Analysis of glutamine dependency in non-small cell lung cancer: GLS1 splice variant GAC is essential for cancer cell growth
Open accessAbstract
One of the hallmarks of cancer is metabolic deregulation. Many tumors display increased glucose uptake and breakdown through the process of aerobic glycolysis, also known as the Warburg effect. Less studied in cancer development and progression is the importance of the glutamine (Gln) pathway, which provides cells with a variety of essential products to sustain cell proliferation, such as ATP and macromolecules for biosynthesis. To this end Gln dependency was assessed in a panel of non-small cell lung cancer lines (NSCLC). Gln was found to be essential for the growth of cells with high rates of glutaminolysis, and after exploring multiple genes in the Gln pathway, GLS1 was found to be the key enzyme associated with this dependence. This dependence was confirmed by observing the rescue of decreased growth by exogenous addition of downstream metabolites of glutaminolysis. Expression of the GLS1 splice variant KGA was found to be decreased in tumors compared with normal lung tissue. Transient knock down of GLS1 splice variants indicated that loss of GAC had the most detrimental effect on cancer cell growth. In conclusion, NSCLC cell lines depend on Gln for glutaminolysis to a varying degree, in which the GLS1 splice variant GAC plays an essential role and is a potential target for cancer metabolism-directed therapy.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
CB-839 sensitivity has been reported to correlate to a number of functional measures including glutaminase activity, the ratio of intracellular glutamate to glutamine, and the extent to which treatment promoted accumulation of cellular glutamine or depletion of cellular glutamate.
“CB-839 sensitivity has been reported to correlate to a number of functional measures including glutaminase activity, the ratio of intracellular glutamate to glutamine, and the extent to which treatment promoted accumulation of cellular glutamine or depletion of cellular glutamate [19].”
From Combined blockade of EGFR and glutamine metabolism in preclinical models of colorectal cancer (2020) · cites this paper as [19]
The NSCLC cell-line results report that glutamine consumption correlates with glutamine dependency, and the GLS1-inhibition results compare growth responses to BPTES. They do not report CB-839 sensitivity or correlations with glutaminase activity, an intracellular glutamate-to-glutamine ratio, or treatment-induced intracellular metabolite changes. The amino-acid analysis measures glutamine and glutamate in conditioned media, not inside cells (page numbers unavailable in our copy). (LLM, conf=0.85)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Jemal, A., Siegel, R., Ward, E., Hao, Y., Xu, J., & Thun, M. J. (2009) · CA: A Cancer Journal for Clinicians · doi:10.3322/caac.20006 · Cited by 9,709 · see citing works
Gao, P., Tchernyshyov, I., Chang, T.-C., Lee, Y.-S., Kita, K., Ochi, T., Zeller, K. I., De Marzo, A. M., Van Eyk, J. E., Mendell, J. T., et al. (2009) · Nature · doi:10.1038/nature07823 · Cited by 2,124 · see citing works
Wise, 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 · see citing works
Mitochondrial metabolism and ROS generation are essential for Kras-mediated tumorigenicity
Weinberg, F., Hamanaka, R., Wheaton, W. W., Weinberg, S., Joseph, J., Lopez, M., Kalyanaraman, B., Mutlu, G. M., Budinger, G. R. S., & Chandel, N. S. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1003428107 · Cited by 1,742 · see citing works
Q's next: the diverse functions of glutamine in metabolism, cell biology and cancer
DeBerardinis, R. J., & Cheng, T. (2010) · Oncogene · doi:10.1038/onc.2009.358 · Cited by 1,365 · see citing works
Targeting metabolic transformation for cancer therapy
Tennant, D. A., Durán, R. V., & Gottlieb, E. (2010) · Nature reviews. Cancer · doi:10.1038/nrc2817 · Cited by 1,057 · see citing works
Targeting Mitochondrial Glutaminase Activity Inhibits Oncogenic Transformation
Wang, J.-B., Erickson, J. W., Fuji, R., Ramachandran, S., Gao, P., Dinavahi, R., Wilson, K. F., Ambrosio, A. L. B., Dias, S. M. G., Dang, C. V., et al. (2010) · Cancer Cell · doi:10.1016/j.ccr.2010.08.009 · Cited by 821 · see citing works
Pyruvate kinase type M2: A key regulator of the metabolic budget system in tumor cells
Mazurek, S. (2011) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2010.02.005 · Cited by 694 · see citing works
