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
Cited by
Sorted by citations
Items 501–600 of 1,004
Santana-Codina, N., Chandhoke, A. S., Yu, Q., Małachowska, B., Kuljanin, M., Gikandi, A., Stańczak, M., Gableske, S., Jedrychowski, M. P., Scott, D. A., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.03.021 · Cited by 77
Pathological and Molecular Evaluation of Pancreatic Neoplasms
Rishi, A., Goggins, M., Wood, L. D., & Hruban, R. H. (2014) · Seminars in Oncology · doi:10.1053/j.seminoncol.2014.12.004 · Cited by 79
Exploiting pancreatic cancer metabolism: challenges and opportunities
Santis, M. C. D., Bockorny, B., Hirsch, E., Cappello, P., & Martini, M. (2024) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2024.03.008 · Cited by 85
Metabolic Adaptation to Nutritional Stress in Human Colorectal Cancer
Miyo, M., Konno, M., Nishida, N., Sueda, T., Noguchi, K., Matsui, H., Colvin, H. S., Kawamoto, K., Koseki, J., Haraguchi, N., et al. (2016) · Scientific Reports · doi:10.1038/srep38415 · Cited by 77
Exploiting tumor metabolism: challenges for clinical translation
Heiden, M. G. V. (2013) · Journal of Clinical Investigation · doi:10.1172/jci72391 · Cited by 79
Broekgaarden, M., Anbil, S. R., Bulin, A., Obaid, G., Mai, Z., Baglo, Y., Rizvi, I., & Hasan, T. G. (2019) · Biomaterials · doi:10.1016/j.biomaterials.2019.119421 · Cited by 78
Yuan, Y., Wang, L., Ge, D., Tan, L., Cao, B., Fan, H. X., & Xue, L. (2020) · Cancer Letters · doi:10.1016/j.canlet.2020.12.012 · Cited by 76
Operation of a TCA cycle subnetwork in the mammalian nucleus
Kafkia, E., Andrés‐Pons, A., Ganter, K., Seiler, M., Smith, T. S., Andrejeva, A., Jouhten, P., Pereira, F. M., Franco, C., Kuroshchenkova, A., et al. (2022) · Science Advances · doi:10.1126/sciadv.abq5206 · Cited by 76
Metastasis in Pancreatic Ductal Adenocarcinoma: Current Standing and Methodologies
Pereira, M. A., & Chio, I. I. C. (2019) · Genes · doi:10.3390/genes11010006 · Cited by 75
Mitochondria: Insights into Crucial Features to Overcome Cancer Chemoresistance
Genovese, I., Carinci, M., Modesti, L., Aguiari, G., Pinton, P., & Giorgi, C. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22094770 · Cited by 77
Soft Tissue Sarcoma: An Insight on Biomarkers at Molecular, Metabolic and Cellular Level
Pillozzi, S., Bernini, A., Palchetti, I., Crociani, O., Antonuzzo, L., Campanacci, D. A., & Scoccianti, G. (2021) · Cancers · doi:10.3390/cancers13123044 · Cited by 78
Autophagy in cancer cell remodeling and quality control
Hernandez, G. A., & Perera, R. M. (2022) · Molecular Cell · doi:10.1016/j.molcel.2022.03.023 · Cited by 73
Self-citationInterplay of oxidative stress and antioxidant mechanisms in cancer development and progression
Jomová, K., Alomar, S. Y., Valko, R., Fresser, L., Nepovimová, E., Kuča, K., & Valko, M. (2025) · Archives of Toxicology · doi:10.1007/s00204-025-04146-5 · Cited by 103
Role of Increased n-acetylaspartate Levels in Cancer
Zand, B., Previs, R. A., Zacharias, N. M., Rupaimoole, R., Mitamura, T., Nagaraja, A. S., Guindani, M., Dalton, H. J., Yang, L., Baddour, J., et al. (2016) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djv426 · Cited by 78
Miranda, V. D. C., Braghiroli, M. I., Faria, L. D. B. B., Bariani, G. M., Alex, A. K., Neto, J. E. B., Capareli, F. C., Sabbaga, J., dos Santos, J. F. L., Hoff, P. M., et al. (2016) · Clinical Colorectal Cancer · doi:10.1016/j.clcc.2016.04.011 · Cited by 75
