ATF4 Regulates MYC-Mediated Neuroblastoma Cell Death upon Glutamine Deprivation
Open accessAbstract
Oncogenic Myc alters mitochondrial metabolism, making it dependent on exogenous glutamine (Gln) for cell survival. Accordingly, Gln deprivation selectively induces apoptosis in MYC-overexpressing cells via unknown mechanisms. Using MYCN-amplified neuroblastoma as a model, we identify PUMA, NOXA, and TRB3 as executors of Gln-starved cells. Gln depletion in MYC-transformed cells induces apoptosis through ATF4-dependent, but p53-independent, PUMA and NOXA induction. MYC-transformed cells depend on both glutamate-oxaloacetate transaminase and glutamate dehydrogenase to maintain Gln homeostasis and suppress apoptosis. Consequently, either ATF4 agonists or glutaminolysis inhibitors potently induce apoptosis in vitro and inhibit tumor growth in vivo. These results reveal mechanisms whereby Myc sensitizes cells to apoptosis, and validate ATF4 agonists and inhibitors of Gln metabolism as potential Myc-selective cancer therapeutics.
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?
CHK1 inhibitors and glutaminase inhibitors are considered potential candidates for treating Myc-overexpressing cancers.
“Similarly, checkpoint kinase 1 (CHK1) inhibitors625–627 and glutaminase (GLS) inhibitors628–634 are also considered potential candidates for treating Myc-overexpressing cancers.”
From Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials (2023) · cites this paper as [632]
Glutamine deprivation suppresses cancer growth and induces cell death in several cancers.
“Thus, glutamine deprivation suppresses cancer growth and even induces cell death in several cancers6,7.”
From Glutamine reliance in cell metabolism (2020) · cites this paper as [6]
In cancer cells, the use of glutamate-derived nitrogen for NEAA production may be favored to preserve nitrogen for anabolic reactions and may prevent apoptosis induced by ATF4 activation upon glutamine deprivation.
“In cancer cells, the use of glutamate-derived nitrogen for NEAA production may be favored in various types of cancer cells to preserve nitrogen for anabolic reactions48 and may prevent apoptosis induced by ATF4 activation upon glutamine deprivation6.”
From Glutamine reliance in cell metabolism (2020) · cites this paper as [6]
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
2 retracted
Ku70 suppresses the apoptotic translocation of Bax to mitochondria
Sawada, M., Sun, W., Hayes, P. L., Leskov, K., Boothman, D. A., & Matsuyama, S. (2003) · Nature Cell Biology · doi:10.1038/ncb950 · Cited by 353 · see citing works
Retracted(2007) · Nature Cell Biology · doi:10.1038/ncb1584 · Cited by 7 · see citing works
RetractedUnderstanding 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 · see citing works
Self-citationThe Biology of Cancer: Metabolic Reprogramming Fuels Cell Growth and Proliferation
DeBerardinis, R. J., Lum, J. J., Hatzivassiliou, G., & Thompson, C. B. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2007.10.002 · Cited by 4,088 · see citing works
Self-citationProapoptotic BAX and BAK: A Requisite Gateway to Mitochondrial Dysfunction and Death
Wei, M. C., Zong, W.-X., Cheng, E. H.-Y., Lindsten, T., Panoutsakopoulou, V., Ross, A. J., Roth, K. A., MacGregor, G. R., Thompson, C. B., & Korsmeyer, S. J. (2001) · Science · doi:10.1126/science.1059108 · Cited by 3,988 · see citing works
Self-citationDang, C. V. (2012) · Cell · doi:10.1016/j.cell.2012.03.003 · Cited by 3,390 · see citing works
Pàez‐Ribes, M., Allen, E., Hudock, J., Takeda, T., Okuyama, H., Viñals, F., Inoue, M., Bergers, G., Hanahan, D., & Casanovas, O. (2009) · Cancer Cell · doi:10.1016/j.ccr.2009.01.027 · Cited by 2,344 · 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
TIGAR, a p53-Inducible Regulator of Glycolysis and Apoptosis
Bensaad, K., Tsuruta, A., Selak, M. A., Vidal, M. N. C., Nakano, K., Bartrons, R., Gottlieb, E., & Vousden, K. H. (2006) · Cell · doi:10.1016/j.cell.2006.05.036 · Cited by 2,019 · 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
Self-citationRecent Advances in Neuroblastoma
Maris, J. M. (2010) · New England Journal of Medicine · doi:10.1056/nejmra0804577 · Cited by 1,991 · see citing works
Self-citationBidirectional Transport of Amino Acids Regulates mTOR and Autophagy
Nicklin, P., Bergman, P., Zhang, B., Triantafellow, E., Wang, H., Nyfeler, B., Yang, H., Hild, M., Kung, C., Wilson, C., et al. (2009) · Cell · doi:10.1016/j.cell.2008.11.044 · Cited by 1,798 · see citing works
Reductive glutamine metabolism by IDH1 mediates lipogenesis under hypoxia
Metallo, C. M., Gameiro, P. A., Bell, E. L., Mattaini, K. R., Yang, J., Hiller, K., Jewell, C. M., Johnson, Z. R., Irvine, D. J., Guarente, L., et al. (2012) · Nature · doi:10.1038/nature10602 · Cited by 1,791 · see citing works
Accelerated Metastasis after Short-Term Treatment with a Potent Inhibitor of Tumor Angiogenesis
Ebos, J. M. L., Lee, C. R., Cruz‐Muñoz, W., Bjarnason, G. A., Christensen, J. G., & Kerbel, R. S. (2009) · Cancer Cell · doi:10.1016/j.ccr.2009.01.021 · Cited by 1,710 · see citing works
Letai, A., Bassik, M. C., Walensky, L. D., Sorcinelli, M. D., Weiler, S., & Korsmeyer, S. J. (2002) · Cancer Cell · doi:10.1016/s1535-6108(02)00127-7 · Cited by 1,677 · see citing works
Identification of ALK as a major familial neuroblastoma predisposition gene
Mossé, Y. P., Laudenslager, M., Longo, L., Cole, K. A., Wood, A., Attiyeh, E. F., Laquaglia, M. J., Sennett, R., Lynch, J. E., Perri, P., et al. (2008) · Nature · doi:10.1038/nature07261 · Cited by 1,407 · see citing works
Self-citationReductive carboxylation supports growth in tumour cells with defective mitochondria
Mullen, A. R., Wheaton, W. W., Jin, E. S., Chen, P.-H., Sullivan, L. B., Cheng, T., Yang, Y., Linehan, W. M., Chandel, N. S., & DeBerardinis, R. J. (2012) · Nature · doi:10.1038/nature10642 · Cited by 1,328 · see citing works
Glucose-Independent Glutamine Metabolism via TCA Cycling for Proliferation and Survival in B Cells
Le, A., Lane, A. N., Hamaker, M., Bose, S., Gouw, A., Barbi, J., Tsukamoto, T., Rojas, C. J., Slusher, B. S., Zhang, H., et al. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2011.12.009 · Cited by 1,095 · see citing works
Ohoka, N., Yoshii, S., Hattori, T., Onozaki, K., & Hayashi, H. (2005) · The EMBO Journal · doi:10.1038/sj.emboj.7600596 · Cited by 1,004 · see citing works
Wise, D. R., Ward, P. S., Shay, J. E. S., Cross, J. R., Gruber, J. J., Sachdeva, U. M., Platt, J. M., DeMatteo, R. G., Simon, M. C., & Thompson, C. B. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1117773108 · Cited by 975 · see citing works
Self-citationMYC inactivation uncovers pluripotent differentiation and tumour dormancy in hepatocellular cancer
Shachaf, C. M., Kopelman, A. M., Arvanitis, C., Karlsson, Å., Beer, S., Mandl, S., Bachmann, M. H., Borowsky, A. D., Ruebner, B., Cardiff, R. D., et al. (2004) · Nature · doi:10.1038/nature03043 · Cited by 874 · see citing works
Modelling Myc inhibition as a cancer therapy
Soucek, L., Whitfield, J. R., Martins, C. P., Finch, A. J., Murphy, D. J., Sodir, N. M., Karnezis, A. N., Swigart, L. B., Nasi, S., & Evan, G. I. (2008) · Nature · doi:10.1038/nature07260 · Cited by 822 · 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
Teitz, T., Wei, T., Valentine, M. B., Vanin, E. F., Grenet, J. A., Valentine, V. A., Behm, F. G., Look, A. T., Lahti, J. M., & Kidd, V. J. (2000) · Nature Medicine · doi:10.1038/75007 · Cited by 809 · see citing works
Ye, J., Kumanova, M., Hart, L. S., Sloane, K. L., Zhang, H., Panis, D. N. D., Bobrovnikova-Marjon, E. V., Diehl, J. A., Ron, D., & Koumenis, C. (2010) · The EMBO Journal · doi:10.1038/emboj.2010.81 · Cited by 709 · see citing works
Deficiency in glutamine but not glucose induces MYC-dependent apoptosis in human cells
Yuneva, M., Zamboni, N., Oefner, P., Sachidanandam, R., & Lazebnik, Y. (2007) · The Journal of Cell Biology · doi:10.1083/jcb.200703099 · Cited by 690 · cited 3× · see citing works
“Consequently, Gln depletion kills transformed cells in a Myc-dependent manner (Le et al., 2012; Wise et al., 2008; Yuneva et al., 2007).”
ATF4-dependent transcription mediates signaling of amino acid limitation
Kilberg, M. S., Shan, J., & Su, N. Y. (2009) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2009.05.008 · Cited by 595 · see citing works
PUMA, a potent killer with or without p53
Yu, J., & Zhang, L. (2008) · Oncogene · doi:10.1038/onc.2009.45 · Cited by 560 · see citing works
Activating transcription factor 4
Ameri, K., & Harris, A. L. (2007) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2007.01.020 · Cited by 557 · see citing works
Butkinaree, C., Park, K., & Hart, G. W. (2009) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2009.07.018 · Cited by 415 · see citing works
Multitargeted therapy of cancer by green tea polyphenols
Khan, N., & Mukhtar, H. (2008) · Cancer Letters · doi:10.1016/j.canlet.2008.04.014 · Cited by 365 · see citing works
Galehdar, Z., Swan, P., Fuerth, B. J., Callaghan, S. M., Park, D. S., & Cregan, S. P. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.1598-10.2010 · Cited by 361 · see citing works
The stress-regulated protein p8 mediates cannabinoid-induced apoptosis of tumor cells
Carracedo, A., Lorente, M., Egia, A., Blázquez, C., Garcia, S., Giroux, V., Malicet, C., Villuendas, R., Gironella, M., González‐Feria, L., et al. (2006) · Cancer Cell · doi:10.1016/j.ccr.2006.03.005 · Cited by 354 · see citing works
Integrative genomics identifies LMO1 as a neuroblastoma oncogene
Wang, K. Y., Diskin, S. J., Zhang, H., et al. (2010) · Nature · doi:10.1038/nature09609 · Cited by 309 · see citing works
Common variations in BARD1 influence susceptibility to high-risk neuroblastoma
Capasso, M., Devoto, M., Hou, C., Asgharzadeh, S., Glessner, J., Attiyeh, E. F., Mossé, Y. P., Kim, C., Diskin, S. J., Cole, K. A., et al. (2009) · Nature Genetics · doi:10.1038/ng.374 · Cited by 304 · see citing works
Self-citationATF4 is an oxidative stress–inducible, prodeath transcription factor in neurons in vitro and in vivo
Lange, P. S., Chavez, J. C., Pinto, J. T., Coppola, G., Sun, C.-W., Townes, T. M., Geschwind, D. H., & Ratan, R. R. (2008) · The Journal of Experimental Medicine · doi:10.1084/jem.20071460 · Cited by 272 · cited 2× · see citing works
“In contrast to fibroblasts, ATF4 is a proapoptotic factor in neurons both in vitro and in vivo (Lange et al., 2008).”
Metabolism and action of amino acid analog anti-cancer agents
Ahluwalia, G. S., Grem, J. L., Hao, Z., & Cooney, D. A. (1990) · Pharmacology & Therapeutics · doi:10.1016/0163-7258(90)90094-i · Cited by 241 · see citing works
Eischen, C. M., Roussel, M. F., Korsmeyer, S. J., & Cleveland, J. L. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.22.7653-7662.2001 · Cited by 183 · see citing works
Qing, G., Skuli, N., Mayes, P. A., Pawel, B., Martinez, D., Maris, J. M., & Simon, M. C. (2010) · Cancer Research · doi:10.1158/0008-5472.can-10-0740 · Cited by 157 · see citing works
Self-citationVillablanca, J. G., Krailo, M., Ames, M. M., et al. (2006) · Journal of Clinical Oncology · doi:10.1200/jco.2005.03.9271 · Cited by 149 · see citing works
Corazzari, M., Lovat, P. E., Armstrong, J. L., Fimia, G. M., Hill, D. S., Birch-Machin, M., Redfern, C. P. F., & Piacentini, M. (2007) · British Journal of Cancer · doi:10.1038/sj.bjc.6603672 · Cited by 117 · see citing works
Porro, A., Haber, M., Diolaiti, D., Iraci, N., Henderson, M. J., Gherardi, S., Valli, E., Munoz, M. A., Xue, C., Flemming, C. L., et al. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.078584 · Cited by 110 · see citing works
Deregulated Wnt/β-catenin program in high-risk neuroblastomas without MYCN amplification