Inhibition of Glutaminase Preferentially Slows Growth of Glioma Cells with Mutant IDH1
Seltzer, M. J., Bennett, B. D., Joshi, A. D., Gao, P., Thomas, A. G., Ferraris, D. V., Tsukamoto, T., Rojas, C. J., Slusher, B. S., Rabinowitz, J. D., et al. (2010) · Cancer Research · doi:10.1158/0008-5472.can-10-1666 · Cited by 513 · see citing works
Robinson, M. M., McBryant, S. J., Tsukamoto, T., Rojas, C. J., Ferraris, D. V., Hamilton, S. K., Hansen, J. C., & Curthoys, N. P. (2007) · Biochemical Journal · doi:10.1042/bj20070039 · Cited by 344 · see citing works
Matés, J. M., Pérez‐Gómez, C., de Castro, I. N., Asenjo, M., & Márquez, J. (2002) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/s1357-2725(01)00143-1 · Cited by 340 · see citing works
Gene expression profiling reveals novel biomarkers in nonsmall cell lung cancer
Sánchez‐Palencia, A., Gómez‐Morales, M., Gómez‐Capilla, J. A., Pedraza, V., Boyero, L., Rosell, R., & Fárez‐Vidal, M. E. (2010) · International Journal of Cancer · doi:10.1002/ijc.25704 · Cited by 287 · see citing works
Cassago, A., Ferreira, A. P. S., Ferreira, I. M., Fornezari, C., Gomes, E. R. M., Greene, K. S., Pereira, H. M., Garratt, R. C., Dias, S. M. G., & Ambrosio, A. L. B. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1112495109 · Cited by 287 · see citing works
The role of glutathione in brain tumor drug resistance
Backos, D. S., Franklin, C. C., & Reigan, P. (2011) · Biochemical Pharmacology · doi:10.1016/j.bcp.2011.11.016 · Cited by 196 · see citing works
Elgadi, K. M., Meguid, R. A., Qian, M. D., Souba, W. W., & Abcouwer, S. F. (1999) · Physiological Genomics · doi:10.1152/physiolgenomics.1999.1.2.51 · Cited by 195 · see citing works
LOBO, C., RUIZ-BELLIDO, M. A., ALEDO, J. C., MÁRQUEZ, J., NÚÑEZ DE CASTRO, I., & ALONSO, F. J. (2000) · Biochemical Journal · doi:10.1042/bj3480257 · Cited by 151 · see citing works
Sandulache, V. C., Ow, T. J., Pickering, C. R., Frederick, M. J., Zhou, G., Fokt, I., Davis‐Malesevich, M., Priebe, W., & Myers, J. N. (2011) · Cancer · doi:10.1002/cncr.25868 · Cited by 143 · see citing works
Lora, J., Alonso, F. J., Segura, J. A., Lobo, C., Márquez, J., & Matés, J. M. (2004) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.2004.04370.x · Cited by 134 · see citing works
Molecular Target Class Is Predictive of In vitro Response Profile
Greshock, J. D., Bachman, K. E., Degenhardt, Y., Jing, J., Wen, Y. H., Eastman, S. D., McNeil, E., Moy, C. H., Wegrzyn, R. J., Auger, K. R., et al. (2010) · Cancer Research · doi:10.1158/0008-5472.can-09-3788 · Cited by 124 · see citing works
Self-citationPremature senescence of human endothelial cells induced by inhibition of glutaminase
Unterluggauer, H., Mazurek, S., Lener, B., Hütter, E., EIGENBRODT, E., Zwerschke, W., & Jansen‐Dürr, P. (2008) · Biogerontology · doi:10.1007/s10522-008-9134-x · Cited by 107 · see citing works
Pinkus, L. M. (1977) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(77)46049-x · Cited by 89 · see citing works
Nitrogen anabolism underlies the importance of glutaminolysis in proliferating cells
Meng, M., Chen, S., Lao, T., Liang, D., & Sang, N. (2010) · Cell Cycle · doi:10.4161/cc.9.19.13139 · Cited by 86 · see citing works
Glutamine in neoplastic cells: Focus on the expression and roles of glutaminases
Szeliga, M., & Obara-Michlewska, M. (2009) · Neurochemistry International · doi:10.1016/j.neuint.2009.01.008 · Cited by 76 · see citing works
Complexity and species variation of the kidney-type glutaminase gene
Porter, L. D., Ibrahim, H., Taylor, L. E., & Curthoys, N. P. (2002) · Physiological Genomics · doi:10.1152/physiolgenomics.00017.2002 · Cited by 74 · see citing works
Relative Expression of mRNAS Coding for Glutaminase Isoforms in CNS Tissues and CNS Tumors
Szeliga, M., Matyja, E., Obara‐Michlewska, M., Grajkowska, W., Czernicki, T., & Albrecht, J. (2007) · Neurochemical Research · doi:10.1007/s11064-007-9507-6 · Cited by 50 · see citing works
Adaptive Alterations in Cellular Metabolism With Malignant Transformation
Fischer, C. P., Bode, B. P., & Souba, W. W. (1998) · Annals of Surgery · doi:10.1097/00000658-199805000-00003 · Cited by 27 · see citing works
Perera, S. Y., Chen, T. C., & Curthoys, N. P. (1990) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)38229-2 · Cited by 24 · see citing works
Wu, F., Lukinius, A., Bergström, M., Eriksson, B. K., Watanabe, Y., & Långström, B. (1999) · European Journal of Cancer · doi:10.1016/s0959-8049(99)00099-4 · Cited by 22 · see citing works
Glutamine antagonist with diet deficient in glutamine and aspartate reduce tumor growth.
