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 601–700 of 1,004
Recent Progress in the Discovery of Allosteric Inhibitors of Kidney-Type Glutaminase
Zimmermann, S. C., Duvall, B. R., & Tsukamoto, T. (2018) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.8b00327 · Cited by 59
Impact of Lifestyle Behaviors on Cancer Risk and Prevention
Choi, J.-W., & Hua, T. N. M. (2021) · Journal of Lifestyle Medicine · doi:10.15280/jlm.2021.11.1.1 · Cited by 65
Jain, A., & Bhardwaj, V. (2021) · World Journal of Gastroenterology · doi:10.3748/wjg.v27.i39.6527 · Cited by 64
Wang, M., Zhou, C., Yu, L., Kong, D., Ma, W.-J., Lv, B., Wang, Y., Wu, W.-F., Zhou, M., & Cui, G. (2022) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-022-04341-y · Cited by 60
Targeting of SLC25A22 boosts the immunotherapeutic response in KRAS-mutant colorectal cancer
Zhou, Q., Peng, Y., Ji, F., Chen, H., Kang, W., Chan, L.-S., Gou, H., Lin, Y., Huang, P., Chen, D., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-39571-6 · Cited by 63
Overcoming therapy resistance in pancreatic cancer: New insights and future directions
Espona‐Fiedler, M., Patthey, C., Lindblad, S., Sarró, I., & Öhlund, D. (2024) · Biochemical Pharmacology · doi:10.1016/j.bcp.2024.116492 · Cited by 62
Corbet, C., & Féron, O. (2015) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/mco.0000000000000178 · Cited by 61
Functional genomic screening reveals asparagine dependence as a metabolic vulnerability in sarcoma
Hettmer, S., Schinzel, A. C., Tchessalova, D., Schneider, M., Parker, C. L., Bronson, R. T., Richards, N. G. J., Hahn, W. C., & Wagers, A. J. (2015) · eLife · doi:10.7554/elife.09436 · Cited by 60
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
Knudsen, E. S., Balaji, U., Freinkman, E., McCue, P. A., & Witkiewicz, A. K. (2016) · Oncotarget · doi:10.18632/oncotarget.11893 · Cited by 61
Epigenetic silencing of microRNA-137 enhances ASCT2 expression and tumor glutamine metabolism
Dong, J., Xiao, D., Zhao, Z., Ren, P., Li, C., Hu, Y., Shi, J., Su, H., Wang, L., Liu, H., et al. (2017) · Oncogenesis · doi:10.1038/oncsis.2017.59 · Cited by 61
The Role of Mitochondria in the Chemoresistance of Pancreatic Cancer Cells
Fu, Y., Ricciardiello, F., Yang, G., Qiu, J., Huang, H., Xiao, J., Cao, Z., Zhao, F., Liu, Y., Luo, W., et al. (2021) · Cells · doi:10.3390/cells10030497 · Cited by 59
Luan, Z., He, Y., Alattar, M., Chen, Z., & He, F. (2014) · Molecular Cancer · doi:10.1186/1476-4598-13-38 · Cited by 58
Tumorigenicity of hypoxic respiring cancer cells revealed by a hypoxia–cell cycle dual reporter
Le, A., Stine, Z. E., Nguyen, C. C., Afzal, J. M., Sun, P., Hamaker, M. C., Siegel, N. M., Gouw, A. M., Kang, B.-H., Yu, S.-H., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1402012111 · Cited by 61
Challapalli, A., & Aboagye, E. O. (2016) · Frontiers in Oncology · doi:10.3389/fonc.2016.00044 · Cited by 58
Zhang, H., Wang, M.-D., Zhou, X., Qin, C., Fu, G., Tang, L., Wu, H., Huang, S., Zhao, L., Zeng, M., et al. (2016) · Cancer Letters · doi:10.1016/j.canlet.2016.11.023 · Cited by 58
Sun, W., Luan, S., Qi, C., Tong, Q., Yan, S., Li, H., & Zhang, Y. (2019) · Cell Communication and Signaling · doi:10.1186/s12964-019-0425-4 · Cited by 59
Severe metabolic alterations in liver cancer lead to ERK pathway activation and drug resistance
Nwosu, Z. C., Piorońska, W., Battello, N., Zimmer, A. D., Dewidar, B., Han, M., Pereira, S., Blagojevic, B., Castven, D., Charlestin, V., et al. (2020) · EBioMedicine · doi:10.1016/j.ebiom.2020.102699 · Cited by 61
Self-citationMitochondria orchestrate macrophage effector functions in atherosclerosis
Dumont, A., Lee, M., Barouillet, T., Murphy, A. J., & Yvan‐Charvet, L. (2020) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2020.100922 · Cited by 60
Oncology Therapeutics Targeting the Metabolism of Amino Acids
Muhammad, N., Lee, H. M., & Kim, J. (2020) · Cells · doi:10.3390/cells9081904 · Cited by 59
Connections between metabolism and epigenetics: mechanisms and novel anti-cancer strategy
Chen, C., Wang, Z., & Qin, Y. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.935536 · Cited by 62
A Cancer Cell–Intrinsic GOT2–PPARδ Axis Suppresses Antitumor Immunity
Abrego, J., Sanford-Crane, H. S., Oon, C. H., Xu, X., Betts, C. B., Sun, D., Nagarajan, S., Diaz, L. F., Sandborg, H., Bhattacharyya, S., et al. (2022) · Cancer Discovery · doi:10.1158/2159-8290.cd-22-0661 · Cited by 61
Tumor lactic acid: a potential target for cancer therapy
Byun, J. (2023) · Archives of Pharmacal Research · doi:10.1007/s12272-023-01431-8 · Cited by 58
Functions and mechanisms of lactylation in carcinogenesis and immunosuppression
Su, J., Zheng, Z., Bian, C., Chang, S., Bao, J., Yu, H., Xin, Y., & Jiang, X. M. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1253064 · Cited by 57
Role of PKM2 in directing the metabolic fate of glucose in cancer: a potential therapeutic target
van Niekerk, G., & Engelbrecht, A. (2018) · Cellular Oncology · doi:10.1007/s13402-018-0383-7 · Cited by 60
Phospholipase D–dependent mTOR complex 1 (mTORC1) activation by glutamine
Bernfeld, E., Menon, D., Vaghela, V., Zerin, I., Faruque, P. R., Frías, M. A., & Foster, D. A. (2018) · Journal of Biological Chemistry · doi:10.1074/jbc.ra118.004972 · Cited by 57
ME1 promotes basal-like breast cancer progression and associates with poor prognosis
Liao, R., Ren, G., Liu, H., Chen, X., Cao, Q., Wu, X., Li, J., & Dong, C. (2018) · Scientific Reports · doi:10.1038/s41598-018-35106-y · Cited by 59
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
Riedl, J. M., Posch, F., Prager, G. W., Eisterer, W., Oehler, L., Sliwa, T., Wilthoner, K., Petzer, A. L., Pichler, P., Hubmann, E., et al. (2020) · Therapeutic Advances in Medical Oncology · doi:10.1177/1758835919900872 · Cited by 59
Glutamine metabolism in Th17/Treg cell fate: applications in Th17 cell-associated diseases
Yang, G., Xia, Y., & Ren, W. (2020) · Science China Life Sciences · doi:10.1007/s11427-020-1703-2 · Cited by 55
Rational design of ASCT2 inhibitors using an integrated experimental-computational approach
Garibsingh, R. A., Ndaru, E., Garaeva, A. A., Shi, Y., Zielewicz, L. J., Zakrepine, P., Bonomi, M., Slotboom, D. J., Paulino, C., Grewer, C. T., et al. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2104093118 · Cited by 55
Opportunities for Therapeutic Modulation of O-GlcNAc
Cheng, S. S., Mody, A. C., & Woo, C. M. (2024) · Chemical Reviews · doi:10.1021/acs.chemrev.4c00417 · Cited by 64
Metabolism and epigenetics of pancreatic cancer stem cells
Lanfranca, M. P., Thompson, J. K., Bednar, F., Halbrook, C. J., Lyssiotis, C. A., Lévi, B., & Frankel, T. L. (2018) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2018.09.008 · Cited by 58
Self-citationInhibiting both proline biosynthesis and lipogenesis synergistically suppresses tumor growth
Liu, M., Wang, Y., Yang, C., Ruan, Y., Bai, C., Chu, Q., Cui, Y., Chen, C., Ying, G., & Li, B. (2020) · The Journal of Experimental Medicine · doi:10.1084/jem.20191226 · Cited by 57
Metabolomics profile in gastrointestinal cancers: Update and future perspectives
Nannini, G., Meoni, G., Amedei, A., & Tenori, L. (2020) · World Journal of Gastroenterology · doi:10.3748/wjg.v26.i20.2514 · Cited by 58
Targeting mTORC2/HDAC3 Inhibits Stemness of Liver Cancer Cells Against Glutamine Starvation
Zhang, H., Chen, P., Yan, H., Fu, G., Luo, F., Zhang, J., Zhao, S., Zhai, B., Yu, J., Chen, L., et al. (2022) · Advanced Science · doi:10.1002/advs.202103887 · Cited by 54
The interactive role of inflammatory mediators and metabolic reprogramming in pancreatic cancer
Ohara, Y., Valenzuela, P., & Hussain, S. P. (2022) · Trends in cancer · doi:10.1016/j.trecan.2022.03.004 · Cited by 54
Targeting tumour-reprogrammed myeloid cells: the new battleground in cancer immunotherapy
Sanctis, F. D., Adamo, A., Canè, S., & Ugel, S. (2022) · Seminars in Immunopathology · doi:10.1007/s00281-022-00965-1 · Cited by 54
Shimizu, K. (2015) · Advances in biochemical engineering, biotechnology · doi:10.1007/10_2015_320 · Cited by 54
Metabolic circuits in neural stem cells
Kim, D., Rhee, I., & Paik, J. (2014) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-014-1686-0 · Cited by 59
13C Isotope-Assisted Methods for Quantifying Glutamine Metabolism in Cancer Cells
Zhang, J., Ahn, W. S., Gameiro, P. A., Keibler, M. A., Zhang, Z., & Stephanopoulos, G. N. (2014) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/b978-0-12-416618-9.00019-4 · Cited by 55
Abbruzzese, J. L., Andersen, D. K., Borrebaeck, C. A. K., Chari, S. T., Costello, E., Cruz‐Monserrate, Z., Eibl, G., Engleman, E. G., Fisher, W. E., Habtezion, A., et al. (2018) · Pancreas · doi:10.1097/mpa.0000000000001037 · Cited by 57
Self-citationCai, W.-F., Zhang, C., Wu, Y.-Q., 庄桂, Ye, Z., Zhang, C., & Lin, S. (2018) · Cell Research · doi:10.1038/s41422-018-0057-z · Cited by 54
Role of Reductive versus Oxidative Stress in Tumor Progression and Anticancer Drug Resistance
Chun, K., Kim, D., & Surh, Y. (2021) · Cells · doi:10.3390/cells10040758 · Cited by 56
Oncogenes and Tumor Suppressors Regulate Glutamine Metabolism in Cancer Cells
Kim, M., & Kim, H. (2013) · Journal of Cancer Prevention · doi:10.15430/jcp.2013.18.3.221 · Cited by 54
Gong, J., Kelekar, G., Shen, J., Shen, J., Kaur, S., & Mita, M. M. (2016) · Targeted Oncology · doi:10.1007/s11523-016-0423-z · Cited by 56
Kovalenko, I., Glasauer, A., Schöckel, L., Sauter, D. R. P., Ehrmann, A., Sohler, F., Hägebarth, A., Novak, I., & Christian, S. (2016) · PLoS ONE · doi:10.1371/journal.pone.0160658 · Cited by 56
PIK3CA mutant tumors depend on oxoglutarate dehydrogenase
Ilić, N., Birsoy, K., Aguirre, A. J., Kory, N., Pacold, M. E., Singh, S., Moody, S. E., DeAngelo, J. D., Spardy, N. A., Freinkman, E., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1617922114 · Cited by 55
Self-citationChakravarthy, D., Muñoz, A. R., Su, A., Hwang, R. F., Keppler, B. R., Chan, D. E., Halff, G. A., Ghosh, R., & Kumar, A. P. (2018) · Cancer Letters · doi:10.1016/j.canlet.2018.01.057 · Cited by 55
LncRNA XLOC_006390 promotes pancreatic carcinogenesis and glutamate metabolism by stabilizing c-Myc
He, J., Li, F., Zhou, Y., Hou, X., Liu, S., Li, X., Zhang, Y., Jing, X., & Yang, L. (2019) · Cancer Letters · doi:10.1016/j.canlet.2019.11.021 · Cited by 54
Pancreatic Cancer and Its Microenvironment—Recent Advances and Current Controversies
Stopa, K. B., Kusiak, A. A., Szopa, M. D., Ferdek, P. E., & Jakubowska, M. A. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21093218 · Cited by 55
Genipin, an Inhibitor of UCP2 as a Promising New Anticancer Agent: A Review of the Literature
Cho, Y. S. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23105637 · Cited by 55
The Tricarboxylic Acid Cycle Metabolites for Cancer: Friend or Enemy
Wu, J., Liu, N., Chen, J., Tao, Q., Li, Q., Li, J., Chen, X., & Peng, C. (2024) · Research · doi:10.34133/research.0351 · Cited by 57
Time and Circumstances: Cancer Cell Metabolism at Various Stages of Disease Progression
Weber, G. F. (2016) · Frontiers in Oncology · doi:10.3389/fonc.2016.00257 · Cited by 56
Molecular Pathways Controlling Autophagy in Pancreatic Cancer
New, M. I., Acker, T. V., Long, J. S., Sakamaki, J.-I., Ryan, K. M., & Tooze, S. A. (2017) · Frontiers in Oncology · doi:10.3389/fonc.2017.00028 · Cited by 56
MicroRNA-30a attenuates mutant KRAS-driven colorectal tumorigenesis via direct suppression of ME1
Shen, H., Xing, C., Cui, K., Li, Y., Zhang, J., Du, R., Zhang, X., & Li, Y. (2017) · Cell Death and Differentiation · doi:10.1038/cdd.2017.63 · Cited by 53
Kshattry, S., Saha, A., Gries, P., Tiziani, S., Stone, E. M., Georgiou, G., & DiGiovanni, J. (2019) · npj Precision Oncology · doi:10.1038/s41698-019-0088-z · Cited by 54
Yoshida, T., Yamasaki, S., Kaneko, O., Taoka, N., Tomimoto, Y., Namatame, I., Yahata, T., Kuromitsu, S., Cantley, L. C., & Lyssiotis, C. A. (2019) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2019.11.130 · Cited by 53
Self-citationRegulation of mitochondrial plasticity by the i-AAA protease YME1L
Ohba, Y., MacVicar, T., & Langer, T. (2020) · Biological Chemistry · doi:10.1515/hsz-2020-0120 · Cited by 54
Shedding New Light on Cancer Metabolism: A Metabolic Tightrope Between Life and Death
Läsche, M., Emons, G., & Gründker, C. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.00409 · Cited by 55
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
Glutamine Metabolism in Cancer Stem Cells: A Complex Liaison in the Tumor Microenvironment
Pacifico, F., Leonardi, A., & Crescenzi, E. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24032337 · Cited by 53
Rethinking glutamine metabolism and the regulation of glutamine addiction by oncogenes in cancer
Ni, R., Li, Z., Li, L., Peng, D., Ming, Y., Li, L., & Liu, Y. (2023) · Frontiers in Oncology · doi:10.3389/fonc.2023.1143798 · Cited by 57
Association of distinct microbial signatures with premalignant colorectal adenomas
Lee, J. W. J., Plichta, D. R., Asher, S., DelSignore, M., Jeong, T., McGoldrick, J., Staller, K. D., Khalili, H., Xavier, R. J., & Chung, D. C. (2023) · Cell Host & Microbe · doi:10.1016/j.chom.2023.04.007 · Cited by 59
AMPK targets PDZD8 to trigger carbon source shift from glucose to glutamine
Li, M., Wang, Y., Wei, X., Cai, W.-F., Wu, J., Zhu, M., Wang, Y., Liu, Y., Xiong, J., Qu, Q., et al. (2024) · Cell Research · doi:10.1038/s41422-024-00985-6 · Cited by 52
Cyclic fasting-mimicking diet in cancer treatment: Preclinical and clinical evidence
Vernieri, C., Ligorio, F., Tripathy, D., & Longo, V. D. (2024) · Cell Metabolism · doi:10.1016/j.cmet.2024.06.014 · Cited by 57
Molecular Pathways: Targeting the Dependence of Mutant RAS Cancers on the DNA Damage Response
Grabocka, E., Commisso, C., & Bar‐Sagi, D. (2014) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-14-0650 · Cited by 53
Distinct Metabolomic Profiles of Papillary Thyroid Carcinoma and Benign Thyroid Adenoma
Xu, Y., Zheng, X., Qiu, Y., Jia, W. P., Wang, J., & Yin, S. (2015) · Journal of Proteome Research · doi:10.1021/acs.jproteome.5b00351 · Cited by 54
Auslander, N., Cunningham, C. E., Toosi, B. M., McEwen, E., Yizhak, K., Vizeacoumar, F. S., Parameswaran, S., Gonen, N., Freywald, T., Bhanumathy, K. K., et al. (2017) · Molecular Systems Biology · doi:10.15252/msb.20177739 · Cited by 51
RAS signalling in energy metabolism and rare human diseases
Dard, L., Bellancé, N., Lacombe, D., & Rossignol, R. (2018) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2018.05.003 · Cited by 56
Feist, M., Schwarzfischer, P., Heinrich, P., Sun, X., Kemper, J., von Bonin, F., Pérez-Rubio, P., Taruttis, F., Rehberg, T., Dettmer, K., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-03803-x · Cited by 55
Glutamine metabolism in cancer therapy
Nguyen, T.-L., & Durán, R. V. (2018) · Cancer Drug Resistance · doi:10.20517/cdr.2018.08 · Cited by 56
Meijer, T. W. H., Peeters, W. J. M., Dubois, L. J., van Gisbergen, M. W., Biemans, R., Venhuizen, J., Span, P. N., & Bussink, J. (2018) · Lung Cancer · doi:10.1016/j.lungcan.2018.10.016 · Cited by 52
Current State of “Omics” Biomarkers in Pancreatic Cancer
Turanlı, B., Yildirim, E., Gülfidan, G., Arğa, K. Y., & Sinha, R. (2021) · Journal of Personalized Medicine · doi:10.3390/jpm11020127 · Cited by 52
REDD1 loss reprograms lipid metabolism to drive progression of RAS mutant tumorsPreprint
Qiao, S., Koh, S., Vivekanandan, V., Salunke, D., Patra, K. C., Zaganjor, E., Ross, K. N., Mizukami, Y., Jeanfavre, S., Chen, A. L., et al. (2020) · Genes & Development · doi:10.1101/gad.335166.119 · Cited by 52
Self-citationAhmad, R. S., Eubank, T. D., Łukomski, S., & Boone, B. A. (2021) · Biomolecules · doi:10.3390/biom11060901 · Cited by 53
The role of metabolic reprogramming in pancreatic cancer chemoresistance
Liu, C., Li, C., & Liu, Y. (2023) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.1108776 · Cited by 51
Nakashima, C., Yamamoto, K., Fujiwara‐Tani, R., Luo, Y., Matsushima, S., Fujii, K., Ohmori, H., Sasahira, T., Sasaki, T., Kitadai, Y., et al. (2018) · Cancer Science · doi:10.1111/cas.13594 · Cited by 51
Autophagic reliance promotes metabolic reprogramming in oncogenic KRAS-driven tumorigenesis
Lin, H., Chung, Y., Cheng, C.-T., Ouyang, C., Fu, Y., Kuo, C., Chi, K. K., Sadeghi, M., Chu, P. G., Kung, H.-J., et al. (2018) · Autophagy · doi:10.1080/15548627.2018.1450708 · Cited by 53
Discovery and development of small molecule modulators targeting glutamine metabolism
Li, L., Meng, Y., Li, Z., Dai, W., Xu, X. J., Xiao-ling, B., & Bian, J. (2018) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2018.11.066 · Cited by 50
Ferino, A., Rapozzi, V., & Xodo, L. E. (2019) · Journal of Photochemistry and Photobiology B Biology · doi:10.1016/j.jphotobiol.2019.111672 · Cited by 51
3-Phosphoglycerate dehydrogenase: a potential target for cancer treatment
Li, M., Wu, C., Yang, Y., Zheng, M., Yu, S., Wang, J., Chen, L., & Li, H. (2021) · Cellular Oncology · doi:10.1007/s13402-021-00599-9 · Cited by 51
Naik, R., Ban, H. S., Jang, K., Kim, I., Xu, X., Harmalkar, D. S., Shin, S.-A., Kim, M., Kim, B., Park, J., et al. (2017) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.7b01231 · Cited by 50
Huo, J., Wu, L., & Zang, Y. (2020) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.16181 · Cited by 49
Cancer cachexia: lessons from Drosophila
Liu, Y., Saavedra, P. H. V., & Perrimon, N. (2022) · Disease Models & Mechanisms · doi:10.1242/dmm.049298 · Cited by 44
Role of the Tumor Microenvironment in Regulating Pancreatic Cancer Therapy Resistance
Deng, D., Patel, R. H., Chiang, C.-Y., & Hou, P. (2022) · Cells · doi:10.3390/cells11192952 · Cited by 53
Lysosome inhibition sensitizes pancreatic cancer to replication stress by aspartate depletion
Elliott, I. A., Dann, A. M., Xu, S., Kim, S. S., Abt, E. R., Kim, W., Poddar, S., Moore, A. M., Zhou, L., Williams, J. L., et al. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1812410116 · Cited by 54
Immunometabolism: A new target for improving cancer immunotherapy
Guo, C., Chen, S., Liu, W., Ma, Y., Li, J., Fisher, P. B., Fang, X., & Wang, X. (2019) · Advances in cancer research · doi:10.1016/bs.acr.2019.03.004 · Cited by 56
Self-citationTissue 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
Self-citationBharadwaj, S., Singh, M. V., Kirtipal, N., & Kang, S. G. (2021) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2020.627842 · Cited by 50
Tumor Cells and Cancer-Associated Fibroblasts: An Updated Metabolic Perspective
Gentric, G., & Mechta‐Grigoriou, F. (2021) · Cancers · doi:10.3390/cancers13030399 · Cited by 52
Combined blockade of EGFR and glutamine metabolism in preclinical models of colorectal cancer
Cohen, A. S., Geng, L., Zhao, P., Fu, A., Schulte, M. L., Graves-Deal, R., Washington, M. K., Berlin, J., Coffey, R. J., & Manning, H. C. (2020) · Translational Oncology · doi:10.1016/j.tranon.2020.100828 · Cited by 49
Li, J., Song, P., Zhu, L., Aziz, N., Zhou, Q., Zhang, Y., Xu, W., Feng, L., Chen, D., Wang, X., et al. (2017) · Oncotarget · doi:10.18632/oncotarget.16844 · Cited by 46
Self-citationTransporters at the Interface between Cytosolic and Mitochondrial Amino Acid Metabolism
Hewton, K. G., Johal, A. S., & Parker, S. J. (2021) · Metabolites · doi:10.3390/metabo11020112 · Cited by 52
Daniel, Y., Lelou, E., Aninat, C., Corlu, A., & Cabillic, F. (2021) · Cancers · doi:10.3390/cancers13081973 · Cited by 52
The role of branched chain amino acids metabolic disorders in tumorigenesis and progression
Wang, J., Wang, W., Zhu, F., & Duan, Q. (2022) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2022.113390 · Cited by 47
Regulation of Autophagy via Carbohydrate and Lipid Metabolism in Cancer
Alizadeh, J., Kavoosi, M., Singh, N., Lorzadeh, S., Ravandi, A., Kidane, B., Ahmed, N., Mraiche, F., Mowat, M. R. A., & Ghavami, S. (2023) · Cancers · doi:10.3390/cancers15082195 · Cited by 51
Liu, C., Wu, X., Bing, X., Qi, W., Zhu, F., Guo, N., Li, C., Gao, X., Cao, X., Zhao, M., et al. (2023) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2023.05.004 · Cited by 50
The immunometabolic ecosystem in cancer
Bantug, G. R., & Hess, C. (2023) · Nature Immunology · doi:10.1038/s41590-023-01675-y · Cited by 53
Metabolic Phenotypes in Pancreatic Cancer
Yu, M., Zhou, Q., Zhou, Y., Fu, Z., Tan, L., Ye, X., Zeng, B., Gao, W., Zhou, J., Liu, Y., et al. (2015) · PLoS ONE · doi:10.1371/journal.pone.0115153 · Cited by 49
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
