Cited by 500Cancer, Hypoxia, and MetabolismMetabolism, Diabetes, and CancerCancer, Lipids, and Metabolism

The DOI matches its Crossref record; 44 of the 44 references it cites were found in a registry or an index.

Pyruvate carboxylase is critical for non–small-cell lung cancer proliferation

Open access

Sellers, Katherine, Fox, Matthew P., Bousamra, Michael, Slone, Stephen P., Higashi, Richard M., Miller, Donald M., Wang, Yali, Yan, Jun, Yuneva, Mariia O., Deshpande, Rahul, Lane, Andrew N., Fan, Teresa W.-M.·2015·Journal of Clinical Investigation

DOI 10.1172/jci72873PMC PMC4319441

Open this paper in CoChat — free account

Abstract

Anabolic biosynthesis requires precursors supplied by the Krebs cycle, which in turn requires anaplerosis to replenish precursor intermediates. The major anaplerotic sources are pyruvate and glutamine, which require the activity of pyruvate carboxylase (PC) and glutaminase 1 (GLS1), respectively. Due to their rapid proliferation, cancer cells have increased anabolic and energy demands; however, different cancer cell types exhibit differential requirements for PC- and GLS-mediated pathways for anaplerosis and cell proliferation. Here, we infused patients with early-stage non-small-cell lung cancer (NSCLC) with uniformly 13C-labeled glucose before tissue resection and determined that the cancerous tissues in these patients had enhanced PC activity. Freshly resected paired lung tissue slices cultured in 13C6-glucose or 13C5,15N2-glutamine tracers confirmed selective activation of PC over GLS in NSCLC. Compared with noncancerous tissues, PC expression was greatly enhanced in cancerous tissues, whereas GLS1 expression showed no trend. Moreover, immunohistochemical analysis of paired lung tissues showed PC overexpression in cancer cells rather than in stromal cells of tumor tissues. PC knockdown induced multinucleation, decreased cell proliferation and colony formation in human NSCLC cells, and reduced tumor growth in a mouse xenograft model. Growth inhibition was accompanied by perturbed Krebs cycle activity, inhibition of lipid and nucleotide biosynthesis, and altered glutathione homeostasis. These findings indicate that PC-mediated anaplerosis in early-stage NSCLC is required for tumor survival and proliferation.

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

Crossref · 10.1172/jci72873

Cites

44 of 44 references verified0 citation errors · 0 not checkable

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?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Hallmarks of Cancer: The Next Generation
Hanahan, D., & Weinberg, R. A. (2011) · Cell · doi:10.1016/j.cell.2011.02.013 · Cited by 66,590
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
On the origin of cancer cells
Warburg, O. (1956) · Science · doi:10.1126/science.123.3191.309 · Cited by 13,425
Fundamentals of Biostatistics.
(1969) · Annals of Internal Medicine · doi:10.7326/0003-4819-70-4-873 · Cited by 4,573
Beyond aerobic glycolysis: transformed cells can engage in glutamine metabolism that exceeds the requirement for protein and nucleotide synthesis
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
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
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
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
Oncogenic alterations of metabolism
Dang, C. V., & Semenza, G. L. (1999) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(98)01344-9 · Cited by 1,106
Glucose-Independent Glutamine Metabolism via TCA Cycling for Proliferation and Survival in B Cells
Le, A., Lane, A. N., Hamaker, M., Bose, S., Gouw, A., Barbi, J., Tsukamoto, T., Rojas, C. J., Slusher, B. S., Zhang, H., et al. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2011.12.009 · Cited by 1,095
Self-citation

Flagged first, then by citations

Show all 44 references

Research works printed but not linked: 6

Serkova, 2007, Curr Opin Mol Ther., 9, 572
Mazurek, 2000, Anticancer Res., 20, 5151
Warburg, 1923, Biochem Zeitschr., 142, 317
Mazurek, 2003, Anticancer Res., 23, 1149
Lobo, 2000, Biochem J., 348, 257, 10.1042/0264-6021:3480257 · DOI · Paper page
10.1016/j.cmet.2012.05.001 · DOI · Paper page