Yoshioka, K., Takehara, H., Okada, A., & Komi, N. (1992) · PubMed · Cited by 9 · see citing works
Kinetics of a Novel Isoform of Phosphate Activated Glutaminase (PAG) in SH-SY5Y Neuroblastoma Cells
Roberg, B., Torgner, I. A., & Kvamme, E. (2009) · Neurochemical Research · doi:10.1007/s11064-009-0077-7 · Cited by 8 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
From Krebs to clinic: glutamine metabolism to cancer therapy
Altman, B. J., Stine, Z. E., & Dang, C. V. (2016) · Nature Reviews Cancer · doi:10.1038/nrc.2016.71 · Cited by 2,119 · see citing works
Glutamine and cancer: cell biology, physiology, and clinical opportunities
Hensley, C. T., Wasti, A. T., & DeBerardinis, R. J. (2013) · Journal of Clinical Investigation · doi:10.1172/jci69600 · Cited by 1,262 · see citing works
Antitumor activity of the glutaminase inhibitor CB-839 in triple-negative breast cancer
Gross, M. I., Demo, S. D., Dennison, J. B., Chen, L., Chernov-Rogan, T., Goyal, B., Janes, J. R., Laidig, G. J., Lewis, E. R., Li, J., et al. (2014) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-13-0870 · Cited by 1,068 · see citing works
Environment impacts the metabolic dependencies of Ras-driven non-small cell lung cancer
Davidson, S. M., Papagiannakopoulos, T., Olenchock, B. A., Heyman, J. E., Keibler, M. A., Luengo, A., Bauer, M. R., Jha, A. K., O’Brien, J. P., Pierce, K. A., et al. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.01.007 · Cited by 737 · see citing works
MYC, Metabolism, Cell Growth, and TumorigenesisPreprint
Dang, C. V. (2013) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a014217 · Cited by 600 · see citing works
Timmerman, L. A., Holton, T., Yuneva, M., Louie, R. J., Padró, M., Daemen, A., Hu, M., Chan, D. A., Ethier, S. P., van ‘t Veer, L. J., et al. (2013) · Cancer Cell · doi:10.1016/j.ccr.2013.08.020 · Cited by 573 · see citing works
Xia, Z., Donehower, L., Cooper, T., Neilson, J., Wheeler, D., Wagner, E., & Li, W. (2014) · Nature Communications · doi:10.1038/ncomms6274 · Cited by 509 · see citing works
Aberrant RNA splicing in cancer; expression changes and driver mutations of splicing factor genes
Sveen, A., Kilpinen, S. K., Ruusulehto, A., Lothe, R. A., & Skotheim, R. I. (2015) · Oncogene · doi:10.1038/onc.2015.318 · Cited by 463 · see citing works
Vascular stiffness mechanoactivates YAP/TAZ-dependent glutaminolysis to drive pulmonary hypertension
Bertero, T., Oldham, W. M., Cottrill, K. A., Pisano, S., Vanderpool, R. R., Yu, Q., Zhao, J., Tai, Y., Tang, Y., Zhang, Y.-Y., et al. (2016) · Journal of Clinical Investigation · doi:10.1172/jci86387 · Cited by 438 · see citing works
Targeted inhibition of tumor-specific glutaminase diminishes cell-autonomous tumorigenesis
Xiang, Y., Stine, Z. E., Xia, J., Lu, Y., O’Connor, R. S., Altman, B. J., Hsieh, A. L., Gouw, A. M., Thomas, A. G., Gao, P., et al. (2015) · Journal of Clinical Investigation · doi:10.1172/jci75836 · Cited by 409 · see citing works
Energy metabolism in health and diseases
Liu, H., Wang, S., Wang, J., Guo, X., Song, Y., Fu, K., Gao, Z., Liu, D., He, W., & Yang, L. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02141-x · Cited by 438 · see citing works
Jacque, N., Ronchetti, A. M., Larrue, C., Meunier, G., Birsen, R., Willems, L., Saland, E., Decroocq, J., Maciel, T. T., Lambert, M., et al. (2015) · Blood · doi:10.1182/blood-2015-01-621870 · Cited by 387 · see citing works
Endothelial Cell Metabolism in Health and Disease
Rohlenová, K., Veys, K., Santos, I. M., Bock, K. D., & Carmeliet, P. (2017) · Trends in Cell Biology · doi:10.1016/j.tcb.2017.10.010 · Cited by 336 · see citing works