Liu, X., Mazánek, P., Dam, V., Wang, Q., Zhao, H., Guo, R. J., Jagannathan, J., Cnaan, A., Maris, J. M., & Hogarty, M. D. (2007) · Oncogene · doi:10.1038/sj.onc.1210769 · Cited by 109 · see citing works
Self-citationHigh Throughput Screening Reveals Several New Classes of Glutamate Dehydrogenase Inhibitors
Li, M., Allen, A., & Smith, T. J. (2007) · Biochemistry · doi:10.1021/bi7018783 · Cited by 44 · 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
ER-stress-induced transcriptional regulation increases protein synthesis leading to cell death
Han, J., Back, S. H., Hur, J., Lin, Y.-H., Gildersleeve, R., Shan, J., Yuan, C. L., Krokowski, D., Wang, S., Hatzoglou, M., et al. (2013) · Nature Cell Biology · doi:10.1038/ncb2738 · Cited by 1,691 · 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
Glutamine reliance in cell metabolism
Yoo, H. C., Yu, Y. C., Sung, Y., & Han, J. M. (2020) · Experimental & Molecular Medicine · doi:10.1038/s12276-020-00504-8 · Cited by 1,021 · see citing works
Yang, C., Ko, B., Hensley, C. T., Jiang, L., Wasti, A. T., Kim, J., Sudderth, J., Calvaruso, M. A., Lumata, L., Mitsche, M., et al. (2014) · Molecular Cell · doi:10.1016/j.molcel.2014.09.025 · Cited by 679 · see citing works
Cancer cell metabolism: the essential role of the nonessential amino acid, glutamine
Zhang, J., Pavlova, N. N., & Thompson, C. B. (2017) · The EMBO Journal · doi:10.15252/embj.201696151 · Cited by 651 · see citing works
Self-citationThe mTORC1 Pathway Stimulates Glutamine Metabolism and Cell Proliferation by Repressing SIRT4
Csibi, A., Fendt, S.-M., Li, C., Poulogiannis, G., Choo, A. Y., Chapski, D. J., Jeong, S. M., Dempsey, J. M., Parkhitko, A., Morrison, T., et al. (2013) · Cell · doi:10.1016/j.cell.2013.04.023 · Cited by 586 · see citing works
Glutaminolysis as a target for cancer therapy
Jin, L., Alesi, G. N., & Kang, S. (2016) · Oncogene · doi:10.1038/onc.2015.447 · Cited by 459 · see citing works
Asparagine Plays a Critical Role in Regulating Cellular Adaptation to Glutamine Depletion
Zhang, J., Fan, J., Venneti, S., Cross, J. R., Takagi, T., Bhinder, B., Djaballah, H., Kanai, M., Cheng, E. H., Judkins, A. R., et al. (2014) · Molecular Cell · doi:10.1016/j.molcel.2014.08.018 · Cited by 439 · see citing works
Self-citationRegulation of cancer cell metabolism: Oncogenic MYC in the driver’s seat
Dong, Y., Tu, R., Liu, H., & Qing, G. (2020) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-00235-2 · Cited by 405 · see citing works
Self-citationRecent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials
Xie, X., Yu, T., Li, X., Zhang, N., Foster, L. J., Peng, C., Huang, W., & He, G. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01589-z · Cited by 396 · see citing works
Dixon, S. J. (2017) · Immunological Reviews · doi:10.1111/imr.12533 · Cited by 314 · see citing works
Differential Glutamate Metabolism in Proliferating and Quiescent Mammary Epithelial Cells
Coloff, J. L., Murphy, J. P., Braun, C. R., Harris, I. S., Shelton, L. M., Kami, K., Gygi, S. P., Selfors, L. M., & Brugge, J. S. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.03.016 · Cited by 288 · see citing works
Oncogenic PIK3CA mutations reprogram glutamine metabolism in colorectal cancer
Hao, Y., Samuels, Y., Li, Q., Krokowski, D., Guan, B.-J., Wang, C., Jin, Z., Dong, B., Cao, B., Feng, X., et al. (2016) · Nature Communications · doi:10.1038/ncomms11971 · Cited by 290 · see citing works
MYC and tumor metabolism: chicken and egg
Dejure, F. R., & Eilers, M. (2017) · The EMBO Journal · doi:10.15252/embj.201796438 · Cited by 240 · see citing works
Gwinn, D. M., Lee, A. G., Briones-Martin-del-Campo, M., Conn, C. S., Simpson, D. R., Scott, A. I., Le, A., Cowan, T. M., Ruggero, D., & Sweet-Cordero, E. A. (2018) · Cancer Cell · doi:10.1016/j.ccell.2017.12.003 · Cited by 230 · see citing works