Sorted by citations

Items 101–200 of 500

Translational and HIF-1α-Dependent Metabolic Reprogramming Underpin Metabolic Plasticity and Responses to Kinase Inhibitors and Biguanides
Hulea, L., Gravel, S., Morita, M., Cargnello, M., Uchenunu, O., Im, Y. K., Lehuédé, C., Ma, E. H., Leibovitch, M., McLaughlan, S., et al. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.09.001 · Cited by 91
Understanding metabolism with flux analysis: From theory to application
Dai, Z., & Locasale, J. W. (2016) · Metabolic Engineering · doi:10.1016/j.ymben.2016.09.005 · Cited by 92
Metabolism in the Tumor Microenvironment
Lau, A. N., & Heiden, M. G. V. (2019) · Annual Review of Cancer Biology · doi:10.1146/annurev-cancerbio-030419-033333 · Cited by 92
Glutamine as an Essential Amino Acid for KRas-Driven Cancer Cells
Bernfeld, E., & Foster, D. A. (2019) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2019.03.003 · Cited by 85
Glutamine Synthetase as a Therapeutic Target for Cancer Treatment
Kim, G. W., Lee, D. H., Jeon, Y. H., Yoo, J. H., Kim, S. Y., Lee, S. W., Cho, H. Y., & Kwon, S. H. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22041701 · Cited by 86
Roles of pyruvate carboxylase in human diseases: from diabetes to cancers and infection
Lao-On, U., Attwood, P. V., & Jitrapakdee, S. (2018) · Journal of Molecular Medicine · doi:10.1007/s00109-018-1622-0 · Cited by 85
The mitophagy effector FUNDC1 controls mitochondrial reprogramming and cellular plasticity in cancer cells
Li, J., Agarwal, E., Bertolini, I., Seo, J. H., Caino, M. C., Ghosh, J. C., Kossenkov, A. V., Liu, Q., Tang, H., Goldman, A. R., et al. (2020) · Science Signaling · doi:10.1126/scisignal.aaz8240 · Cited by 83
Fibroblast pyruvate carboxylase is required for collagen production in the tumour microenvironment
Schwörer, S., Pavlova, N. N., Cimino, F. V., King, B., Cai, X., Sizemore, G. M., & Thompson, C. B. (2021) · Nature Metabolism · doi:10.1038/s42255-021-00480-x · Cited by 82
Oncogene-Driven Metabolic Alterations in Cancer
Min, H., & Lee, H. (2017) · Biomolecules & Therapeutics · doi:10.4062/biomolther.2017.211 · Cited by 88
Proteomic analysis of pRb loss highlights a signature of decreased mitochondrial oxidative phosphorylationPreprint
Nicolay, B., Danielian, P. S., Kottakis, F., Lapek, J. D., Sanidas, I., Miles, W. O., Dehnad, M., Tschöp, K., Gierut, J. J., Manning, A. L., et al. (2015) · Genes & Development · doi:10.1101/gad.264127.115 · Cited by 84
Mitochondrial dynamics and metastasis
Altieri, D. C. (2018) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-018-2961-2 · Cited by 88
Metabolic Reprogramming of Non-Hodgkin's B-Cell Lymphomas and Potential Therapeutic Strategies
Ricci, J., & Chiche, J. (2018) · Frontiers in Oncology · doi:10.3389/fonc.2018.00556 · Cited by 87
Fluxomics - New Metabolomics Approaches to Monitor Metabolic Pathways
Emwas, A.-H. M., Szczepski, K., Al-Younis, I. M., Lachowicz, J. I., & Jaremko, M. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.805782 · Cited by 83
Next-generation metabolomics in lung cancer diagnosis, treatment and precision medicine: mini review
Li, Y., Li, K., & Zhang, X. (2017) · Oncotarget · doi:10.18632/oncotarget.22404 · Cited by 81
Dissecting cell-type-specific metabolism in pancreatic ductal adenocarcinoma
Lau, A. N., Li, Z., Danai, L. V., Westermark, A. M., Darnell, A. M., Ferreira, R., Gocheva, V., Sivanand, S., Lien, E. C., Sapp, K. M., et al. (2020) · eLife · doi:10.7554/elife.56782 · Cited by 82
Metabolic pathway analysis using stable isotopes in patients with cancer
Bartman, C., Faubert, B., Rabinowitz, J. D., & DeBerardinis, R. J. (2023) · Nature reviews. Cancer · doi:10.1038/s41568-023-00632-z · Cited by 93
Beyond antioxidant genes in the ancient Nrf2 regulatory network
Lacher, S. E., Lee, J. S., Wang, X., Campbell, M. R., Bell, D. A., & Slattery, M. (2015) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2015.06.044 · Cited by 77
Drug discovery strategies in the field of tumor energy metabolism: Limitations by metabolic flexibility and metabolic resistance to chemotherapy
Amoedo, N. D., Obre, E., & Rossignol, R. (2017) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2017.02.005 · Cited by 76
The Mitochondrial Citrate Carrier SLC25A1/CIC and the Fundamental Role of Citrate in Cancer, Inflammation and Beyond
Mosaoa, R., Kasprzyk-Pawelec, A., Fernandez, H. R., & Avantaggiati, M. L. (2021) · Biomolecules · doi:10.3390/biom11020141 · Cited by 80