Role of glutamine and interlinked asparagine metabolism in vessel formation
Huang, H., Vandekeere, S., Kalucka, J., Bierhansl, L., Zecchin, A., Brüning, U., Visnagri, A., Yuldasheva, N., Goveia, J., Cruys, B., et al. (2017) · The EMBO Journal · doi:10.15252/embj.201695518 · Cited by 320 · see citing works
The metabolic landscape of RAS-driven cancers from biology to therapy
Mukhopadhyay, S., Vander Heiden, M. G., & McCormick, F. (2021) · Nature Cancer · doi:10.1038/s43018-021-00184-x · Cited by 315 · see citing works
Muir, A., Danai, L. V., Gui, D. Y., Waingarten, C. Y., Lewis, C. A., & Vander Heiden, M. G. (2017) · eLife · doi:10.7554/elife.27713 · Cited by 311 · see citing works
Inhibition of Glycolysis and Glutaminolysis: An Emerging Drug Discovery Approach to Combat Cancer
Akins, N. S., Nielson, T. C., & Le, H. V. (2018) · Current Topics in Medicinal Chemistry · doi:10.2174/1568026618666180523111351 · Cited by 254 · see citing works
Li, B., Cao, Y., Meng, G., Qian, L., Xu, T., Yan, C., Luo, O., Wang, S., Wei, J., Ding, Y., et al. (2019) · EBioMedicine · doi:10.1016/j.ebiom.2018.11.063 · Cited by 245 · see citing works
The Cancer Spliceome: Reprograming of Alternative Splicing in Cancer
Marabti, E. E., & Younis, I. (2018) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2018.00080 · Cited by 217 · see citing works
Unique Metabolic Adaptations Dictate Distal Organ-Specific Metastatic Colonization
Schild, T., Low, V., Blenis, J., & Gomes, A. P. (2018) · Cancer Cell · doi:10.1016/j.ccell.2018.02.001 · Cited by 185 · see citing works
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 · see citing works
Allele-Specific Reprogramming of Cancer Metabolism by the Long Non-coding RNA CCAT2
Redis, R. S., Vela, L. E., Lu, W., de Oliveira, J. F., Ivan, C., Rodriguez‐Aguayo, C., Adamóski, D., Pasculli, B., Taguchi, A., Chen, Y., et al. (2016) · Molecular Cell · doi:10.1016/j.molcel.2016.01.015 · Cited by 182 · see citing works
Wang, 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 184 · see citing works
Targeting Glutamine Metabolism and Redox State for Leukemia Therapy
Gregory, M. A., Nemkov, T. G., Park, H. J., Zaberezhnyy, V., Gehrke, S. A., Adane, B., Jordan, C. T., Hansen, K. C., D’Alessandro, A., & DeGregori, J. V. (2019) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-18-3223 · Cited by 173 · see citing works
The role of glutaminase in cancer
Masisi, B. K., Ansari, R. E., Alfarsi, L. H., Rakha, E. A., Green, A. R., & Craze, M. L. (2019) · Histopathology · doi:10.1111/his.14014 · Cited by 169 · see citing works
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 168 · see citing works
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 166 · see citing works
Therapeutic targeting of glutaminolysis as an essential strategy to combat cancer
Matés, J. M., Paola, F. J. D., Campos-Sandoval, J. A., Mazurek, S., & Márquez, J. (2019) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2019.05.012 · Cited by 164 · see citing works
Rational Cell Culture Optimization Enhances Experimental Reproducibility in Cancer Cells
Wright Muelas, M., Ortega, F., Breitling, R., Bendtsen, C., & Westerhoff, H. V. (2018) · Scientific Reports · doi:10.1038/s41598-018-21050-4 · Cited by 160 · see citing works
Sappington, D. R., Siegel, E. R., Hiatt, G., Desai, A., Penney, R. B., Jamshidi-Parsian, A., Griffin, R. J., & Boysen, G. (2016) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2016.01.021 · Cited by 143 · see citing works
“Therefore, to test whether glutamine as an energy and nutrient source was essential for cell proliferation and a precursor for glutathione synthesis, cells were treated with a specific GLS inhibitor [24,35].”