Metabolism in cancer metastasis: bioenergetics, biosynthesis, and beyond
Teoh, S. T., & Lunt, S. Y. (2017) · WIREs Systems Biology and Medicine · doi:10.1002/wsbm.1406 · Cited by 77
Lkb1 deficiency confers glutamine dependency in polycystic kidney disease
Flowers, E., Sudderth, J., Zacharias, L. G., Mernaugh, G., Zent, R., DeBerardinis, R. J., & Carroll, T. J. (2018) · Nature Communications · doi:10.1038/s41467-018-03036-y · Cited by 77
Kim, M., Gwak, J., Hwang, S., Yang, S., & Jeong, S. M. (2019) · Oncogene · doi:10.1038/s41388-019-0751-4 · Cited by 74
Zhou, X., Curbo, S., Li, F., Krishnan, S., & Karlsson, A. (2018) · BMC Cancer · doi:10.1186/s12885-018-4443-1 · Cited by 76
Links between cancer metabolism and cisplatin resistance
Cocetta, V., Ragazzi, E., & Montopoli, M. (2020) · International review of cytology · doi:10.1016/bs.ircmb.2020.01.005 · Cited by 77
Xu, R., Yang, J., Ren, B., Wang, H., Yang, G., Chen, Y., You, L., & Zhao, Y. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.572722 · Cited by 74
Roy, I., McAllister, D. M., Gorse, E., Dixon, K. J., Piper, C., Zimmerman, N. P., Getschman, A. E., Tsai, S., Engle, D. D., Evans, D. B., et al. (2015) · Cancer Research · doi:10.1158/0008-5472.can-14-2645 · Cited by 74
Chao, C., Zatarain, J. R., Ding, Y., Coletta, C., Mrazek, A. A., Druzhyna, N., Johnson, P. R., Chen, H., Hellmich, J. L., Asimakopoulou, A., et al. (2016) · Molecular Medicine · doi:10.2119/molmed.2016.00102 · Cited by 74
Metabolic rewiring in mutant Kras lung cancer
Kerr, E. M., & Martins, C. P. (2017) · FEBS Journal · doi:10.1111/febs.14125 · Cited by 76
How glucose, glutamine and fatty acid metabolism shape blood and lymph vessel development
Teuwen, L.-A. M. N., Geldhof, V., & Carmeliet, P. (2017) · Developmental Biology · doi:10.1016/j.ydbio.2017.12.001 · Cited by 75
Inhibition of glutaminolysis in combination with other therapies to improve cancer treatment
Shen, Y., Chen, C., Huang, Y., Evans, E. E., Cheng, C., Chuang, Y.-J., Zhang, C., & Le, A. (2021) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2021.01.006 · Cited by 75
Byun, J., Choi, Y., Kang, Y. N., Jang, B. K., Kang, K. J., Jeon, Y. H., Lee, H., Jeon, J., Koo, S., Jeong, W., et al. (2014) · Hepatology · doi:10.1002/hep.27577 · Cited by 75
Self-citationSignaling Pathways Regulating Redox Balance in Cancer Metabolism
Santis, M. C. D., Porporato, P. E., Martini, M., & Morandi, A. (2018) · Frontiers in Oncology · doi:10.3389/fonc.2018.00126 · Cited by 77
Jonckheere, N., Vasseur, R., & SEUNINGEN, I. V. (2017) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2017.01.002 · Cited by 73
Colorectal cancer cells respond differentially to autophagy inhibition in vivo
Lauzier, A., Normandeau-Guimond, J., Vaillancourt‐Lavigueur, V., Boivin, V., Charbonneau, M., Rivard, N., Scott, M. S., Dubois, C. M., & Jean, S. (2019) · Scientific Reports · doi:10.1038/s41598-019-47659-7 · Cited by 75
Network-based metabolic characterization of renal cell carcinoma
Pandey, N., Lanke, V., & Vinod, P. K. U. (2020) · Scientific Reports · doi:10.1038/s41598-020-62853-8 · Cited by 71
Prasad, A., Khatua, A., Mohanta, Y. K., Saravanan, M., Meena, R., & Ghosh, I. (2022) · Nanoscale · doi:10.1039/d2nr02150a · Cited by 72
Kong, B., Qia, C., Erkan, M., Kleeff, J. H., & Michalski, C. W. (2013) · Frontiers in Physiology · doi:10.3389/fphys.2013.00246 · Cited by 73
