reversal of cytosolic one-carbon flux compensates for loss of the mitochondrial folate pathway
Ducker, G. S., Chen, L., Morscher, R. J., Ghergurovich, J. M., Esposito, M., Teng, X., Kang, Y., & Rabinowitz, J. D. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.04.016 · Cited by 419 · see citing works
RETRACTED: Therapeutic potential of flavonoids in cancer: ROS-mediated mechanisms
Slika, H., Mansour, H., Wehbe, N., Nasser, S. A., Iratni, R., Nasrallah, G., Shaito, A., Ghaddar, T., Kobeissy, F., & Eid, A. H. (2022) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2021.112442 · Cited by 441 · see citing works
RetractedMitochondrial Biogenesis and Proteome Remodeling Promote One-Carbon Metabolism for T Cell Activation
Ron-Harel, N., Santos, D., Ghergurovich, J. M., Sage, P. T., Reddy, A., Lovitch, S. B., Dephoure, N., Satterstrom, F. K., Sheffer, M., Spinelli, J. B., et al. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.06.007 · Cited by 429 · see citing works
Targeting cancer vulnerabilities with high-dose vitamin C
Ngo, B., Van Riper, J. M., Cantley, L. C., & Yun, J. (2019) · Nature Reviews Cancer · doi:10.1038/s41568-019-0135-7 · Cited by 423 · see citing works
Metastasis-Initiating Cells and Ecosystems
Massagué, J., & Ganesh, K. (2021) · Cancer Discovery · doi:10.1158/2159-8290.cd-21-0010 · Cited by 372 · see citing works
Targeting iron metabolism in drug discovery and delivery
Crielaard, B. J., Lammers, T., & Rivella, S. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2016.248 · Cited by 352 · see citing works
Compensatory metabolic networks in pancreatic cancers upon perturbation of glutamine metabolism
Biancur, D. E., Paulo, J. A., Małachowska, B., Quiles Del Rey, M., Sousa, C. M., Wang, X., Sohn, A. S. W., Chu, G. C., Gygi, S. P., Harper, J. W., et al. (2017) · Nature Communications · doi:10.1038/ncomms15965 · Cited by 315 · see citing works
Slow TCA flux and ATP production in primary solid tumours but not metastases
Bartman, C. R., Weilandt, D. R., Shen, Y., Lee, W. D., Han, Y., TeSlaa, T., Jankowski, C. S. R., Samarah, L., Park, N. R., da Silva-Diz, V., et al. (2023) · Nature · doi:10.1038/s41586-022-05661-6 · Cited by 299 · see citing works
Self-citationSayin, V. I., LeBoeuf, S. E., Singh, S. X., Davidson, S. M., Biancur, D., Guzelhan, B. S., Alvarez, S. W., Wu, W. L., Karakousi, T. R., Zavitsanou, A. M., et al. (2017) · eLife · doi:10.7554/elife.28083 · Cited by 231 · see citing works
Applications of metabolomics to study cancer metabolism
Kaushik, A. K., & DeBerardinis, R. J. (2018) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2018.04.009 · Cited by 179 · see citing works
Self-citationOxidative guanine base damage regulates human telomerase activity
Fouquerel, E., Lormand, J., Bose, A., Lee, H.-T., Kim, G. S., Li, J., Sobol, R. W., Freudenthal, B. D., Myong, S., & Opresko, P. L. (2016) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.3319 · Cited by 182 · see citing works
Impact of oxidative stress on telomere biology
Ahmed, W., & Lingner, J. (2018) · Differentiation · doi:10.1016/j.diff.2017.12.002 · Cited by 153 · see citing works
Maintenance of redox homeostasis by hypoxia-inducible factors
Samanta, D., & Semenza, G. L. (2017) · Redox Biology · doi:10.1016/j.redox.2017.05.022 · Cited by 127 · see citing works
Emanuelli, M., Sartini, D., Molinelli, E., Campagna, R., Pozzi, V., Salvolini, E., Simonetti, O., Campanati, A., & Offidani, A. (2022) · Antioxidants · doi:10.3390/antiox11040612 · Cited by 132 · see citing works
Roberts, R. D., Lizardo, M. M., Reed, D. R., Hingorani, P., Glover, J., Allen‐Rhoades, W., Fan, T., Khanna, C., Sweet‐Cordero, E. A., Cash, T., et al. (2019) · Cancer · doi:10.1002/cncr.32351 · Cited by 127 · see citing works
Reprogramming of serine, glycine and one-carbon metabolism in cancer
Li, A. M., & Ye, J. (2020) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2020.165841 · Cited by 127 · see citing works
Oxidative stress and antioxidants in the pathophysiology of malignant melanoma
Obrador, E., Liu-Smith, F., Dellinger, R. W., Salvador, R., Meyskens, F. L., & Estrela, J. M. (2019) · Biological Chemistry · doi:10.1515/hsz-2018-0327 · Cited by 119 · see citing works
Zaytseva, Y. Y., Rychahou, P. G., Le, A.-T., Scott, T. L., Flight, R. M., Kim, J. T., Harris, J., Liu, J., Wang, C., Morris, A. J., et al. (2018) · Oncotarget · doi:10.18632/oncotarget.25361 · Cited by 123 · see citing works
Fan, T. M., Roberts, R. D., & Lizardo, M. M. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.00013 · Cited by 90 · see citing works
De Angelis, M. L., Francescangeli, F., Nicolazzo, C., Signore, M., Giuliani, A., Colace, L., Boe, A., Magri, V., Baiocchi, M., Ciardi, A., et al. (2022) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-022-02263-y · Cited by 75 · see citing works
The Oxygen Paradox, the French Paradox, and age-related diseases
Davies, J. M. S., Cillard, J., Friguet, B., Cadenas, E., Cadet, J., Cayce, R., Fishmann, A., Liao, D., Bulteau, A.-L., Derbré, F., et al. (2017) · GeroScience · doi:10.1007/s11357-017-0002-y · Cited by 82 · see citing works
Oxidative Stress-Related Mechanisms in Melanoma and in the Acquired Resistance to Targeted Therapies
Pizzimenti, S., Ribero, S., Cucci, M. A., Grattarola, M., Monge, C., Dianzani, C., Barrera, G., & Muzio, G. (2021) · Antioxidants · doi:10.3390/antiox10121942 · Cited by 79 · see citing works
Metabolism during ECM Detachment: Achilles Heel of Cancer Cells?
Mason, J. A., Hagel, K. R., Hawk, M. A., & Schafer, Z. T. (2017) · Trends in Cancer · doi:10.1016/j.trecan.2017.04.009 · Cited by 78 · see citing works
Varum, S., Baggiolini, A., Zurkirchen, L., Atak, Z. K., Cantù, C., Marzorati, E., Bossart, R., Wouters, J., Häusel, J., Tuncer, E., et al. (2019) · Cell Stem Cell · doi:10.1016/j.stem.2019.03.011 · Cited by 65 · see citing works
STIM-Orai Channels and Reactive Oxygen Species in the Tumor Microenvironment
Frisch, J., Angenendt, A., Hoth, M., Prates Roma, L., & Lis, A. (2019) · Cancers · doi:10.3390/cancers11040457 · Cited by 68 · see citing works
Wan, X., Wang, C., Huang, Z., Zhou, D., Xiang, S., Qi, Q., Chen, X., Arbely, E., Liu, C.-Y., Du, P., et al. (2020) · Cell Death & Disease · doi:10.1038/s41419-020-02825-y · Cited by 60 · see citing works
Noguchi, K., Konno, M., Koseki, J., Nishida, N., Kawamoto, K., Yamada, D., Asaoka, T., Noda, T., Wada, H., Gotoh, K., et al. (2018) · Oncology Letters · doi:10.3892/ol.2018.8795 · Cited by 60 · see citing works
Dorsch, M., Kowalczyk, M., Planque, M., Heilmann, G., Urban, S., Dujardin, P., Forster, J., Ueffing, K., Nothdurft, S., Oeck, S., et al. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.110056 · Cited by 55 · see citing works
Inflammatory response and oxidative stress during liver resection
Schwarz, C., Fitschek, F., Bar-Or, D., Klaus, D. A., Tudor, B., Fleischmann, E., Roth, G., Tamandl, D., Wekerle, T., Gnant, M., et al. (2017) · PLOS ONE · doi:10.1371/journal.pone.0185685 · Cited by 47 · see citing works
Zhang, H., Zhu, S., Zhou, H., Li, R., Xia, X., & Xiong, H. (2023) · Frontiers in Oncology · doi:10.3389/fonc.2023.1098357 · Cited by 46 · see citing works
Metabolic reprogramming: a bridge between aging and tumorigenesis
Drapela, S., Ilter, D., & Gomes, A. P. (2022) · Molecular Oncology · doi:10.1002/1878-0261.13261 · Cited by 41 · see citing works
Bechard, M. E., Smalling, R., Hayashi, A., Zhong, Y., Word, A. E., Campbell, S. L., Tran, A. V., Weiss, V. L., Iacobuzio-Donahue, C., Wellen, K. E., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-17839-5 · Cited by 33 · see citing works
Freund, E., Miebach, L., Stope, M., & Bekeschus, S. (2021) · Oncology Reports · doi:10.3892/or.2021.8022 · Cited by 18 · see citing works
- Authors
- Piskounova, E., Agathocleous, M., Murphy, M. M., Hu, Z., Huddlestun, S. E., Zhao, Z., Leitch, A. M., Johnson, T. M., DeBerardinis, R. J., & Morrison, S. J.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- University of Michigan (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Morrison, Sean J.
- ORCID
- Venue
- Nature
- Published
- 2015-10-14
- Volume
- 527
- Issue
- 7577
- Pages
- 186-191
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC4644103
- OpenAlex
- W2098131661
- Cited by
- 1,269
- References
- 51
- Citations by year
- 2026: 82 · 2025: 107 · 2024: 108 · 2023: 109 · 2022: 155 · 2021: 141 · 2020: 151 · 2019: 113 · 2018: 96 · 2017: 107 · 2016: 93 · 2015: 5
- FWCI
- 43.51
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- National Cancer Institute (K99CA201228, P30CA142543)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Keywords
- melanoma, distant metastasis, oxidative stress, folate pathway, NADPH metabolism, MTHFD1, ALDH1L2, methotrexate, antioxidants, cancer metabolism, NSG mice
- MeSH terms
- Formyltetrahydrofolate Dehydrogenase, Oxidoreductases Acting on CH-NH Group Donors, Animals, Antioxidants, Female, Folic Acid, Humans, Male, Melanoma, Methotrexate, Methylenetetrahydrofolate Dehydrogenase (NADP), NADP, Neoplasm Metastasis, Neoplasm Transplantation, Minor Histocompatibility Antigens, Mice, SCID, Mice, Inbred NOD, Oxidative Stress, Mice, Gene Knockdown Techniques
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