BackgroundHopefully 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 135 · see citing works
Glutaminase regulation in cancer cells: a druggable chain of events
Katt, W. P., & Cerione, R. A. (2013) · Drug Discovery Today · doi:10.1016/j.drudis.2013.10.008 · Cited by 130 · see citing works
Glutamine Addiction and Therapeutic Strategies in Lung Cancer
Vanhove, K., Derveaux, E., Graulus, G., Mesotten, L., Thomeer, M., Noben, J., Guedens, W., & Adriaensens, P. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20020252 · Cited by 128 · see citing works
Glutaminase inhibitor CB-839 synergizes with carfilzomib in resistant multiple myeloma cells
Thompson, R. M., Dytfeld, D., Reyes, L., Robinson, R. M., Smith, B. M., Manevich, Y., Jakubowiak, A. J., Komarnicki, M. A., Przybyłowicz-Chalecka, A., Szczepaniak, T., et al. (2017) · Oncotarget · doi:10.18632/oncotarget.16262 · Cited by 126 · see citing works
Overview of the Development of Glutaminase Inhibitors: Achievements and Future Directions
Xu, X. J., Meng, Y., Li, L., Xu, P., Wang, J., Li, Z., & Bian, J. (2018) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.8b00961 · Cited by 118 · see citing works
Integration of single-cell RNA-seq data into population models to characterize cancer metabolism
Damiani, C., Maspero, D., Filippo, M. D., Colombo, R., Pescini, D., Graudenzi, A., Westerhoff, H. V., Alberghina, L., Vanoni, M., & Mauri, G. (2019) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1006733 · Cited by 114 · see citing works
Goswami, M. T., Chen, G., Chakravarthi, B. V. S. K., Pathi, S. S., Anand, S. K., Carskadon, S. L., Giordano, T. J., Chinnaiyan, A. M., Thomas, D. G., Palanisamy, N., et al. (2015) · Oncotarget · doi:10.18632/oncotarget.4352 · Cited by 112 · see citing works
Altered Glutamine Metabolism and Therapeutic Opportunities for Lung Cancer
Mohamed, A., Deng, X., Khuri, F. R., & Owonikoko, T. K. (2013) · Clinical Lung Cancer · doi:10.1016/j.cllc.2013.09.001 · Cited by 111 · see citing works
Boysen, G., Jamshidi‐Parsian, A., Davis, M. A., Siegel, E. R., Simecka, C. M., Kore, R. A., Dings, R. P. M., & Griffin, R. J. (2018) · International Journal of Radiation Biology · doi:10.1080/09553002.2018.1558299 · Cited by 107 · see citing works
A review of metabolism-associated biomarkers in lung cancer diagnosis and treatment
Bamji, S. F., van Berkel, V. H., Miller, D. M., & Frieboes, H. B. (2018) · Metabolomics · doi:10.1007/s11306-018-1376-2 · Cited by 97 · see citing works
Saha, S. K., Islam, S. M. R., Abdullah-Al-Wadud, M., Islam, M. S., Ali, F., & Park, K. S. (2019) · Journal of Clinical Medicine · doi:10.3390/jcm8030355 · Cited by 97 · see citing works
Harding, J. J., Telli, M. L., Münster, P. N., Voss, M. H., Infante, J. R., DeMichele, A. M., Dunphy, M. P., Le, M. H., Molineaux, C., Orford, K. W., et al. (2021) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-21-1204 · Cited by 98 · see citing works
Huang, M., Myers, C. R., Wang, Y., & You, M. (2020) · Cancer Prevention Research · doi:10.1158/1940-6207.capr-20-0425 · Cited by 97 · see citing works
Glutamine addiction in tumor cell: oncogene regulation and clinical treatment
Li, X., Peng, X., Li, Y., Wei, S., He, G., Liu, J., Li, X., Yang, S., Dai, L., Lin, W., et al. (2024) · Cell Communication and Signaling · doi:10.1186/s12964-023-01449-x · Cited by 99 · see citing works
Altered glutamine metabolism in platinum resistant ovarian cancer
Hudson, C. D., Savadelis, A., Nagaraj, A. B., Joseph, P. L., Avril, S., DiFeo, A. V., & Avril, N. E. (2016) · Oncotarget · doi:10.18632/oncotarget.9317 · Cited by 95 · see citing works
Daemen, A., Liu, B., Song, K., Kwong, M., Gao, M., Hong, R., Nannini, M., Peterson, D., Liederer, B. M., de la Cruz, C., et al. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.06.003 · Cited by 89 · see citing works
Advancing Cancer Treatment by Targeting Glutamine Metabolism—A Roadmap
Halama, A., & Suhre, K. (2022) · Cancers · doi:10.3390/cancers14030553 · Cited by 92 · see citing works
Alam, M. M., Lal, S., FitzGerald, K. E., & Li, Z. (2016) · Clinical and Translational Medicine · doi:10.1186/s40169-016-0082-9 · Cited by 87 · see citing works
Targeting GLS1 to cancer therapy through glutamine metabolism
Yu, W., Yang, X., Zhang, Q., Sun, L., Yuan, S., & Xin, Y. (2021) · Clinical & Translational Oncology · doi:10.1007/s12094-021-02645-2 · Cited by 86 · see citing works
Stalnecker, C. A., Ulrich, S. M., Li, Y., Ramachandran, S., McBrayer, M. K., DeBerardinis, R. J., Cerione, R. A., & Erickson, J. W. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1414056112 · Cited by 87 · see citing works
Gouda, M. A., Voss, M. H., Tawbi, H. A., Gordon, M. S., Tykodi, S. S., Lam, E. T., Vaishampayan, U. N., Tannir, N. M., Chaves, J. M., Nikolinakos, P. G., et al. (2025) · ESMO Open · doi:10.1016/j.esmoop.2025.104536 · Cited by 86 · see citing works
Upregulated SLC1A5 promotes cell growth and survival in colorectal cancer.
