The DOI matches its Crossref record; 27 of the 27 references it cites were found in a registry or an index.
Glutamine supports pancreatic cancer growth through a KRAS-regulated metabolic pathway
Open accessAbstract
Cancer cells have metabolic dependencies that distinguish them from their normal counterparts. Among these dependencies is an increased use of the amino acid glutamine to fuel anabolic processes. Indeed, the spectrum of glutamine-dependent tumours and the mechanisms whereby glutamine supports cancer metabolism remain areas of active investigation. Here we report the identification of a non-canonical pathway of glutamine use in human pancreatic ductal adenocarcinoma (PDAC) cells that is required for tumour growth. Whereas most cells use glutamate dehydrogenase (GLUD1) to convert glutamine-derived glutamate into α-ketoglutarate in the mitochondria to fuel the tricarboxylic acid cycle, PDAC relies on a distinct pathway in which glutamine-derived aspartate is transported into the cytoplasm where it can be converted into oxaloacetate by aspartate transaminase (GOT1). Subsequently, this oxaloacetate is converted into malate and then pyruvate, ostensibly increasing the NADPH/NADP(+) ratio which can potentially maintain the cellular redox state. Importantly, PDAC cells are strongly dependent on this series of reactions, as glutamine deprivation or genetic inhibition of any enzyme in this pathway leads to an increase in reactive oxygen species and a reduction in reduced glutathione. Moreover, knockdown of any component enzyme in this series of reactions also results in a pronounced suppression of PDAC growth in vitro and in vivo. Furthermore, we establish that the reprogramming of glutamine metabolism is mediated by oncogenic KRAS, the signature genetic alteration in PDAC, through the transcriptional upregulation and repression of key metabolic enzymes in this pathway. The essentiality of this pathway in PDAC and the fact that it is dispensable in normal cells may provide novel therapeutic approaches to treat these refractory tumours.
Overview
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
Verification
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?
The cited source says what the claim attributes to it.
In the citing paper
“Furthermore, depending on the tissue of origin, cancer cells use various routes of glutamine metabolism. Some have been shown to require an exogenous glutamine supply for malignant proliferation [71,72], whereas others do not [73] and can synthesize it de novo [74].”
From HIF-1-Independent Mechanisms Regulating Metabolic Adaptation in Hypoxic Cancer Cells (2021) · cites this paper as [73]
In the citing paper
“For instance, KRAS-dependent upregulation of Glutamate Oxaloacetate Transaminase 1,2. (GOT) expression in pancreatic cancer facilitates production of aspartate for nucleotide biosynthesis, and allows NADPH generation via ME157,58 (Fig 2).”
From The metabolic landscape of RAS-driven cancers from biology to therapy (2021) · cites this paper as [57]
In the citing paper
“Mouse PDAC tumors driven by mutant Kras also experience metabolic alteration and are dependent on glucose and glutamine (73, 77).”
From KRAS mutation in pancreatic cancer (2021) · cites this paper as [77]
In the citing paper
“combining inhibition of glycolysis with blockade of KRAS effector signaling pathways has shown efficacy in culture and xenograft models197”
From Pancreatic cancer: Advances and challenges (2023) · cites this paper as [197]
In the citing paper
“metabolic inhibition approaches combined with RAS pathway inhibitors have shown strong pre-clinical data and are currently in clinical trials197,224,225”
From Pancreatic cancer: Advances and challenges (2023) · cites this paper as [197]
In the citing paper
“However, under normal and glucose-replete conditions, transamination is the dominant reaction that drives glutamine anaplerosis in cultured cells (79, 80, 81, 82).”