Synthetic lethality in KRas-driven cancer cells created by glutamine deprivation
Mukhopadhyay, S., Saqcena, M., & Foster, D. A. (2015) · Oncoscience · doi:10.18632/oncoscience.253 · Cited by 61
Fokas, E., O’Neill, E., Gordon-Weeks, A. N., Mukherjee, S., McKenna, W. G., & Muschel, R. J. (2014) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2014.12.001 · Cited by 75
NF-Y activates genes of metabolic pathways altered in cancer cells
Benatti, P., Chiaramonte, M. L., Lorenzo, M., Hartley, J. A., Hochhauser, D., Gnesutta, N., Mantovani, R., Imbriano, C., & Dolfini, D. (2015) · Oncotarget · doi:10.18632/oncotarget.6453 · Cited by 72
Metabolic signatures of human breast cancer
Mishra, P., & Ambs, S. (2015) · Molecular & Cellular Oncology · doi:10.4161/23723556.2014.992217 · Cited by 70
Lee, B., Mahmud, I., Marchica, J., Dereziński, P., Qi, F., Wang, F., Joshi, P. K., Valerio, F., Rivera, I., Patel, V., et al. (2020) · Scientific Reports · doi:10.1038/s41598-020-60616-z · Cited by 70
Self-citationTargeting KRAS: The Elephant in the Room of Epithelial Cancers
Merz, V., Gaule, M., Zecchetto, C., Cavaliere, A., Casalino, S., Pesoni, C., Contarelli, S., Sabbadini, F., Bertolini, M., Mangiameli, D., et al. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.638360 · Cited by 74
Targeting cancer metabolic pathways for improving chemotherapy and immunotherapy
Luo, Z., Eichinger, K. M., Zhang, A., & Li, S. (2023) · Cancer Letters · doi:10.1016/j.canlet.2023.216396 · Cited by 71
Oral bacteria accelerate pancreatic cancer development in mice
Saba, E., Farhat, M., Daoud, A., Khashan, A., Forkush, E., Menahem, N. H., Makkawi, H., Pandi, K., Angabo, S., Kawasaki, H., et al. (2024) · Gut · doi:10.1136/gutjnl-2023-330941 · Cited by 78
Targeting KRAS: from metabolic regulation to cancer treatment
Shi, Y., Zheng, H., Wang, T., Zhou, S., Zhao, S., Li, M., & Cao, B. (2025) · Molecular Cancer · doi:10.1186/s12943-024-02216-3 · Cited by 81
Ju, H., Zhuang, Z.-N., Li, H., Tian, T., Lu, Y., Fan, X.-Q., Zhou, H. S., Mo, H., Sheng, H., Chiao, P. J., et al. (2016) · Cancer Letters · doi:10.1016/j.canlet.2016.05.024 · Cited by 70
Heras, J. D. L., Aldamiz-Echevarria, L. J., Martínez‐Chantar, M. L., & Delgado, T. C. (2016) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1080/17425255.2017.1262843 · Cited by 70
Carvalho, T. M. A., Molfetta, D. D., Greco, M. R., Koltai, T., Alfarouk, K. O., Reshkin, S. J., & Cardone, R. A. (2021) · Cancers · doi:10.3390/cancers13236135 · Cited by 76
Regulation of Ferroptosis by Amino Acid Metabolism in Cancer
Yang, J., Dai, X., Xu, H., Tang, Q., & Bi, F. (2022) · International Journal of Biological Sciences · doi:10.7150/ijbs.64982 · Cited by 70
The Tumor Microenvironment in Colorectal Cancer Therapy
Pedrosa, L., Esposito, F. M., Thomson, T. M., & Maurel, J. (2019) · Cancers · doi:10.3390/cancers11081172 · Cited by 73
Metabolic Alterations in Pancreatic Cancer Progression
Vernucci, E., Abrego, J., Gunda, V., Shukla, S. K., Dasgupta, A., Rai, V., Chaika, N. V., Buettner, K. B., Illies, A. L., Yu, F., et al. (2019) · Cancers · doi:10.3390/cancers12010002 · Cited by 69
Hoerner, C. R., Chen, V. J., & Fan, A. C. (2019) · Kidney Cancer · doi:10.3233/kca-180043 · Cited by 68
Dong, W., Keibler, M. A., & Stephanopoulos, G. N. (2017) · Metabolic Engineering · doi:10.1016/j.ymben.2017.02.002 · Cited by 69
Computational Model Predicts the Effects of Targeting Cellular Metabolism in Pancreatic Cancer