MicroRNAs and oncogenic transcriptional regulatory networks controlling metabolic reprogramming in cancers
Pinweha, P., Rattanapornsompong, K., Charoensawan, V., & Jitrapakdee, S. (2016) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2016.05.005 · Cited by 75
Complementary ACSL isoforms contribute to a non-Warburg advantageous energetic status characterizing invasive colon cancer cells
Sánchez‐Martínez, R., Cruz-Gil, S., García-Álvarez, M. S., Reglero, G., & de Molina, A. R. (2017) · Scientific Reports · doi:10.1038/s41598-017-11612-3 · Cited by 72
Metabolic rewiring in mutant Kras lung cancer
Kerr, E. M., & Martins, C. P. (2017) · FEBS Journal · doi:10.1111/febs.14125 · Cited by 76
Application of metabolomics technologies toward cancer prognosis and therapy
Hoang, G., Udupa, S., & Le, A. (2019) · International review of cytology · doi:10.1016/bs.ircmb.2019.07.003 · Cited by 73
Targeting Pyruvate Carboxylase by a Small Molecule Suppresses Breast Cancer Progression
Lin, Q., He, Y., Wang, X., Zhang, Y., Hu, M., Guo, W., He, Y., Zhang, T., Lai, L., Sun, Z., et al. (2020) · Advanced Science · doi:10.1002/advs.201903483 · Cited by 71
Integrated Metabolomics and Proteomics Highlight Altered Nicotinamide- and Polyamine Pathways in Lung Adenocarcinoma
Fahrmann, J. F., Grapov, D., Wanichthanarak, K., DeFelice, B. C., Salemi, M., Rom, W. N., Gandara, D. R., Phinney, B. S., Fiehn, O., Pass, H. I., et al. (2016) · Carcinogenesis · doi:10.1093/carcin/bgw205 · Cited by 74
Mitochondria on the move: emerging paradigms of organelle trafficking in tumour plasticity and metastasis
Altieri, D. C. (2017) · British Journal of Cancer · doi:10.1038/bjc.2017.201 · Cited by 70
Intratumor Heterogeneity in Primary Kidney Cancer Revealed by Metabolic Profiling of Multiple Spatially Separated Samples within Tumors
Okegawa, T., Morimoto, M., Nishizawa, S., Kitazawa, S., Honda, K., Araki, H., Tamura, T., Ando, A., Satomi, Y., Nutahara, K., et al. (2017) · EBioMedicine · doi:10.1016/j.ebiom.2017.04.009 · Cited by 71
Mitochondrial dysfunctions in 7-ketocholesterol-treated 158N oligodendrocytes without or with α-tocopherol: Impacts on the cellular profil of tricarboxylic cycle-associated organic acids, long chain saturated and unsaturated fatty acids, oxysterols, cholesterol and cholesterol precursors
Leoni, V., Nury, T., Véjux, A., Zarrouk, A., Caccia, C., Debbabi, M., Fromont, A., Sghaier, R., Moreau, T., & Lizard, G. (2016) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2016.03.029 · Cited by 70
Stable Isotope Resolved Metabolomics Studies in ex vivo TIssue Slices
Fan, T. W. ‐., Lane, A. N., & Higashi, R. M. (2016) · BIO-PROTOCOL · doi:10.21769/bioprotoc.1730 · Cited by 68
Self-citation
Differential Aspartate Usage Identifies a Subset of Cancer Cells Particularly Dependent on OGDH
Allen, E. L., Ulanet, D., Pirman, D. A., Mahoney, C. E., Coco, J., Si, Y., Chen, Y., Huang, L., Ren, J., Choe, S. E., et al. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.09.052 · Cited by 69
The glycerol backbone of phospholipids derives from noncarbohydrate precursors in starved lung cancer cells
Leithner, K., Triebl, A., Trötzmüller, M., Hinteregger, B., Leko, P., Wieser, B. I., Grasmann, G., Bertsch, A., Züllig, T., Stacher, E., et al. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1719871115 · Cited by 69
Adipocytes reprogram cancer cell metabolism by diverting glucose towards glycerol-3-phosphate thereby promoting metastasis
Mukherjee, A., Bezwada, D., Greco, F., Zandbergen, M., Shen, T., Chiang, C.-Y., Tasdemir, M., Fahrmann, J. F., Grapov, D., Frano, M. R. L., et al. (2023) · Nature Metabolism · doi:10.1038/s42255-023-00879-8 · Cited by 66
A second Warburg‐like effect in cancer metabolism: The metabolic shift of glutamine‐derived nitrogen
Kodama, M., & Nakayama, K. I. (2020) · BioEssays · doi:10.1002/bies.202000169 · Cited by 65
Mass spectrometry analysis shows the biosynthetic pathways supported by pyruvate carboxylase in highly invasive breast cancer cells
Phannasil, P., Ansari, I. H., Azzouny, M. E., Longacre, M. J., Rattanapornsompong, K., Burant, C., MacDonald, M. J., & Jitrapakdee, S. (2016) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2016.11.021 · Cited by 66
Integration of flux measurements to resolve changes in anabolic and catabolic metabolism in cardiac myocytes