From Regulation and function of the mammalian tricarboxylic acid cycle (2023) · cites this paper as [81]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
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
Self-citationSpencer, P. M., Cameron, J. L., & Lin, L. (2000) · Cited by 7,202
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
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
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
Hidalgo, M. (2010) · New England Journal of Medicine · doi:10.1056/nejmra0901557 · Cited by 2,570
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
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
Self-citationWise, 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
Glutamine addiction: a new therapeutic target in cancer
Wise, D. R., & Thompson, C. B. (2010) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2010.05.003 · Cited by 1,770
Flagged first, then by citations
Cited by
Sorted by citations
Items 201–300 of 1,004
Yin, K., Wang, D., Zhao, H., Wang, Y., Zhang, Y., Liu, Y., Li, B., & Xing, M. (2022) · Environmental Pollution · doi:10.1016/j.envpol.2022.119449 · Cited by 205
Li, W., Li, F., Zhang, X., Lin, H., & Xu, C. S. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00825-8 · Cited by 211
Bott, A. J., Shen, J., Tonelli, C., Zhan, L., Sivaram, N., Jiang, Y.-P., Yu, X., Bhatt, V., Chiles, E., Zhong, H., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.09.056 · Cited by 185
Regulation of autophagy by amino acids and MTOR-dependent signal transduction
Meijer, A. J., Lorin, S., Blommaart, E. F. C., & Codogno, P. (2014) · Amino Acids · doi:10.1007/s00726-014-1765-4 · Cited by 203
Diverting Glycolysis to Combat Oxidative Stress
Mullarky, E., & Cantley, L. C. (2015) · Springer eBooks · doi:10.1007/978-4-431-55651-0_1 · Cited by 197
Self-citationGlutamine depletion regulates Slug to promote EMT and metastasis in pancreatic cancer
Recouvreux, M. V., Moldenhauer, M. R., Galenkamp, K. M. O., Jung, M., James, B., Zhang, Y., Lowy, A., Bagchi, A., & Commisso, C. (2020) · Journal of Experimental Medicine · doi:10.1084/jem.20200388 · Cited by 181
KRAS-related proteins in pancreatic cancer
Mann, K. M., Ying, H., Juan, J. M., Jenkins, N. A., & Copeland, N. G. (2016) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2016.09.003 · Cited by 192
Self-citationRAS: Striking at the Core of the Oncogenic Circuitry
Gimple, R. C., & Wang, X. (2019) · Frontiers in Oncology · doi:10.3389/fonc.2019.00965 · Cited by 174
Self-citationRoles of Aldolase Family Genes in Human Cancers and Diseases
Chang, Y., Yang, Y., Tien, C., Yang, C., & Hsiao, M. (2018) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2018.05.003 · Cited by 190
Cancer Metabolism and the Evasion of Apoptotic Cell Death
Sharma, A., Boise, L., & Shanmugam, M. (2019) · Cancers · doi:10.3390/cancers11081144 · Cited by 202
Lipid signalling drives proteolytic rewiring of mitochondria by YME1L
MacVicar, T., Ohba, Y., Nolte, H., Mayer, F. C., Tatsuta, T., Sprenger, H., Lindner, B., Zhao, Y., Li, J., Bruns, C. J., et al. (2019) · Nature · doi:10.1038/s41586-019-1738-6 · Cited by 187
Famine versus feast: understanding the metabolism of tumors in vivo
Mayers, J. R., & Heiden, M. G. V. (2015) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2015.01.004 · Cited by 190
Modeling cancer metabolism on a genome scale
Yizhak, K., Chaneton, B., Gottlieb, E., & Ruppin, E. (2015) · Molecular Systems Biology · doi:10.15252/msb.20145307 · Cited by 187