Huang, F., Zhao, Y., Zhao, J., Wu, S., Jiang, Y., Ma, H., & Zhang, T. (2014) · PubMed Central · Cited by 85 · see citing works
Glutamine as an Essential Amino Acid for KRas-Driven Cancer Cells
Bernfeld, E., & Foster, D. A. (2019) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2019.03.003 · Cited by 85 · see citing works
A proposed role for glutamine in cancer cell growth through acid resistance
Huang, W., Choi, W.-Y., Chen, Y., Zhang, Q., Deng, H., He, W. A., & Shi, Y. (2013) · Cell Research · doi:10.1038/cr.2013.15 · Cited by 85 · see citing works
Huang, Q., Stalnecker, C. A., Zhang, C., McDermott, L. A., Iyer, P. C., O’Neill, J., Reimer, S., Cerione, R. A., & Katt, W. P. (2018) · Journal of Biological Chemistry · doi:10.1074/jbc.m117.810101 · Cited by 83 · see citing works
The Ephrin-A1/EPHA2 Signaling Axis Regulates Glutamine Metabolism in HER2-Positive Breast Cancer
Youngblood, V., Kim, L. C., Edwards, D. N., Hwang, Y., Santapuram, P. R., Stirdivant, S. M., Lu, P., Ye, F., Brantley‐Sieders, D. M., & Chen, J. (2016) · Cancer Research · doi:10.1158/0008-5472.can-15-0847 · Cited by 81 · see citing works
Teng, R., Liu, Z., Tang, H., Zhang, W., Chen, Y., Xu, R., Chen, L., Song, J., Liu, X., & Deng, H. (2019) · Redox Biology · doi:10.1016/j.redox.2019.101218 · Cited by 81 · see citing works
Jiang, B., Zhang, J., Zhao, G., Liu, M., Hu, J., Lin, F., Wang, J., Zhao, W., Ma, H., Zhang, C., et al. (2021) · Molecular Cell · doi:10.1016/j.molcel.2022.03.016 · Cited by 81 · see citing works
Amoedo, N. D., Obre, E., & Rossignol, R. (2017) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2017.02.005 · Cited by 76 · see citing works
Amino acid metabolism as a therapeutic target in cancer: a review
Endicott, M., Jones, M. J., & Hull, J. (2021) · Amino Acids · doi:10.1007/s00726-021-03052-1 · Cited by 75 · see citing works
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 73 · see citing works
Fahrmann, J. F., Grapov, D., Wanichthanarak, K., DeFelice, B. C., Salemi, M., Rom, W. N., Gandara, D. R., Phinney, B. S., Fiehn, O., Pass, H. I., et al. (2016) · Carcinogenesis · doi:10.1093/carcin/bgw205 · Cited by 72 · see citing works
Metabolic Reprogramming in Tumor Endothelial Cells
García‐Caballero, M., Sokol, L., Cuypers, A., & Carmeliet, P. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms231911052 · Cited by 71 · see citing works
Leblic, B. C., García‐Barrera, T., Guzmán, J. G., Pereira‐Vega, A., & Gómez‐Ariza, J. L. (2016) · Journal of Proteomics · doi:10.1016/j.jprot.2016.05.030 · Cited by 72 · see citing works
Hoerner, C. R., Chen, V. J., & Fan, A. C. (2019) · Kidney Cancer · doi:10.3233/kca-180043 · Cited by 68 · see citing works
Allosteric Glutaminase Inhibitors Based on a 1,4-Di(5-amino-1,3,4-thiadiazol-2-yl)butane Scaffold
Zimmermann, S. C., Wolf, E. F., Luu, A., Thomas, A. G., Stathis, M. J., Poore, B., Nguyen, C. C., Le, A., Rojas, C. J., Slusher, B. S., et al. (2016) · ACS Medicinal Chemistry Letters · doi:10.1021/acsmedchemlett.6b00060 · Cited by 68 · see citing works
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 · see citing works
Molecular targeting of glutaminase sensitizes ovarian cancer cells to chemotherapy
Masamha, C. P., & LaFontaine, P. R. (2018) · Journal of Cellular Biochemistry · doi:10.1002/jcb.26814 · Cited by 66 · see citing works
Current State of Melanoma Therapy and Next Steps: Battling Therapeutic Resistance
Fateeva, A., Eddy, K., & Chen, S. (2024) · Cancers · doi:10.3390/cancers16081571 · Cited by 64 · see citing works