Gibb, A., Lorkiewicz, P. K., Zheng, Y., Zhang, X., Bhatnagar, A., Jones, S. P., & Hill, B. G. (2017) · Biochemical Journal · doi:10.1042/bcj20170474 · Cited by 65
In vivo isotope tracing reveals a requirement for the electron transport chain in glucose and glutamine metabolism by tumors
Pachnis, P., Wu, Z., Faubert, B., Tasdogan, A., Gu, W., Shelton, S. D., Solmonson, A., Rao, A. D., Kaushik, A., Rogers, T. J., et al. (2022) · Science Advances · doi:10.1126/sciadv.abn9550 · Cited by 65
Training in metabolomics research. II. Processing and statistical analysis of metabolomics data, metabolite identification, pathway analysis, applications of metabolomics and its future
Barnes, S., Benton, H. P., Casazza, K., Cooper, S. J., Cui, X., Du, X., Engler, J. A., Kabarowski, J. H. S., Li, S., Pathmasiri, W., et al. (2016) · Journal of Mass Spectrometry · doi:10.1002/jms.3780 · Cited by 64
Metabolic interactions in cancer: cellular metabolism at the interface between the microenvironment, the cancer cell phenotype and the epigenetic landscape
Rinaldi, G., Rossi, M., & Fendt, S. (2017) · WIREs Systems Biology and Medicine · doi:10.1002/wsbm.1397 · Cited by 65
Recent advances in cancer metabolism: a technological perspective
Kang, Y. P., Ward, N. P., & DeNicola, G. M. (2018) · Experimental & Molecular Medicine · doi:10.1038/s12276-018-0027-z · Cited by 65
Bioenergetics and translational metabolism: implications for genetics, physiology and precision medicine
Hill, B. G., Shiva, S., Ballinger, S. W., Zhang, J., & Darley-Usmar, V. M. (2019) · Biological Chemistry · doi:10.1515/hsz-2019-0268 · Cited by 66
Distinctly perturbed metabolic networks underlie differential tumor tissue damages induced by immune modulator β-glucan in a two-case ex vivo non-small-cell lung cancer studyPreprint
Fan, T. W. ‐., Warmoes, M. O., Sun, Q., Song, H., Turchan-Cholewo, J. T., Martin, J. T., Mahan, A. L., Higashi, R. M., & Lane, A. N. (2016) · Molecular Case Studies · doi:10.1101/mcs.a000893 · Cited by 62
Self-citation
Air pollution-derived particulate matter dysregulates hepatic Krebs cycle, glucose and lipid metabolism in mice
Reyes-Caballero, H., Rao, X., Sun, Q., Warmoes, M. O., Lin, P., Sussan, T. E., Park, B., Fan, T. W. ‐., Maiseyeu, A., Rajagopalan, S., et al. (2019) · Scientific Reports · doi:10.1038/s41598-019-53716-y · Cited by 64
Self-citation
Single cell metabolism: current and future trends
Ali, A., Davidson, S. M., Fraenkel, E., Gilmore, I. S., Hankemeier, T., Kirwan, J., Lane, A. N., Lanekoff, I., Larion, M., McCall, L., et al. (2022) · Metabolomics · doi:10.1007/s11306-022-01934-3 · Cited by 64
Self-citation
Targeting metabolic vulnerability in mitochondria conquers MEK inhibitor resistance in KRAS-mutant lung cancer
Feng, J., Lian, Z., Xia, X., Lu, Y., Hu, K., Zhang, Y., Liu, Y., Hu, L., Yuan, K., Sun, Z., et al. (2022) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2022.10.023 · Cited by 63
Metabolic and mind shifts
Corbet, C., & Féron, O. (2015) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/mco.0000000000000178 · Cited by 61
Metabolic plasticity maintains proliferation in pyruvate dehydrogenase deficient cells
Rajagopalan, K. N., Egnatchik, R. A., Calvaruso, M. A., Wasti, A., Padanad, M. S., Boroughs, L. K., Ko, B., Hensley, C. T., Acar, M., Hu, Z., et al. (2015) · Cancer & Metabolism · doi:10.1186/s40170-015-0134-4 · Cited by 61
Mitochondrial pyruvate carrier function and cancer metabolism
Rauckhorst, A. J., & Taylor, E. B. (2016) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2016.05.003 · Cited by 59
Exploiting metabolic vulnerabilities for personalized therapy in acute myeloid leukemia
Stuani, L., Sabatier, M., & Sarry, J. (2019) · BMC Biology · doi:10.1186/s12915-019-0670-4 · Cited by 66
The BRAF Inhibitor Vemurafenib Activates Mitochondrial Metabolism and Inhibits Hyperpolarized Pyruvate–Lactate Exchange in BRAF-Mutant Human Melanoma Cells
Delgado‐Goñi, T., Miniotis, M. F., Wantuch, S., Parkes, H. G., Marais, R., Workman, P., Leach, M. O., & Beloueche‐Babari, M. (2016) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-16-0068 · Cited by 58
Phosphorylation of glutaminase by PKCε is essential for its enzymatic activity and critically contributes to tumorigenesis
Han, T., Zhan, W., Gan, M., Liu, F., Yu, B., Chin, Y. E., & Wang, J.-B. (2018) · Cell Research · doi:10.1038/s41422-018-0021-y · Cited by 60
Metabolic reprogramming and Notch activity distinguish between non-small cell lung cancer subtypes