Roy, M., & Finley, S. D. (2017) · Frontiers in Physiology · doi:10.3389/fphys.2017.00217 · Cited by 70
GLS2 is protumorigenic in breast cancers
Dias, M. M., Adamóski, D., dos Reis, L. M., Ascenção, C. F. R., de Oliveira, K. R. S., Mafra, A. C. P., Bastos, A. C. D. S., Quintero, M., Cassago, C. A. D. G., Ferreira, I. M., et al. (2019) · Oncogene · doi:10.1038/s41388-019-1007-z · Cited by 68
Li, X., Zhu, H., Sun, W., Yang, X., Nie, Q. H., & Fang, X. (2021) · Cancer Cell International · doi:10.1186/s12935-021-02121-5 · Cited by 69
Ganguly, K., Bhatia, R., Rauth, S., Kisling, A., Atri, P., Thompson, C. M., Vengoji, R., Krishn, S. R., Shinde, D. D., Thomas, V. C., et al. (2021) · Gastroenterology · doi:10.1053/j.gastro.2021.09.017 · Cited by 67
Guaragnella, N., Palermo, V., Galli, A., Moro, L., Mazzoni, C., & Giannattasio, S. (2013) · FEMS Yeast Research · doi:10.1111/1567-1364.12094 · Cited by 75
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
Diabetes, pancreatic cancer, and metformin therapy
Gong, J., Robbins, L., Lugea, A., Waldron, R. T., Jeon, C. Y., & Pandol, S. J. (2014) · Frontiers in Physiology · doi:10.3389/fphys.2014.00426 · Cited by 71
Genetics and Biology of Pancreatic Ductal Adenocarcinoma
Dunne, R. F., & Hezel, A. F. (2015) · Hematology/Oncology Clinics of North America · doi:10.1016/j.hoc.2015.04.003 · Cited by 68
The Role of Extracellular Vesicles in Metabolic Reprogramming of the Tumor Microenvironment
Fridman, E., Ginini, L., & Gil, Z. (2022) · Cells · doi:10.3390/cells11091433 · Cited by 69
Li, G., Gan, Y., Fan, Y., Wu, Y., Lin, H., Song, Y., Cai, X., Yu, X., Pan, W., Yao, M., et al. (2015) · Scientific Reports · doi:10.1038/srep07856 · Cited by 67
Saqcena, M., Mukhopadhyay, S., Hosny, C., Alhamed, A., Chatterjee, A., & Foster, D. A. (2015) · Oncogene · doi:10.1038/onc.2014.207 · Cited by 67
Adipocytes promote pancreatic cancer cell proliferation via glutamine transfer
Meyer, K. A., Neeley, C. K., Baker, N. A., Washabaugh, A. R., Flesher, C. G., Nelson, B. S., Frankel, T. L., Lumeng, C. N.-K., Lyssiotis, C. A., Wynn, M. L., et al. (2016) · Biochemistry and Biophysics Reports · doi:10.1016/j.bbrep.2016.06.004 · Cited by 66
Self-citationGrinde, M. T., Hilmarsdóttir, B., Tunset, H. M., Henriksen, I. M., Kim, J., Haugen, M. H., Rye, M. B., Mælandsmo, G. M., & Moestue, S. A. (2019) · Breast Cancer Research · doi:10.1186/s13058-019-1141-0 · Cited by 65
Liu, J., Luo, X., Guo, R., Jing, W., & Lu, H. (2020) · Journal of Proteome Research · doi:10.1021/acs.jproteome.0c00394 · Cited by 66
The glucose transporter GLUT1 is required for ErbB2-induced mammary tumorigenesis
Wellberg, E. A., Johnson, S. J., Finlay-Schultz, J., Lewis, A. S., Terrell, K. L., Sartorius, C. A., Abel, E. D., Muller, W. J., & Anderson, S. M. (2016) · Breast Cancer Research · doi:10.1186/s13058-016-0795-0 · Cited by 65
Mitochondrial mutations and metabolic adaptation in pancreatic cancer
Initiative, A. P. C. G., Hardie, R., van Dam, E., Cowley, M. J., Han, T.-L., Balaban, S., Pajic, M., Pinese, M., Iconomou, M., Shearer, R. F., et al. (2017) · Cancer & Metabolism · doi:10.1186/s40170-017-0164-1 · Cited by 69
Regulation of hepatic stellate cell proliferation and activation by glutamine metabolism
Li, J., Ghazwani, M., Liu, K., Huang, Y., Chang, N., Fan, J., He, F., Li, L., Bu, S., Xie, W., et al. (2017) · PLoS ONE · doi:10.1371/journal.pone.0182679 · Cited by 69