The Diverse Functions of Non-Essential Amino Acids in Cancer
Choi, B.-H., & Coloff, J. L. (2019) · Cancers · doi:10.3390/cancers11050675 · Cited by 213 · see citing works
Targeting Cancer Metabolism: Dietary and Pharmacologic Interventions
Vernieri, C., Casola, S., Foiani, M., Pietrantonio, F., de Braud, F., & Longo, V. (2016) · Cancer Discovery · doi:10.1158/2159-8290.cd-16-0615 · Cited by 202 · see citing works
Goetzman, E. S., & Prochownik, E. V. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00129 · Cited by 199 · see citing works
Targeting Glutamine Metabolism in Breast Cancer with Aminooxyacetate
Korangath, P., Teo, W. W., Sadik, H., Han, L., Mori, N., Huijts, C. M., Wildes, F., Bharti, S., Zhang, Z., Santa-Maria, C. A., et al. (2015) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-14-1200 · Cited by 182 · see citing works
Metabolic adaptation of cancer and immune cells mediated by hypoxia-inducible factors
Samanta, D., & Semenza, G. L. (2018) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2018.07.002 · Cited by 190 · see citing works
Targeting Glutamine Induces Apoptosis: A Cancer Therapy Approach
Chen, L., & Cui, H. (2015) · International Journal of Molecular Sciences · doi:10.3390/ijms160922830 · Cited by 184 · see citing works
Myc promotes glutaminolysis in human neuroblastoma through direct activation of glutaminase 2
Xiao, D., Ren, P., Su, H., Yue, M., Xiu, R., Hu, Y., Liu, H., & Qing, G. (2015) · Oncotarget · doi:10.18632/oncotarget.5821 · Cited by 80 · see citing works
Self-citationMyc-induced glutaminolysis bypasses HIF-driven glycolysis in hypoxic small cell lung carcinoma cells
Thorén, M. M., Vaapil, M., Staaf, J., Planck, M., Johansson, M. E., Mohlin, S., & Påhlman, S. (2017) · Oncotarget · doi:10.18632/oncotarget.16904 · Cited by 31 · see citing works
- Authors
- Qing, G., Li, B., Vu, A., Skuli, N., Walton, Z. E., Liu, X., Mayes, P. A., Wise, D. R., Thompson, C. B., Maris, J. M., Hogarty, M. D., & Simon, M. C.
- Affiliations
- Howard Hughes Medical Institute (US)
- Abramson Cancer Center (US)
- Children's Hospital of Philadelphia (US)
- Corresponding author
- Simon, M. Celeste
- ORCID
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2012-11
- Volume
- 22
- Issue
- 5
- Pages
- 631-644
- ISSN
- 1535-6108 (ISSN-L)
- PMC
- PMC3510660
- OpenAlex
- W2110508238
- Cited by
- 375
- References
- 44
- Citations by year
- 2026: 16 · 2025: 23 · 2024: 25 · 2023: 30 · 2022: 32 · 2021: 37 · 2020: 30 · 2019: 27 · 2018: 25 · 2017: 31 · 2016: 31 · 2015: 28 · 2014: 27 · 2013: 13
- FWCI
- 8.75
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 377 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cancer Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (1F32CA137988, CA104838, CA105463, CA97323)
- Howard Hughes Medical Institute
- National Natural Science Foundation of China (81171928)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Keywords
- ATF4, c-Myc, neuroblastoma, glutamine deprivation, apoptosis, PUMA, Noxa, TRB3, glutamine metabolism, aspartate aminotransferase, glutamate dehydrogenase, MYCN amplification
- MeSH terms
- Aminooxyacetic Acid, Animals, Glutamine, Humans, Mice, Inbred BALB C, Mice, Nude, Neuroblastoma, Proto-Oncogene Proteins, Repressor Proteins, Tumor Suppressor Protein p53, Proto-Oncogene Proteins c-myc, Apoptosis, Protein Serine-Threonine Kinases, Cell Cycle Proteins, Proto-Oncogene Proteins c-bcl-2, Caspases, Cell Proliferation, Apoptosis Regulatory Proteins, bcl-2-Associated X Protein, Mice, Activating Transcription Factor 4
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