Sellers, K., Allen, T. D., Bousamra, M., Tan, J., Méndez‐Lucas, A., Lin, W., Bah, N. K., Chernyavskaya, Y., MacRae, J. I., Higashi, R. M., et al. (2019) · British Journal of Cancer · doi:10.1038/s41416-019-0464-z · Cited by 57
Self-citation
Metabolic adaptations in cancers expressing isocitrate dehydrogenase mutations
Hvinden, I. C., Cadoux-Hudson, T. A. D., Schofield, C. J., & McCullagh, J. (2021) · Cell Reports Medicine · doi:10.1016/j.xcrm.2021.100469 · Cited by 63
Breath Analysis for Early Detection of Malignant Pleural Mesothelioma: Volatile Organic Compounds (VOCs) Determination and Possible Biochemical Pathways
Gilio, A. D., Catino, A., Lombardi, A., Palmisani, J., Facchini, L., Mongelli, T., Varesano, N., Bellotti, R., Galetta, D., de Gennaro, G., et al. (2020) · Cancers · doi:10.3390/cancers12051262 · Cited by 55
Syntaphilin Ubiquitination Regulates Mitochondrial Dynamics and Tumor Cell Movements
Seo, J. H., Agarwal, E., Bryant, K. G., Caino, M. C., Kim, E. T., Kossenkov, A. V., Tang, H., Languino, L. R., Gabrilovich, D. I., Cohen, A. R., et al. (2018) · Cancer Research · doi:10.1158/0008-5472.can-18-0595 · Cited by 58
Probing the metabolic phenotype of breast cancer cells by multiple tracer stable isotope resolved metabolomics
Lane, A. N., Tan, J. D., Wang, Y., Yan, J., Higashi, R. M., & Fan, T. W. ‐. (2017) · Metabolic Engineering · doi:10.1016/j.ymben.2017.01.010 · Cited by 55
Self-citation
Stable Isotope-Resolved Metabolomics Shows Metabolic Resistance to Anti-Cancer Selenite in 3D Spheroids versus 2D Cell Cultures
Fan, T. W. ‐., El‐Amouri, S. S., Macêdo, J. K. A., Wang, Q. J., Song, H., Cassel, T., & Lane, A. N. (2018) · Metabolites · doi:10.3390/metabo8030040 · Cited by 55
Self-citation
Exploiting metabolic vulnerabilities of Non small cell lung carcinoma
Majem, B., Nadal, E., & Muñoz‐Pinedo, C. (2019) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2019.06.004 · Cited by 57
Nicotinamide nucleotide transhydrogenase regulates mitochondrial metabolism in NSCLC through maintenance of Fe-S protein function
Ward, N. P., Kang, Y. P., Falzone, A., Boyle, T. A., & DeNicola, G. M. (2020) · The Journal of Experimental Medicine · doi:10.1084/jem.20191689 · Cited by 55
Roles of highly expressed PAICS in lung adenocarcinoma
Zhou, S., Yan, Y., Chen, X., Wang, X., Zeng, S., Qian, L., Wei, J., Yang, X., Zhou, Y., Gong, Z., et al. (2019) · Gene · doi:10.1016/j.gene.2018.12.064 · Cited by 53
Pyruvate anaplerosis is a mechanism of resistance to pharmacological glutaminase inhibition in triple-receptor negative breast cancer
Singleton, D. C., Dechaume, A.-L., Murray, P. M., Katt, W. P., Baguley, B. C., & Leung, E. Y. (2020) · BMC Cancer · doi:10.1186/s12885-020-06885-3 · Cited by 56
NMR-based Stable Isotope Resolved Metabolomics in systems biochemistry
Lane, A. N., & Fan, T. W. ‐. (2017) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2017.02.009 · Cited by 54
Self-citation
Including the mitochondrial metabolism of l-lactate in cancer metabolic reprogramming
Lidia de, B. A. R. I., & Atlante, A. (2018) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-018-2831-y · Cited by 52
Inhibition of the ALDH18A1-MYCN positive feedback loop attenuates MYCN -amplified neuroblastoma growth
Guo, Y.-F., Duan, J., Wang, J., Li, L., Wang, D., Liu, X.-Z., Yang, J., Zhang, H., Lv, J., Yang, Y., et al. (2020) · Science Translational Medicine · doi:10.1126/scitranslmed.aax8694 · Cited by 54
NMR and MS-based Stable Isotope-Resolved Metabolomics and applications in cancer metabolism
Lane, A. N., Higashi, R. M., & Fan, T. W. ‐. (2018) · TrAC Trends in Analytical Chemistry · doi:10.1016/j.trac.2018.11.020 · Cited by 52
Self-citation
Tissue of origin dictates GOT1 dependence and confers synthetic lethality to radiotherapy
Nelson, B. S., Lin, L., Kremer, D. M., Sousa, C. M., Cotta‐Ramusino, C., Myers, A. L., Ramos, J., Gao, T., Kovalenko, I., Wilder-Romans, K., et al. (2020) · Cancer & Metabolism · doi:10.1186/s40170-019-0202-2 · Cited by 51
The immunometabolic ecosystem in cancer
Bantug, G. R., & Hess, C. (2023) · Nature Immunology · doi:10.1038/s41590-023-01675-y · Cited by 53
The potential of breath analysis to improve outcome for patients with lung cancer
Antoniou, S., Gaude, E., Ruparel, M., van der Schee, M. P., Janes, S. M., & Rintoul, R. C. (2019) · Journal of Breath Research · doi:10.1088/1752-7163/ab0bee · Cited by 49
The Molecular Mechanism of Metabolic Remodeling in Lung Cancer