Sommerkamp, P., Altamura, S., Renders, S., Narr, A., Ladel, L., Zeisberger, P., Eiben, P. L., Fawaz, M., Rieger, M., Cabezas-Wallscheid, N., et al. (2020) · Cell Stem Cell · doi:10.1016/j.stem.2020.03.003 · Cited by 57 · see citing works
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 · see citing works
Han, T., Zhan, W., Gan, M., Liu, F., Yu, B., Chin, Y. E., & Wang, J.-B. (2018) · Cell Research · doi:10.1038/s41422-018-0021-y · Cited by 58 · see citing works
Dual targeting of glutaminase 1 and thymidylate synthase elicits death synergistically in NSCLC
Lee, J.-S., Kang, J. H., Lee, S.-H., Hong, D., Son, J., Hong, K. M., Song, J., & Kim, S.-Y. (2016) · Cell Death & Disease · doi:10.1038/cddis.2016.404 · Cited by 56 · see citing works
Han, T., Guo, M., Zhang, T., Gan, M., Xie, C., & Wang, J.-B. (2016) · Oncotarget · doi:10.18632/oncotarget.14188 · Cited by 55 · see citing works
Tumor metabolic reprogramming in lung cancer progression (Review)
Li, X., Liu, M., Liu, H., & Chen, J. (2022) · Oncology Letters · doi:10.3892/ol.2022.13407 · Cited by 52 · see citing works
Targeting the glutamine-arginine-proline metabolism axis in cancer
Wang, D., Duan, J., Guo, Y., Chen, J., Chen, T.-Q., Wang, J., & Yu, S. (2024) · Journal of Enzyme Inhibition and Medicinal Chemistry · doi:10.1080/14756366.2024.2367129 · Cited by 54 · see citing works
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 · see citing works
Sex differences in brain tumor glutamine metabolism reveal sex-specific vulnerabilities to treatment
Sponagel, J., Jones, J. K., Frankfater, C., Zhang, S., Tung, O., Cho, K., Tinkum, K. L., Gass, H., Núñez, E., Spitz, D. R., et al. (2022) · Med · doi:10.1016/j.medj.2022.08.005 · Cited by 51 · see citing works
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 49 · see citing works
Seyfried, T. N., & Chinopoulos, C. (2021) · Metabolites · doi:10.3390/metabo11090572 · Cited by 52 · see citing works
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 · see citing works
Lu, W.-Q., Hu, Y.-Y., Lin, X.-P., & Fan, W. (2017) · Oncotarget · doi:10.18632/oncotarget.17396 · Cited by 49 · see citing works
Zhang, Z., Li, M., Li, X., Feng, Z., Luo, G., Wang, Y., & Gao, X. (2024) · Journal of Neuroinflammation · doi:10.1186/s12974-024-03254-w · Cited by 53 · see citing works
Nault, R., Fader, K. A., Kirby, M. P., Ahmed, S., Matthews, J. B., Jones, A. D., Lunt, S. Y., & Zacharewski, T. R. (2015) · Toxicological Sciences · doi:10.1093/toxsci/kfv245 · Cited by 49 · see citing works
Wang, C., Wu, J., Wang, Z., Yang, Z., Li, Z., Deng, H., Li, L., Peng, X., & Feng, M. (2018) · Biomaterials · doi:10.1016/j.biomaterials.2018.08.035 · Cited by 49 · see citing works
Grand, M. L., Mukha, A., Püschel, J., Valli, E., Kamili, A., Vittorio, O., Dubrovska, A., & Kavallaris, M. (2020) · Theranostics · doi:10.7150/thno.42602 · Cited by 48 · see citing works
Structural basis for exploring the allosteric inhibition of human kidney type glutaminase
Ramachandran, S., Pan, C. Q., Zimmermann, S. C., Duvall, B. R., Tsukamoto, T., Low, B. C., & Sivaraman, J. (2016) · Oncotarget · doi:10.18632/oncotarget.10791 · Cited by 48 · see citing works
Xie, C., Jin, J., Bao, X., Zhan, W.-H., Han, T.-Y., Gan, M., Zhang, C., & Wang, J. (2016) · Oncotarget · doi:10.18632/oncotarget.6311 · Cited by 47 · see citing works
Ulanet, D., Couto, K., Jha, A., Choe, S. E., Wang, Y., Woo, H.-K., Steadman, M., DeLaBarre, B., Größ, S., Driggers, E. M., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0115144 · Cited by 46 · see citing works
Cheng, Z.-J., Miao, D.-L., Su, Q.-Y., Tang, X.-L., Wang, X.-L., Deng, L.-B., Shi, H., & Xin, H. (2018) · Acta Pharmacologica Sinica · doi:10.1038/s41401-018-0187-3 · Cited by 44 · see citing works
Lou, T., Sethuraman, D., Dospoy, P. D., Srivastva, P., Kim, H. S., Kim, J., Ma, X., Chen, P.-H., Huffman, K. E., Frink, R. E., et al. (2015) · Cancer Prevention Research · doi:10.1158/1940-6207.capr-14-0287 · Cited by 315 · see citing works
Yang, J., Chen, F., Lang, L., Yang, F., Fu, Z., Martínez, J., Cho, A., Saba, N. F., & Teng, Y. (2024) · Cancer Research · doi:10.1158/0008-5472.can-24-0254 · Cited by 43 · see citing works
Sanders, E. B., & Diehl, S. (2015) · Oncoscience · doi:10.18632/oncoscience.128 · Cited by 42 · see citing works
Cetinbas, N. M., Sudderth, J., Harris, R. C., Cebeci, A., Negri, G. L., Yilmaz, Ö. H., DeBerardinis, R. J., & Sorensen, P. H. B. (2016) · Scientific Reports · doi:10.1038/srep32606 · Cited by 42 · see citing works
Glutamine metabolism via glutaminase 1 in autosomal-dominant polycystic kidney disease
Soomro, I., Sun, Y., Zhai, L., Diggs, L., Hatzivassiliou, G., Thomas, A. G., Rais, R., Slusher, B. S., Somlo, S., & Skolnik, E. Y. (2017) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfx349 · Cited by 43 · see citing works
A clinically attainable dose of L‐asparaginase targets glutamine addiction in lymphoid cell lines
Sugimoto, K., Suzuki, H. I., Fujimura, T., Ono, A., Kaga, N., Isobe, Y., Sasaki, M., Taka, H., Miyazono, K., & Komatsu, N. (2015) · Cancer Science · doi:10.1111/cas.12807 · Cited by 42 · see citing works
Guo, L., Zhou, B. O., Liu, Z., Xu, Y., Lü, H., Xia, M., Guo, E., Shan, W., Chen, G., & Wang, C. (2016) · Tumor Biology · doi:10.1007/s13277-016-4984-3 · Cited by 42 · see citing works
Targeting fuel pocket of cancer cell metabolism: A focus on glutaminolysis
Sharma, S., Agnihotri, N., & Kumar, S. (2022) · Biochemical Pharmacology · doi:10.1016/j.bcp.2022.114943 · Cited by 42 · see citing works
Systematic analyses of glutamine and glutamate metabolisms across different cancer types
Tian, Y., Du, W., Cao, S., Wu, Y., Dong, N., Wang, Y., & Xu, Y. (2017) · 癌症：英文版 · doi:10.1186/s40880-017-0255-y · Cited by 41 · see citing works
Fan, Y., Xue, H., Li, Z., Huo, M., Gao, H., & Guan, X. (2024) · Frontiers in Pharmacology · doi:10.3389/fphar.2024.1345522 · Cited by 40 · see citing works
- Authors
- van den Heuvel, A. P. J., Jing, J., Wooster, R. F., & Bachman, K. E.
- Affiliations
- GlaxoSmithKline (United Kingdom) (GB)
- Corresponding author
- Bachman, Kurtis E.
- Venue
- Cancer Biology & Therapy
- Publisher
- Informa UK Limited
- Published
- 2012-10
- Volume
- 13
- Issue
- 12
- Pages
- 1185-1194
- ISSN
- 1538-4047 (ISSN-L)
- 1555-8576
- PMC
- PMC3469476
- OpenAlex
- W1973304708
- Cited by
- 209
- References
- 30
- Citations by year
- 2026: 7 · 2025: 15 · 2024: 14 · 2023: 11 · 2022: 19 · 2021: 15 · 2020: 14 · 2019: 19 · 2018: 25 · 2017: 19 · 2016: 24 · 2015: 15 · 2014: 6 · 2013: 6
- FWCI
- 2.86
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cancer Biology & Therapy (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- GlaxoSmithKline
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biotechnology › Cancer Research and Treatments
- Keywords
- glutamine dependency, non-small cell lung cancer, glutaminolysis, GLS1, cancer metabolism, Warburg effect, aerobic glycolysis, glutamine metabolism
- MeSH terms
- Carcinoma, Non-Small-Cell Lung, Glutaminase, Glutamine, Glycolysis, Humans, Lung Neoplasms, Protein Isoforms, Cell Line, Tumor, Cell Proliferation, Molecular Targeted Therapy
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