Novel therapeutic targets on the horizon for lung cancer
Tan, W.-L., Jain, A., Takano, A. M., Newell, E. W., Iyer, N. G., Lim, W., Tan, E.-H., Zhai, W., Hillmer, A. M., Tam, W. L., et al. (2016) · The Lancet Oncology · doi:10.1016/s1470-2045(16)30123-1 · Cited by 185
A Tale of Two Glutaminases: Homologous Enzymes with Distinct Roles in Tumorigenesis
Katt, W. P., Lukey, M. J., & Cerione, R. A. (2017) · Future Medicinal Chemistry · doi:10.4155/fmc-2016-0190 · Cited by 179
Targeting Glutamine Induces Apoptosis: A Cancer Therapy Approach
Chen, L., & Cui, H. (2015) · International Journal of Molecular Sciences · doi:10.3390/ijms160922830 · Cited by 184
Selective alanine transporter utilization creates a targetable metabolic niche in pancreatic cancer
Parker, S. J., Amendola, C. R., Hollinshead, K. E. R., Yu, Q., Yamamoto, K., Encarnación-Rosado, J., Rose, R. E., LaRue, M. M., Sohn, A. S. W., Biancur, D. E., et al. (2020) · Cancer Discovery · doi:10.1158/2159-8290.cd-19-0959 · Cited by 175
Self-citationWang, Z., Liu, F., Fan, N., Zhou, C., Li, D., MacVicar, T., Dong, Q., Bruns, C. J., & Zhao, Y. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.589508 · Cited by 189
Lactate and glutamine support NADPH generation in cancer cells under glucose deprived conditions
Ying, M., You, D., Zhu, X., Cai, L., Zeng, S., & Hu, X. (2021) · Redox Biology · doi:10.1016/j.redox.2021.102065 · Cited by 186
Oncogene-Directed Alterations in Cancer Cell Metabolism
Nagarajan, A., Malvi, P., & Wajapeyee, N. (2016) · Trends in Cancer · doi:10.1016/j.trecan.2016.06.002 · Cited by 169
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
KRAS Mutant Pancreatic Cancer: No Lone Path to an Effective Treatment
Zeitouni, D., Pylayeva‐Gupta, Y., Der, C. J., & Bryant, K. L. (2016) · Cancers · doi:10.3390/cancers8040045 · Cited by 191
Exploiting the bad eating habits of Ras-driven cancersPreprint
White, E. (2013) · Genes & Development · doi:10.1101/gad.228122.113 · Cited by 183
Lessons from patient-derived xenografts for better in vitro modeling of human cancer
Choi, S. Y. C., Lin, D., Gout, P. W., Collins, C. C., Xu, Y., & Wang, Y. Z. (2014) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2014.09.009 · Cited by 181
Jin, H., Wang, S., Zaal, E. A., Wang, C., Wu, H.-Q., Bosma, A. R., Jochems, F., Isima, N., Jin, G., Lieftink, C., et al. (2020) · eLife · doi:10.7554/elife.56749 · Cited by 183
Ross, S. J., Revenko, A. S., Hanson, L. L., Ellston, R., Staniszewska, A., Whalley, N., Pandey, S. K., Revill, M., Rooney, C., Buckett, L. K., et al. (2017) · Science Translational Medicine · doi:10.1126/scitranslmed.aal5253 · Cited by 177
Effects of tumor metabolic microenvironment on regulatory T cells
Wang, Y., Li, X., Mo, Y., Fan, C., Tang, L. M., Xiong, F., Guo, C. J., Xiang, B., Zhou, M., Ma, J., et al. (2018) · Molecular Cancer · doi:10.1186/s12943-018-0913-y · Cited by 175
Cassim, S., Vučetić, M., Ždralević, M., & Pouysségur, J. (2020) · Cancers · doi:10.3390/cancers12051119 · Cited by 183
Harnessing metabolic dependencies in pancreatic cancers
Encarnación-Rosado, J., & Kimmelman, A. C. (2021) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-021-00431-7 · Cited by 190
Self-citationKim, H. S., Mendiratta, S., Kim, J., Pecot, C. V., Larsen, J. E., Zubovych, I., Seo, B. Y., Kim, J., Eskiocak, B., Chung, H., et al. (2013) · Cell · doi:10.1016/j.cell.2013.09.041 · Cited by 172
OGDHL silencing promotes hepatocellular carcinoma by reprogramming glutamine metabolism