Chang, L., Fang, S., & Gu, W. (2020) · Journal of Cancer · doi:10.7150/jca.31406 · Cited by 49
Microanatomic Distribution of Myeloid Heme Oxygenase-1 Protects against Free Radical-Mediated Immunopathology in Human Tuberculosis
Chinta, K. C., Rahman, M. A., Saini, V., Glasgow, J. N., Reddy, V. P., Lever, J. M., Nhamoyebonde, S., Leslie, A. J., Wells, R. M., Traylor, A., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.10.073 · Cited by 43
A systematic flux analysis approach to identify metabolic vulnerabilities in human breast cancer cell lines
Martin, S. D., & McGee, S. L. (2019) · Cancer & Metabolism · doi:10.1186/s40170-019-0207-x · Cited by 48
Isotope tracing reveals glycolysis and oxidative metabolism in childhood tumors of multiple histologies
Johnston, K., Pachnis, P., Tasdogan, A., Faubert, B., Zacharias, L. G., Vu, H., Rodgers-Augustyniak, L. A., Johnson, A., Huang, F., Ricciardo, S., et al. (2021) · Med · doi:10.1016/j.medj.2021.01.002 · Cited by 52
An Asp to Strike Out Cancer? Therapeutic Possibilities Arising from Aspartate’s Emerging Roles in Cell Proliferation and Survival
Helenius, I. T., Madala, H. R., & Yeh, J.-R. J. (2021) · Biomolecules · doi:10.3390/biom11111666 · Cited by 43
Targeting cancer-specific metabolic pathways for developing novel cancer therapeutics
Pal, S., Sharma, A. K., Mathew, S. P., & Jaganathan, B. G. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.955476 · Cited by 50
Loss of thymidine kinase 1 inhibits lung cancer growth and metastatic attributes by reducing GDF15 expression
Malvi, P., Janoštiak, R., Nagarajan, A. G., Cai, G., & Wajapeyee, N. (2019) · PLoS Genetics · doi:10.1371/journal.pgen.1008439 · Cited by 46
Research into cancer metabolomics: Towards a clinical metamorphosis
Olivares, O., Däbritz, J. H. M., King, A., Gottlieb, E., & Halsey, C. (2015) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2015.09.008 · Cited by 45
Reverse engineering the cancer metabolic network using flux analysis to understand drivers of human disease
Badur, M. G., & Metallo, C. M. (2017) · Metabolic Engineering · doi:10.1016/j.ymben.2017.11.013 · Cited by 44
The deubiquitinase JOSD2 is a positive regulator of glucose metabolism
Krassikova, L., Zhang, B., Nagarajan, D., Queiroz, A. L., Kacal, M., Samakidis, E., Vakifahmetoglu-Norberg, H., & Norberg, E. (2020) · Cell Death and Differentiation · doi:10.1038/s41418-020-00639-1 · Cited by 47
Flexibility and Adaptation of Cancer Cells in a Heterogenous Metabolic Microenvironment
Bluemel, G., Mondal, A., & Leithner, K. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22031476 · Cited by 44
Metabolomics: Bridging the Gap between Pharmaceutical Development and Population Health
Tolstikov, V. (2016) · Metabolites · doi:10.3390/metabo6030020 · Cited by 45
Identification of Pyruvate Carboxylase as the Cellular Target of Natural Bibenzyls with Potent Anticancer Activity against Hepatocellular Carcinoma via Metabolic Reprogramming
Sheng, Y., Chen, Y., Zeng, Z., Wu, W., Wang, J., Ma, Y., Lin, Y., Zhang, J., Huang, Y., Li, W., et al. (2021) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.1c01605 · Cited by 44
Analyzing Tumor Metabolism In Vivo
Faubert, B., & DeBerardinis, R. J. (2016) · Annual Review of Cancer Biology · doi:10.1146/annurev-cancerbio-050216-121954 · Cited by 44
Glutamine metabolism via glutaminase 1 in autosomal-dominant polycystic kidney disease
Soomro, I., Sun, Y., Zhai, L., Diggs, L., Hatzivassiliou, G., Thomas, A. G., Rais, R., Slusher, B. S., Somlo, S., & Skolnik, E. Y. (2017) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfx349 · Cited by 43
Reprogramming of Energy Metabolism: Increased Expression and Roles of Pyruvate Carboxylase in Papillary Thyroid Cancer
Strickaert, A., Corbet, C., Spinette, S. A., Craciun, L., Dom, G., Andry, G., Larsimont, D., Wattiez, R., Dumont, J. E., Féron, O., et al. (2019) · Thyroid · doi:10.1089/thy.2018.0435 · Cited by 43
Interrogating in vivo T-cell metabolism in mice using stable isotope labeling metabolomics and rapid cell sorting
Sheldon, R. D., Ma, E. H., DeCamp, L. M., Williams, K. S., & Jones, R. G. (2021) · Nature Protocols · doi:10.1038/s41596-021-00586-2 · Cited by 43
Small Extracellular Vesicle Regulation of Mitochondrial Dynamics Reprograms a Hypoxic Tumor Microenvironment
Bertolini, I., Ghosh, J. C., Kossenkov, A. V., Mulugu, S., Krishn, S. R., Vaira, V., Qin, J., Plow, E. F., Languino, L. R., & Altieri, D. C. (2020) · Developmental Cell · doi:10.1016/j.devcel.2020.07.014 · Cited by 44