Sung-Rae, C., Chae, J. S., Shin, H. C., Shin, Y., Song, H., Kim, Y.-W., Yoo, B. C., Roh, K., Cho, S., Kil, E., et al. (2018) · Scientific Reports · doi:10.1038/s41598-018-29386-7 · Cited by 66
LRH-1-dependent programming of mitochondrial glutamine processing drives liver cancerPreprint
Xu, P., Oosterveer, M. H., Stein, S. M. A., Demagny, H., Ryu, D., Moullan, N., Wang, X., Can, E., Zamboni, N., Comment, A., et al. (2016) · Genes & Development · doi:10.1101/gad.277483.116 · Cited by 65
Self-citationCancer cell metabolism: Rewiring the mitochondrial hub
Oliveira, G. L., Coelho, A. R., Marques, R., & Oliveira, P. J. (2020) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2020.166016 · Cited by 65
Evan, T., Wang, V. M.-Y., & Behrens, A. (2022) · Oncogene · doi:10.1038/s41388-022-02448-x · Cited by 66
The role of mitochondrial electron transport in tumorigenesis and metastasis
Tan, A. S., Baty, J. W., & Berridge, M. V. (2013) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2013.10.016 · Cited by 65
Neoplasms of the Exocrine Pancreas
Wolff, R. A., Crane, C. H., Li, D., Evans, D. B., Maitra, A., & Tsai, S. (2017) · Wiley eBooks · doi:10.1002/9781119000822.hfcm094 · Cited by 64
Stalnecker, C. A., Grover, K. R., Edwards, A. C., Coleman, M. F., Yang, R., DeLiberty, J. M., Papke, B., Goodwin, C. M., Pierobon, M., Petricoin, E. F., et al. (2021) · Cancer Research · doi:10.1158/0008-5472.can-21-1443 · Cited by 64
Role of Mitochondrial Stress Response in Cancer Progression
Lee, Y. G., Park, D. H., & Chae, Y. C. (2022) · Cells · doi:10.3390/cells11050771 · Cited by 67
Kuna, R. S., Kumar, A., Gálvez, H., Wessendorf-Rodriguez, K. A., Green, C. R., McGregor, G. H., Cordes, T., Shaw, R. J., Svensson, R. U., & Metallo, C. M. (2023) · Science Advances · doi:10.1126/sciadv.adf0138 · Cited by 63
Chakrabarti, G. (2015) · Radiation Oncology · doi:10.1186/s13014-015-0457-x · Cited by 63
Glucose-independent Acetate Metabolism Promotes Melanoma Cell Survival and Tumor Growth
Lakhter, A. J., Hamilton, J., Konger, R. L., Brustovetsky, N., Broxmeyer, H. E., & Naidu, S. R. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.712166 · Cited by 71
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
Tsai, P.-Y., Lee, M.-S., Jadhav, U., Naqvi, I., Madha, S., Adler, A., Mistry, M., Naumenko, S., Lewis, C. A., Hitchcock, D. S., et al. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2003014118 · Cited by 67
NaCT/SLC13A5 facilitates citrate import and metabolism under nutrient-limited conditions
Kumar, A., Cordes, T., Thalacker‐Mercer, A. E., Pajor, A. M., Murphy, A. N., & Metallo, C. M. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109701 · Cited by 60
Lee, B., Mahmud, I., Pokhrel, R., Murad, R., Yuan, M., Stapleton, S. L., Bettegowda, C., Jallo, G. I., Eberhart, C. G., Garrett, T. J., et al. (2022) · Acta Neuropathologica Communications · doi:10.1186/s40478-022-01326-7 · Cited by 65
Self-citationChen, L., Zhang, W., Chen, D., Yang, Q., Sun, S., Dai, Z., Li, Z., Liang, X., Chen, C., Jiao, Y., et al. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01367-x · Cited by 62
CtBP maintains cancer cell growth and metabolic homeostasis via regulating SIRT4
Wang, L., Zhou, H., Wang, Y., Cui, G., & Di, L.-J. (2015) · Cell Death and Disease · doi:10.1038/cddis.2014.587 · Cited by 62
Modeling Targeted Inhibition of MEK and PI3 Kinase in Human Pancreatic Cancer
Junttila, M. R., Devasthali, V., Cheng, J. H., Castillo, J., Metcalfe, C., Clermont, A. C., Otter, D. D., Chan, E., Bou-Reslan, H., Cao, T. C., et al. (2014) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-14-0030 · Cited by 61
Sato, M., Kawana, K., Adachi, K., Fujimoto, A., Yoshida, M., Nakamura, H., Nishida, H., Inoue, T., Taguchi, A., Takahashi, J., et al. (2016) · Oncotarget · doi:10.18632/oncotarget.8947 · Cited by 63
Regulation of Stem Cell Fate by ROS-mediated Alteration of Metabolism
Ryu, J. M., Lee, H. J., Jung, Y. H., Lee, K. H., Kim, D. I., Kim, J. Y., Ko, S. H., Choi, G. E., Chai, I. I., Song, E. J., et al. (2015) · International Journal of Stem Cells · doi:10.15283/ijsc.2015.8.1.24 · Cited by 62
Tran, T. Q., Gabra, M. B. I., Lowman, X. H., Yang, Y., Reid, M. A., Pan, M., O'Connor, T. R., & Kong, M. (2017) · PLoS Biology · doi:10.1371/journal.pbio.2002810 · Cited by 65
Glucose metabolic phenotype of pancreatic cancer
Chan, A. K. C., Bruce, J. I. E., & Siriwardena, A. K. (2016) · World Journal of Gastroenterology · doi:10.3748/wjg.v22.i12.3471 · Cited by 62
An allosteric PGAM1 inhibitor effectively suppresses pancreatic ductal adenocarcinoma
Wen, C., Huang, K., Jiang, L.-L., Lu, X., Dai, Y., Shi, M.-M., Tang, X.-M., Wang, Q., Zhang, X., Wang, P., et al. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1914557116 · Cited by 61
Self-citationMirzaei, S., Gholami, M. H., Mahabady, M. K., Nabavi, N., Zabolian, A., Banihashemi, S. M., Haddadi, A., Entezari, M., Hushmandi, K., Makvandi, P., et al. (2020) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2020.111077 · Cited by 61
RetractedMetabolic Regulation of Fibroblast Activation and Proliferation during Organ Fibrosis
Wang, S., Liang, Y., & Dai, C. (2022) · Kidney Diseases · doi:10.1159/000522417 · Cited by 60
Role of the tumor microenvironment in cancer hallmarks and targeted therapy (Review)
Naser, R., Fakhoury, I., El‑Fouani, A., Abi‑Habib, R., & El‑Sibai, M. (2022) · International Journal of Oncology · doi:10.3892/ijo.2022.5471 · Cited by 61
Nitric oxide and tumor metabolic reprogramming
Lopez-Sanchez, L. M., Aranda, E., & Rodríguez‐Ariza, A. (2019) · Biochemical Pharmacology · doi:10.1016/j.bcp.2019.113769 · Cited by 63
Overview of Cancer Metabolism and Signaling Transduction
Chae, H., & Hong, S. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms24010012 · Cited by 66
Enhanced Glutaminolysis Drives Hypoxia-Induced Chemoresistance in Pancreatic Cancer
Park, S. J., Yoo, H. C., Ahn, E., Luo, E., Kim, Y., Sung, Y., Yu, Y. C., Kim, K., Min, D. S., Lee, H. S., et al. (2023) · Cancer Research · doi:10.1158/0008-5472.can-22-2045 · Cited by 63
KRAS mutation: The booster of pancreatic ductal adenocarcinoma transformation and progression
Zhang, Z., Zhang, H., Liao, X., & Tsai, H. (2023) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2023.1147676 · Cited by 62
Tang, R., Xu, J., Wang, W., Meng, Q., Shao, C., Zhang, Y., Lei, Y., Zhang, Z.-F., Liu, Y., Du, Q., et al. (2023) · Cell Reports Medicine · doi:10.1016/j.xcrm.2023.101234 · Cited by 68
Metabolic reprogramming: a hallmark of viral oncogenesis
Levy, P. L., & Bartosch, B. (2015) · Oncogene · doi:10.1038/onc.2015.479 · Cited by 62
Matschke, J., Riffkin, H., Klein, D., Handrick, R., Lüdemann, L., Metzen, E., Shlomi, T., Stuschke, M., & Jendrossek, V. (2016) · Antioxidants and Redox Signaling · doi:10.1089/ars.2015.6589 · Cited by 63
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