Dai, W., Xu, L., Yu, X., Zhang, G., Guo, H., Liu, H., Song, G., Weng, S., Dong, L., Zhu, J., et al. (2019) · Journal of Hepatology · doi:10.1016/j.jhep.2019.12.015 · Cited by 174
EGFR-Pak signaling selectively regulates glutamine deprivation-induced macropinocytosis
Lee, S.-W., Zhang, Y., Jung, M., Cruz, N., Alas, B., & Commisso, C. (2019) · Developmental Cell · doi:10.1016/j.devcel.2019.05.043 · Cited by 172
Ge, J., Cui, H., Xie, N., Banerjee, S., Guo, S., Dubey, S., Barnes, S., & Liu, G. (2018) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2017-0238oc · Cited by 166
Metabolic rewiring in melanoma
Ratnikov, B. I., Scott, D. A., Osterman, A. L., Smith, J. W., & Ronai, Z. A. (2016) · Oncogene · doi:10.1038/onc.2016.198 · Cited by 176
Lampa, M., Arlt, H., He, T., Ospina, B., Reeves, J., Zhang, B., Murtie, J. C., Deng, G., Barberis, C., Hoffmann, D., et al. (2017) · PLoS ONE · doi:10.1371/journal.pone.0185092 · Cited by 172
miR‐9 regulates ferroptosis by targeting glutamic‐oxaloacetic transaminase GOT1 in melanoma
Zhang, K., Wu, L., Zhang, P., Luo, M., Du, J., Gao, T., O’Connell, D., Wang, G., Wang, H., & Yang, Y. (2018) · Molecular Carcinogenesis · doi:10.1002/mc.22878 · Cited by 171
Addiction to Coupling of the Warburg Effect with Glutamine Catabolism in Cancer Cells
Smith, B., Schafer, X., Ambeskovic, A., Spencer, C. M., Land, H., & Munger, J. C. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.09.045 · Cited by 172
Wang, Y.-Q., Wang, H.-L., Xu, J., Tan, J., Fu, L., Wang, J., Zou, T., Sun, D., Gao, Q., Chen, Y., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-02951-4 · Cited by 169
Targeting SLC1a5 ‐mediated glutamine dependence in non‐small cell lung cancer
Hassanein, M., Qian, J., Hoeksema, M. D., Wang, J., Jacobovitz, M. R., Ji, X., Harris, F. T., Harris, B. K., Boyd, K. L., Chen, H., et al. (2015) · International Journal of Cancer · doi:10.1002/ijc.29535 · Cited by 168
HIF-1-Independent Mechanisms Regulating Metabolic Adaptation in Hypoxic Cancer Cells
Lee, S.-H., Golinska, M., & Griffiths, J. R. (2021) · Cells · doi:10.3390/cells10092371 · Cited by 169
KRAS Controls Pancreatic Cancer Cell Lipid Metabolism and Invasive Potential through the Lipase HSL
Rozeveld, C. N., Johnson, K. M., Zhang, L., & Razidlo, G. L. (2020) · Cancer Research · doi:10.1158/0008-5472.can-20-1255 · Cited by 166
Adapt and conquer: Metabolic flexibility in cancer growth, invasion and evasion
Kreuzaler, P. A., Panina, Y., Segal, J., & Yuneva, M. O. (2019) · Molecular Metabolism · doi:10.1016/j.molmet.2019.08.021 · Cited by 170
Histone lactylation: from tumor lactate metabolism to epigenetic regulation
Yu, X., Yang, J., Xu, J., Pan, H., Wang, W. J., Yu, X., & Shi, S. (2024) · International Journal of Biological Sciences · doi:10.7150/ijbs.91492 · Cited by 187
Módis, K., Bos, E. M., Calzia, E., van Goor, H., Coletta, C., Papapetropoulos, A., Hellmich, M. R., Radermacher, P., Bouillaud, F., & Szabó, C. (2013) · British Journal of Pharmacology · doi:10.1111/bph.12368 · Cited by 163
Dihydroorotate dehydrogenase in oxidative phosphorylation and cancer
Boukalová, Š., Hubáčková, S., Milošević, M., Ezrova, Z., Neužil, J., & Rohlena, J. (2020) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2020.165759 · Cited by 167
Oncogenic regulation of tumor metabolic reprogramming
Tarrado‐Castellarnau, M., de Atauri, P., & Cascante, M. (2016) · Oncotarget · doi:10.18632/oncotarget.10911 · Cited by 165
Regulation and function of autophagy in pancreatic cancer
Li, J., Chen, X., Kang, R., Zeh, H. J., Klionsky, D. J., & Tang, D. (2020) · Autophagy · doi:10.1080/15548627.2020.1847462 · Cited by 167
Uridine-derived ribose fuels glucose-restricted pancreatic cancer
Nwosu, Z. C., Ward, M. H., Sajjakulnukit, P., Poudel, P., Ragulan, C., Kasperek, S., Radyk, M. D., Sutton, D., Menjivar, R. E., Andren, A. C., et al. (2023) · Nature · doi:10.1038/s41586-023-06073-w · Cited by 170
Self-citationTumor Microenvironment Remodeling Enables Bypass of Oncogenic KRAS Dependency in Pancreatic Cancer
Hou, P., Kapoor, A., Zhang, Q., Li, J., Wu, C.-J., Li, J., Lan, Z., Tang, M., Ma, X., Ackroyd, J. J., et al. (2020) · Cancer Discovery · doi:10.1158/2159-8290.cd-19-0597 · Cited by 154
Self-citationMetabolic consequences of oncogenic IDH mutations
Parker, S. J., & Metallo, C. M. (2015) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2015.05.003 · Cited by 162
Developing dietary interventions as therapy for cancer
Taylor, S. R., Falcone, J. N., Cantley, L. C., & Goncalves, M. D. (2022) · Nature reviews. Cancer · doi:10.1038/s41568-022-00485-y · Cited by 168
Self-citationUHRF1 promotes aerobic glycolysis and proliferation via suppression of SIRT4 in pancreatic cancer
Hu, Q., Qin, Y., Ji, S., Xu, W., Liu, W., Sun, Q., Zhang, Z., Liu, M., Ni, Q., Yu, X., et al. (2019) · Cancer Letters · doi:10.1016/j.canlet.2019.03.024 · Cited by 159
Ren, P., Yue, M., Xiao, D., Xiu, R., Gan, L., Liu, H., & Qing, G. (2014) · The Journal of Pathology · doi:10.1002/path.4429 · Cited by 157
Lipid Metabolism and Lipid Droplets in Pancreatic Cancer and Stellate Cells
Sunami, Y., Rebelo, A., & Kleeff, J. H. (2017) · Cancers · doi:10.3390/cancers10010003 · Cited by 157
Yuan, M., Kremer, D. M., Huang, H., Breitkopf, S. B., Ben‐Sahra, I., Manning, B. D., Lyssiotis, C. A., & Asara, J. M. (2019) · Nature Protocols · doi:10.1038/s41596-018-0102-x · Cited by 152
Self-citationGraph Curvature for Differentiating Cancer Networks
Sandhu, R., Georgiou, T. T., Reznik, E., Zhu, L., Kolesov, I., Şenbabaoğlu, Y., & Tannenbaum, A. (2015) · Scientific Reports · doi:10.1038/srep12323 · Cited by 178
Drugging the addict: non‐oncogene addiction as a target for cancer therapy
Nagel, R., Semenova, E. A., & Berns, A. J. M. (2016) · EMBO Reports · doi:10.15252/embr.201643030 · Cited by 161
The plasticity of pancreatic cancer metabolism in tumor progression and therapeutic resistance
Biancur, D. E., & Kimmelman, A. C. (2018) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2018.04.011 · Cited by 152
Self-citationNwosu, Z. C., Battello, N., Rothley, M., Piorońska, W., Sitek, B., Ebert, M. P. A., Hofmann, U., Sleeman, J. P., Wölfl, S., Meyer, C., et al. (2018) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-018-0872-6 · Cited by 156
Liao, M., Liao, W., Xu, N., Li, B., Liu, F., Zhang, S., Wang, Y., Wang, S., Zhu, Y., Chen, D., et al. (2019) · EBioMedicine · doi:10.1016/j.ebiom.2019.01.035 · Cited by 152
Therapeutic Strategies Impacting Cancer Cell Glutamine Metabolism
Lukey, M. J., Wilson, K. F., & Cerione, R. A. (2013) · Future Medicinal Chemistry · doi:10.4155/fmc.13.130 · Cited by 155
Capello, M., Borgogno, S. F., Riganti, C., Chattaragada, M. S., Principe, M., Roux, C., Zhou, W., Petricoin, E. F., Cappello, P., & Novelli, F. (2015) · Oncotarget · doi:10.18632/oncotarget.6798 · Cited by 153
Analysis of clonogenic growth in vitro
Brix, N., Samaga, D., Belka, C., Zitzelsberger, H. F., & Lauber, K. (2021) · Nature Protocols · doi:10.1038/s41596-021-00615-0 · Cited by 152
The role of hypoxia in pancreatic cancer: a potential therapeutic target?
Erkan, M., Kurtoğlu, M., & Kleeff, J. H. (2015) · Expert Review of Gastroenterology & Hepatology · doi:10.1586/17474124.2016.1117386 · Cited by 157
Gouw, A. M., Eberlin, L. S., Margulis, K., Sullivan, D. K., Toal, G. G., Tong, L., Zare, R. N., & Felsher, D. W. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1617709114 · Cited by 152
Wang, M., Wu, H., Fu, G., Zhang, H., Zhou, X., Tang, L., Dong, L., Qin, C., Huang, S., Zhao, L., et al. (2015) · Hepatology · doi:10.1002/hep.28415 · Cited by 149
Hu, H.-F., Ye, Z., Qin, Y., Xu, X.-W., Yu, X.-J., Zhuo, Q.-F., & Ji, S.-R. (2021) · Acta Pharmacologica Sinica · doi:10.1038/s41401-020-00584-2 · Cited by 149
Drp1 Promotes KRas-Driven Metabolic Changes to Drive Pancreatic Tumor Growth
Nagdas, S., Kashatus, J. A., Nascimento, A., Hussain, S. S., Trainor, R. E., Pollock, S. R., Adair, S. J., Michaels, A. D., Sesaki, H., Stelow, E. B., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.07.031 · Cited by 151
O-GlcNAcylation: The Sweet Side of the Cancer
de Queiroz, R. M., Carvalho, Ã., & Dias, W. B. (2014) · Frontiers in Oncology · doi:10.3389/fonc.2014.00132 · Cited by 151
FoxO3 coordinates metabolic pathways to maintain redox balance in neural stem cells
Yeo, H., Lyssiotis, C. A., Zhang, Y., Ying, H., Asara, J. M., Cantley, L. C., & Paik, J.-H. (2013) · The EMBO Journal · doi:10.1038/emboj.2013.186 · Cited by 148
Self-citationRedox control of glutamine utilization in cancer
Alberghina, L., & Gaglio, D. (2014) · Cell Death and Disease · doi:10.1038/cddis.2014.513 · Cited by 150
Goji, T., Takahara, K., Negishi, M., & Katoh, H. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.m117.814392 · Cited by 150
Exploiting Metabolic Vulnerabilities of Cancer with Precision and Accuracy
Wolpaw, A. J., & Dang, C. V. (2017) · Trends in Cell Biology · doi:10.1016/j.tcb.2017.11.006 · Cited by 151
Metabolism-Based Therapeutic Strategies Targeting Cancer Stem Cells
Jagušt, P., de Luxán‐Delgado, B., Parejo-Alonso, B., & Sancho, P. (2019) · Frontiers in Pharmacology · doi:10.3389/fphar.2019.00203 · Cited by 151
Regulation of Cellular Metabolism and Hypoxia by p53Preprint
Humpton, T. J., & Vousden, K. H. (2016) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a026146 · Cited by 154
Cancer’s Fuel Choice: New Flavors for a Picky Eater
DeNicola, G. M., & Cantley, L. C. (2015) · Molecular Cell · doi:10.1016/j.molcel.2015.10.018 · Cited by 149
Self-citationCarnitine palmitoyltransferase 1C: From cognition to cancer
Casals, N., Zammit, V. A., Herrero, L., Fadó, R., Rodríguez‐Rodríguez, R., & Serra, D. (2015) · Progress in Lipid Research · doi:10.1016/j.plipres.2015.11.004 · Cited by 149
Nagarajan, A. G., Dogra, S. K., Sun, L., Gandotra, N., Ho, T., Cai, G., Cline, G. W., Kumar, P., Cowles, R. A., & Wajapeyee, N. (2017) · Molecular Cell · doi:10.1016/j.molcel.2017.07.014 · Cited by 145
Novel Insights on the Use of L-Asparaginase as an Efficient and Safe Anti-Cancer Therapy
Trimpont, M. V., Peeters, E., Visser, Y. D., Schalk, A. M., Mondelaers, V., Moerloose, B. D., Lavie, A., Lammens, T., Goossens, S., & Vlierberghe, P. V. (2022) · Cancers · doi:10.3390/cancers14040902 · Cited by 143
KRAS-Driven Metabolic Rewiring Reveals Novel Actionable Targets in Cancer
Pupo, E., Avanzato, D., Middonti, E., Bussolino, F., & Lanzetti, L. (2019) · Frontiers in Oncology · doi:10.3389/fonc.2019.00848 · Cited by 151
Feng, M., Xiong, G., Cao, Z., Yang, G., Zheng, S., Qiu, J., You, L., Zheng, L., Zhang, T., & Zhao, Y. (2018) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-018-0947-4 · Cited by 141
Perspectives in the treatment of pancreatic adenocarcinoma
Arregui, A. C. (2015) · World Journal of Gastroenterology · doi:10.3748/wjg.v21.i31.9297 · Cited by 146
Sormendi, S., & Wielockx, B. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00040 · Cited by 147
ME1 Regulates NADPH Homeostasis to Promote Gastric Cancer Growth and Metastasis
Lu, Y., Ju, H., Liu, Z., Chen, D.-L., Wang, Y., Zhao, Q., Wu, Q.-N., Zeng, Z.-L., Qiu, H.-B., Hu, P.-S., et al. (2018) · Cancer Research · doi:10.1158/0008-5472.can-17-3155 · Cited by 143
CD9 identifies pancreatic cancer stem cells and modulates glutamine metabolism to fuel tumour growth
Wang, V. M.-Y., Ferreira, R. M. M., Almagro, J., Evan, T., Legrave, N. M., Thin, M. Z., Frith, D., Carvalho, J., Barry, D. J., Snijders, A. P., et al. (2019) · Nature Cell Biology · doi:10.1038/s41556-019-0407-1 · Cited by 142
Non-oncogene Addiction to SIRT3 Plays a Critical Role in Lymphomagenesis
Li, M., Chiang, Y., Lyssiotis, C. A., Teater, M. R., Hong, J. Y., Shen, H., Wang, L., Hu, J., Jing, H., Chen, Z., et al. (2019) · Cancer Cell · doi:10.1016/j.ccell.2019.05.002 · Cited by 143
Self-citationSIRT5 stabilizes mitochondrial glutaminase and supports breast cancer tumorigenesis
Greene, K. S., Lukey, M. J., Wang, X., Blank, B. S., Druso, J. E., Lin, M.-C. J., Stalnecker, C. A., Zhang, C., Abril, Y. L. N., Erickson, J. W., et al. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1911954116 · Cited by 138
Self-citationNitric Oxide: The Forgotten Child of Tumor Metabolism
Rizi, B. S., Achreja, A., & Nagrath, D. (2017) · Trends in cancer · doi:10.1016/j.trecan.2017.07.005 · Cited by 140
Fu, Y., Liu, S., Zeng, S., & Shen, H. (2018) · Molecular Cancer · doi:10.1186/s12943-018-0815-z · Cited by 137
Obre, E., & Rossignol, R. (2015) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2014.12.008 · Cited by 137
Ornithine aminotransferase supports polyamine synthesis in pancreatic cancer
Lee, M.-S., Dennis, C., Naqvi, I., Dailey, L., Lorzadeh, A., Ye, G., Zaytouni, T., Adler, A., Hitchcock, D. S., Lin, L., et al. (2023) · Nature · doi:10.1038/s41586-023-05891-2 · Cited by 143
Analytical Metabolomics and Applications in Health, Environmental and Food Science
Fraga‐Corral, M., Carpena, M., Garcia‐Oliveira, P., Pereira, A. G., Prieto, M. A., & Simal‐Gándara, J. (2020) · Critical Reviews in Analytical Chemistry · doi:10.1080/10408347.2020.1823811 · Cited by 145
Raho, S., Capobianco, L., Malivindi, R., Vozza, A., Piazzolla, C., Leonardis, F. D., Gorgoglione, R., Scarcia, P., Pezzuto, F., Agrimi, G., et al. (2020) · Nature Metabolism · doi:10.1038/s42255-020-00315-1 · Cited by 138
The Relationship of Redox With Hallmarks of Cancer: The Importance of Homeostasis and Context
Xing, F., Hu, Q., Qin, Y., Xu, J., Zhang, B., Yu, X., & Wang, W. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.862743 · Cited by 142
Autophagy and Cancer Metabolism
Goldsmith, J., Levine, B., & Debnath, J. (2014) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/b978-0-12-416618-9.00002-9 · Cited by 139
Targeting metabolic reprogramming in KRAS-driven cancers
Kawada, K., Toda, K., & Sakai, Y. (2017) · International Journal of Clinical Oncology · doi:10.1007/s10147-017-1156-4 · Cited by 140
Draoui, N., de Zeeuw, P., & Carmeliet, P. (2017) · Open Biology · doi:10.1098/rsob.170219 · Cited by 143
The biological underpinnings of therapeutic resistance in pancreatic cancerPreprint
Beatty, G. L., Werba, G., Lyssiotis, C. A., & Simeone, D. M. (2021) · Genes & Development · doi:10.1101/gad.348523.121 · Cited by 139
Self-citationMetabolism addiction in pancreatic cancer
Blum, R., & Kloog, Y. (2014) · Cell Death and Disease · doi:10.1038/cddis.2014.38 · Cited by 138
Hopefully devoted to Q: targeting glutamine addiction in cancer
Still, E. R., & Yuneva, M. O. (2017) · British Journal of Cancer · doi:10.1038/bjc.2017.113 · Cited by 142
Metadata
- Authors
- Son, J., Lyssiotis, C. A., Ying, H., Wang, X., Hua, S., Ligorio, M., Perera, R. M., Ferrone, C. R., Mullarky, E., Shyh-Chang, N., Kang, Y., Fleming, J. B., Bardeesy, N., Asara, J. M., Haigis, M. C., DePinho, R. A., Cantley, L. C., & Kimmelman, A. C.
- Affiliations
- Dana-Farber Cancer Institute (US)
- Beth Israel Deaconess Medical Center (US)
- The University of Texas MD Anderson Cancer Center (US)
- Massachusetts General Hospital (US)
- Harvard University (US)
- Corresponding author
- Cantley, Lewis C.
- Kimmelman, Alec C.
- ORCID
- Venue
- Nature
- Published
- 2013-03-27
- Volume
- 496
- Issue
- 7443
- Pages
- 101-105
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3656466
- OpenAlex
- W2014988241
- Cited by
- 1,990
- References
- 27
- Citations by year
- 2026: 130 · 2025: 143 · 2024: 138 · 2023: 169 · 2022: 193 · 2021: 209 · 2020: 169 · 2019: 162 · 2018: 141 · 2017: 144 · 2016: 152 · 2015: 112 · 2014: 95 · 2013: 31
- FWCI
- 45.68
- Type
- journal article
- Language
- en
- Update notices
- erratum (2013-06-12)
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Cancer Institute (T32CA009382, R01CA157490, P01CA120964, P01CA117969, P30CA006516)
- National Institute of General Medical Sciences (R01GM056203)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Keywords
- pancreatic ductal adenocarcinoma, glutamine metabolism, KRAS, tumor metabolic reprogramming, oxaloacetate, NADPH/NADP+ ratio, redox homeostasis, glutamine deprivation, reactive oxygen species, glutathione, tumor growth
- MeSH terms
- Adenocarcinoma, Aspartate Aminotransferases, Citric Acid Cycle, Glutamate Dehydrogenase, Glutamine, Homeostasis, Humans, Ketoglutaric Acids, Oncogenes, Oxidation-Reduction, Pancreatic Neoplasms, Proto-Oncogene Proteins, Oncogene Protein p21(ras), Proto-Oncogene Proteins p21(ras), Reactive Oxygen Species, ras Proteins, Cell Line, Tumor, Cell Proliferation, Metabolic Networks and Pathways
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
