The DOI matches its Crossref record; 11 of the 11 references it cites were found in a registry or an index.
Metabolic reprogramming induces resistance to anti-NOTCH1 therapies in T cell acute lymphoblastic leukemia
Open accessAbstract
Activating mutations in NOTCH1 are common in T cell acute lymphoblastic leukemia (T-ALL). Here we identify glutaminolysis as a critical pathway for leukemia cell growth downstream of NOTCH1 and a key determinant of the response to anti-NOTCH1 therapies in vivo. Mechanistically, inhibition of NOTCH1 signaling in T-ALL induces a metabolic shutdown, with prominent inhibition of glutaminolysis and triggers autophagy as a salvage pathway supporting leukemia cell metabolism. Consequently, inhibition of glutaminolysis and inhibition of autophagy strongly and synergistically enhance the antileukemic effects of anti-NOTCH1 therapy in mice harboring T-ALL. Moreover, we demonstrate that Pten loss upregulates glycolysis and consequently rescues leukemic cell metabolism, thereby abrogating the antileukemic effects of NOTCH1 inhibition. Overall, these results identify glutaminolysis as a major node in cancer metabolism controlled by NOTCH1 and as therapeutic target for the treatment of T-ALL.
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Subramanian, A., Tamayo, P., Mootha, V. K., Mukherjee, S., Ebert, B. L., Gillette, M. A., Paulovich, A., Pomeroy, S. L., Golub, T. R., Lander, E. S., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506580102 · Cited by 53,625
Drug combination studies and their synergy quantification using the Chou-Talalay method
Chou, T.-C. (2010) · Cancer Research · doi:10.1158/0008-5472.can-09-1947 · Cited by 5,739
Impairment of starvation-induced and constitutive autophagy in Atg7 -deficient mice
Komatsu, M., Waguri, S., Ueno, T., Iwata, J., Murata, S., Tanida, I., Ezaki, J., Mizushima, N., Ohsumi, Y., Uchiyama, Y., et al. (2005) · The Journal of Cell Biology · doi:10.1083/jcb.200412022 · Cited by 2,331
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
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
Self-citationAkt Stimulates Aerobic Glycolysis in Cancer Cells
Elstrom, R. L., Bauer, D. E., Buzzai, M., Karnauskas, R., Harris, M. H., Plas, D. R., Zhuang, H., Cinalli, R. M., Alavi, A., Rudin, C. M., et al. (2004) · Cancer Research · doi:10.1158/0008-5472.can-03-2904 · Cited by 1,454
Phosphoglycerate dehydrogenase diverts glycolytic flux and contributes to oncogenesis
Locasale, J. W., Grassian, A. R., Melman, T., Lyssiotis, C. A., Mattaini, K. R., Bass, A. J., Heffron, G., Metallo, C. M., Muranen, T., Sharfi, H., et al. (2011) · Nature Genetics · doi:10.1038/ng.890 · Cited by 1,120
Heckl, D., Kowalczyk, M. S., Yudovich, D., Belizaire, R., Puram, R. V., McConkey, M. E., Thielke, A., Aster, J. C., Regev, A., & Ebert, B. L. (2014) · Nature Biotechnology · doi:10.1038/nbt.2951 · Cited by 555
ATP citrate lyase is an important component of cell growth and transformation
Bauer, D. E., Hatzivassiliou, G., Zhao, F., Andreadis, C., & Thompson, C. B. (2005) · Oncogene · doi:10.1038/sj.onc.1208773 · Cited by 537
Buzzai, M., Bauer, D. E., Jones, R. G., DeBerardinis, R. J., Hatzivassiliou, G., Elstrom, R. L., & Thompson, C. B. (2005) · Oncogene · doi:10.1038/sj.onc.1208622 · Cited by 357
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Fundamentals of Cancer Metabolism
DeBerardinis, R. J., & Chandel, N. S. (2016) · Science Advances · doi:10.1126/sciadv.1600200 · Cited by 3,013
Self-citationFrom 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
Notch signaling pathway: architecture, disease, and therapeutics
Zhou, B., Lin, W., Long, Y., Yang, Y., Zhang, H., Wu, K., & Chu, Q. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-00934-y · Cited by 1,114
Glutamine Metabolism in Cancer: Understanding the Heterogeneity
Cluntun, A. A., Lukey, M. J., Cerione, R. A., & Locasale, J. W. (2017) · Trends in Cancer · doi:10.1016/j.trecan.2017.01.005 · Cited by 796
Eelen, G., de Zeeuw, P., Treps, L., Harjes, U., Wong, B. W., & Carmeliet, P. (2018) · Physiological Reviews · doi:10.1152/physrev.00001.2017 · Cited by 572
Metadata
- Authors
- Herranz, D., Ambesi-Impiombato, A., Sudderth, J., Sánchez-Martín, M., Belver, L., Tosello, V., Xu, L., Wendorff, A. A., Castillo, M., Haydu, J. E., Márquez, J., Matés, J. M., Kung, A. L., Rayport, S., Cordon-Cardo, C., DeBerardinis, R. J., & Ferrando, A. A.
- Venue
- Nature Medicine
- Published
- 2015-09-21
- Volume
- 21
- Issue
- 10
- Pages
- 1182-1189
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W2196885702
- Cited by
- 208
- References
- 11
- FWCI
- 21.67
- Type
- journal article
- Language
- en
- Open access
- green
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- Herranz, D., Ambesi-Impiombato, A., Sudderth, J., Sánchez-Martín, M., Belver, L., Tosello, V., Xu, L., Wendorff, A. A., Castillo, M., Haydu, J. E., Márquez, J., Matés, J. M., Kung, A. L., Rayport, S., Cordon-Cardo, C., DeBerardinis, R. J., & Ferrando, A. A. (2015). Metabolic reprogramming induces resistance to anti-NOTCH1 therapies in T cell acute lymphoblastic leukemia. Nature Medicine. https://doi.org/10.1038/nm.3955
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