Targeting fuel pocket of cancer cell metabolism: A focus on glutaminolysis
Sharma, S., Agnihotri, N., & Kumar, S. (2022) · Biochemical Pharmacology · doi:10.1016/j.bcp.2022.114943 · Cited by 42
Integrative cross-platform analyses identify enhanced heterotrophy as a metabolic hallmark in glioblastoma
Prabhu, A. H., Kant, S., Kesarwani, P., Ahmed, K. A., Forsyth, P. A., Nakano, I., & Chinnaiyan, P. (2018) · Neuro-Oncology · doi:10.1093/neuonc/noy185 · Cited by 38
Metabolomic, transcriptomic and genetic integrative analysis reveals important roles of adenosine diphosphate in haemostasis and platelet activation in non‐small‐cell lung cancer
Hoang, L. T., Domingo‐Sabugo, C., Starren, E. S., Willis‐Owen, S. A. G., Morris‐Rosendahl, D. J., Nicholson, A. G., Cookson, W. O. C. M., & Moffatt, M. F. (2019) · Molecular Oncology · doi:10.1002/1878-0261.12568 · Cited by 39
Chloroformate derivatization for tracing the fate of Amino acids in cells and tissues by multiple stable isotope resolved metabolomics (mSIRM)
Yang, Y., Fan, T. W. ‐., Lane, A. N., & Higashi, R. M. (2017) · Analytica Chimica Acta · doi:10.1016/j.aca.2017.04.014 · Cited by 39
Self-citation
Comprehensive Isotopic Targeted Mass Spectrometry: Reliable Metabolic Flux Analysis with Broad Coverage
Shi, X., Xi, B., Jasbi, P., Turner, C., Jin, Y., & Gu, H. (2020) · Analytical Chemistry · doi:10.1021/acs.analchem.0c01767 · Cited by 40
Evaluation of disease staging and chemotherapeutic response in non-small cell lung cancer from patient tumor-derived metabolomic data
Miller, H. A., Yin, X., Smith, S. A., Hu, X., Zhang, X., Yan, J., Miller, D. M., van Berkel, V. H., & Frieboes, H. B. (2021) · Lung Cancer · doi:10.1016/j.lungcan.2021.04.012 · Cited by 39
Self-citation
Protein networks linking Warburg and reverse Warburg effects to cancer cell metabolism
Johar, D., Elmehrath, A. O., Khalil, R. M., Elberry, M. H., Zaky, S., Shalabi, S. A., & Bernstein, L. H. (2021) · BioFactors · doi:10.1002/biof.1768 · Cited by 42
Increased inflammatory lipid metabolism and anaplerotic mitochondrial activation follow acquired resistance to vemurafenib in BRAF-mutant melanoma cells
Delgado-Goñi, T., Galobart, T. C., Wantuch, S., Normantaite, D., Leach, M. O., Whittaker, S. R., & Beloueche-Babari, M. (2020) · British Journal of Cancer · doi:10.1038/s41416-019-0628-x · Cited by 39
Mechanistic insight into allosteric activation of human pyruvate carboxylase by acetyl-CoA
Chai, P., Lan, P., Li, S., Yao, D., Chang, C., Mi, C., Shen, Y., Ge, S., Wu, J., Lei, M., et al. (2022) · Molecular Cell · doi:10.1016/j.molcel.2022.09.033 · Cited by 39
Tylophorine-based compounds are therapeutic in rheumatoid arthritis by targeting the caprin-1 ribonucleoprotein complex and inhibiting expression of associated c-Myc and HIF-1α
Lee, Y., Guo, H.-C., Zhao, G.-H., Yang, C., Chang, H.-Y., Yang, R., Chen, L., & Lee, S. (2019) · Pharmacological Research · doi:10.1016/j.phrs.2019.104581 · Cited by 38
Long Noncoding RNA CTD-2245E15.3 Promotes Anabolic Enzymes ACC1 and PC to Support Non–Small Cell Lung Cancer Growth
Wang, C., Meng, X., Zhou, Y., Yu, J., Li, Q., Liao, Z., Gu, Y., Han, J., Linghu, S., Jiao, Z., et al. (2021) · Cancer Research · doi:10.1158/0008-5472.can-19-3806 · Cited by 38
Genetic Dissociation of Glycolysis and the TCA Cycle Affects Neither Normal nor Neoplastic Proliferation
Jackson, L. E., Kulkarni, S., Wang, H., Lu, J. L., Dolezal, J. M., Bharathi, S. S., Ranganathan, S., Patel, M. S., Deshpande, R., Alencastro, F., et al. (2017) · Cancer Research · doi:10.1158/0008-5472.can-17-1325 · Cited by 38
Self-citation
Exploring the metabolic alterations in cervical cancer induced by HPV oncoproteins: From mechanisms to therapeutic targets
Gore, M., Kabekkodu, S. P., & Chakrabarty, S. (2025) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2025.189292 · Cited by 41
13C Tracer Studies of Metabolism in Mouse Tumor Xenografts
Lane, A. N., Yan, J., & Fan, T. W. ‐. (2015) · BIO-PROTOCOL · doi:10.21769/bioprotoc.1650 · Cited by 39
Self-citation
1α,25-dihydroxyvitamin D inhibits de novo fatty acid synthesis and lipid accumulation in metastatic breast cancer cells through down-regulation of pyruvate carboxylase
Wilmanski, T. M., Buhman, K. K., Donkin, S. S., Burgess, J. R., & Teegarden, D. (2016) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2016.11.006 · Cited by 37

