The DOI matches its Crossref record; 19 of the 19 references it cites were found in a registry or an index.
Yap reprograms glutamine metabolism to increase nucleotide biosynthesis and enable liver growth
Open accessAbstract
The Hippo pathway is an important regulator of organ size and tumorigenesis. It is unclear, however, how Hippo signalling provides the cellular building blocks required for rapid growth. Here, we demonstrate that transgenic zebrafish expressing an activated form of the Hippo pathway effector Yap1 (also known as YAP) develop enlarged livers and are prone to liver tumour formation. Transcriptomic and metabolomic profiling identify that Yap1 reprograms glutamine metabolism. Yap1 directly enhances glutamine synthetase (glul) expression and activity, elevating steady-state levels of glutamine and enhancing the relative isotopic enrichment of nitrogen during de novo purine and pyrimidine biosynthesis. Genetic or pharmacological inhibition of GLUL diminishes the isotopic enrichment of nitrogen into nucleotides, suppressing hepatomegaly and the growth of liver cancer cells. Consequently, Yap-driven liver growth is susceptible to nucleotide inhibition. Together, our findings demonstrate that Yap1 integrates the anabolic demands of tissue growth during development and tumorigenesis by reprogramming nitrogen metabolism to stimulate nucleotide biosynthesis.
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Fiji: an open-source platform for biological-image analysis
Schindelin, J., Arganda-Carreras, I., Frise, E., Kaynig, V., Longair, M., Pietzsch, T., Preibisch, S., Rueden, C., Saalfeld, S., Schmid, B., et al. (2012) · Nature Methods · doi:10.1038/nmeth.2019 · Cited by 66,890
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
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-citationRegulation of the Hippo-YAP Pathway by G-Protein-Coupled Receptor Signaling
Yu, F.-X., Zhao, B., Panupinthu, N., Jewell, J. L., Lian, I., Wang, L. H., Zhao, J., Yuan, H., Tumaneng, K., Li, H., et al. (2012) · Cell · doi:10.1016/j.cell.2012.06.037 · Cited by 1,628
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
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Camargo, F. D., Gokhale, S., Johnnidis, J. B., Fu, D., Bell, G. W., Jaenisch, R., & Brummelkamp, T. R. (2007) · Current Biology · doi:10.1016/j.cub.2007.10.039 · Cited by 1,252
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Yimlamai, D., Christodoulou, C., Galli, G. G., Yanger, K., Pepe-Mooney, B., Gurung, B., Shrestha, K., Cahan, P., Stanger, B. Z., & Camargo, F. D. (2014) · Cell · doi:10.1016/j.cell.2014.03.060 · Cited by 857
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Ben-Sahra, I., Hoxhaj, G., Ricoult, S. J. H., Asara, J. M., & Manning, B. D. (2016) · Science · doi:10.1126/science.aad0489 · Cited by 795
Self-citationβ-Catenin-Driven Cancers Require a YAP1 Transcriptional Complex for Survival and Tumorigenesis
Rosenbluh, J., Nijhawan, D., Cox, A. G., Li, X., Neal, J. T., Schafer, E. J., Zack, T. I., Wang, X., Tsherniak, A., Schinzel, A. C., et al. (2012) · Cell · doi:10.1016/j.cell.2012.11.026 · Cited by 757
Self-citationThe metabolic profile of tumors depends on both the responsible genetic lesion and tissue type
Yuneva, M. O., Fan, T. W. M., Allen, T. D., Higashi, R. M., Ferraris, D. V., Tsukamoto, T., Matés, J. M., Alonso, F. J., Wang, C., Seo, Y., et al. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2011.12.015 · Cited by 639
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Zhang, J., Pavlova, N. N., & Thompson, C. B. (2017) · The EMBO Journal · doi:10.15252/embj.201696151 · Cited by 651
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Metadata
- Authors
- Cox, A. G., Hwang, K. L., Brown, K. K., Evason, K. J., Beltz, S., Tsomides, A., O’Connor, K., Galli, G. G., Yimlamai, D., Chhangawala, S., Yuan, M., Lien, E. C., Wucherpfennig, J., Nissim, S., Minami, A., Cohen, D. E., Camargo, F. D., Asara, J. M., Houvras, Y., Stainier, D. Y. R., & Goessling, W.
- Venue
- Nature Cell Biology
- Published
- 2016-07-18
- Volume
- 18
- Issue
- 8
- Pages
- 886-896
- ISSN
- 1465-7392 (ISSN-L)
- 1476-4679
- OpenAlex
- W2502710489
- Cited by
- 215
- References
- 19
- FWCI
- 13.30
- Type
- journal article
- Language
- en
- Open access
- green
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- Cox, A. G., Hwang, K. L., Brown, K. K., Evason, K. J., Beltz, S., Tsomides, A., O’Connor, K., Galli, G. G., Yimlamai, D., Chhangawala, S., Yuan, M., Lien, E. C., Wucherpfennig, J., Nissim, S., Minami, A., Cohen, D. E., Camargo, F. D., Asara, J. M., Houvras, Y., . . . Goessling, W. (2016). Yap reprograms glutamine metabolism to increase nucleotide biosynthesis and enable liver growth. Nature Cell Biology. https://doi.org/10.1038/ncb3389
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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.