Authors: Sellers, K., Fox, M. P., Bousamra, M., Slone, S. P., Higashi, R. M., Miller, D. M., Wang, Y., Yan, J., Yuneva, M. O., Deshpande, R., Lane, A. N., & Fan, T. W.-M.
Affiliations: University of Louisville (US)
National Institute for Medical Research (GB)
University of Kentucky (US)
Corresponding author: Lane, Andrew N.
ORCID: Higashi, Richard M.
Miller, Donald M.
Wang, Yali
Yan, Jun
Yuneva, Mariia O.
Lane, Andrew N.
Fan, Teresa W.-M.
Venue: Journal of Clinical Investigation
Publisher: American Society for Clinical Investigation
Published: 2015-01-20
Volume: 125
Issue: 2
Pages: 687-698
ISSN: 0021-9738 (ISSN-L)
DOI: 10.1172/jci72873
PMC: PMC4319441
OpenAlex: W2041729369
Cited by: 497
References: 44
Citations by year: 2026: 20 · 2025: 29 · 2024: 41 · 2023: 23 · 2022: 53 · 2021: 63 · 2020: 57 · 2019: 55 · 2018: 44 · 2017: 53 · 2016: 41 · 2015: 17
FWCI: 17.09
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Journal of Clinical Investigation (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
UKnowledge (University of Kentucky) (submittedVersion)
Funders: National Science Foundation (0447479, 0132295)
University of Louisville (20044)
Francis Crick Institute (10223)
National Institutes of Health
National Cancer Institute (P01CA163223, R01CA118434, R01CA101199, P30CA177558)
National Institute of Diabetes and Digestive and Kidney Diseases (U24DK097215)
National Institute of Environmental Health Sciences (R01ES022191)
National Center for Research Resources (P20RR018733)
Office of Experimental Program to Stimulate Competitive Research
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
Keywords: pyruvate carboxylase, non-small cell lung cancer, anaplerosis, GLS1, TCA cycle, tumor cell proliferation, 13C-labeled glucose, glutamine metabolism, glutathione homeostasis, lipogenesis, nucleotide synthesis, multinucleation, tumor growth
MeSH terms: Animals, Carcinoma, Non-Small-Cell Lung, Citric Acid Cycle, Female, Glucose, Glutathione, Humans, Lung Neoplasms, Male, Neoplasm Proteins, Nucleotides, Pyruvate Carboxylase, Radioactive Tracers, Gene Expression Regulation, Enzymologic, Gene Expression Regulation, Neoplastic, Cell Proliferation, Lipid Metabolism, Mice, HEK293 Cells

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

Pyruvate carboxylase is critical for non–small-cell lung cancer proliferation

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks