The DOI matches its Crossref record; 31 of the 31 references it cites were found in a registry or an index.
NRF2 regulates serine biosynthesis in non–small cell lung cancer
Open accessAbstract
Tumors have high energetic and anabolic needs for rapid cell growth and proliferation, and the serine biosynthetic pathway was recently identified as an important source of metabolic intermediates for these processes. We integrated metabolic tracing and transcriptional profiling of a large panel of non–small cell lung cancer (NSCLC) cell lines to characterize the activity and regulation of the serine/glycine biosynthetic pathway in NSCLC. Here we show that the activity of this pathway is highly heterogeneous and is regulated by NRF2, a transcription factor frequently deregulated in NSCLC. We found that NRF2 controls the expression of the key serine/glycine biosynthesis enzyme genes PHGDH, PSAT1 and SHMT2 via ATF4 to support glutathione and nucleotide production. Moreover, we show that expression of these genes confers poor prognosis in human NSCLC. Thus, a substantial fraction of human NSCLCs activates an NRF2-dependent transcriptional program that regulates serine and glycine metabolism and is linked to clinical aggressiveness.
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Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation
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The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity
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Regulated Translation Initiation Controls Stress-Induced Gene Expression in Mammalian Cells
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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
Self-citationFunctional genomics reveal that the serine synthesis pathway is essential in breast cancer
Possemato, R., Marks, K. M., Shaul, Y. D., Pacold, M. E., Kim, D., Birsoy, K., Sethumadhavan, S., Woo, H.-K., Jang, H. G., Jha, A. K., et al. (2011) · Nature · doi:10.1038/nature10350 · Cited by 1,683
Nrf2 Redirects Glucose and Glutamine into Anabolic Pathways in Metabolic Reprogramming
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Reductive carboxylation supports growth in tumour cells with defective mitochondria
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Cited by
Fundamentals of Cancer Metabolism
DeBerardinis, R. J., & Chandel, N. S. (2016) · Science Advances · doi:10.1126/sciadv.1600200 · Cited by 3,013
Self-citationHayes, J. D., Dinkova-Kostova, A. T., & Tew, K. D. (2020) · Cancer Cell · doi:10.1016/j.ccell.2020.06.001 · Cited by 2,654
One-Carbon Metabolism in Health and Disease
Ducker, G. S., & Rabinowitz, J. D. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2016.08.009 · Cited by 2,239
The KEAP1-NRF2 system: a thiol-based sensor-effector apparatus for maintaining redox homeostasis
Yamamoto, M., Kensler, T. W., & Motohashi, H. (2018) · Physiological Reviews · doi:10.1152/physrev.00023.2017 · Cited by 1,968
NRF2, a Transcription Factor for Stress Response and Beyond
He, F., Ru, X., & Wen, T. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21134777 · Cited by 1,820
Metadata
- Authors
- DeNicola, G. M., Chen, P.-H., Mullarky, E., Sudderth, J. A., Hu, Z., Wu, D., Tang, H., Xie, Y., Asara, J. M., Huffman, K. E., Wistuba, I. I., Minna, J. D., DeBerardinis, R. J., & Cantley, L. C.
- Venue
- Nature Genetics
- Published
- 2015-10-19
- Volume
- 47
- Issue
- 12
- Pages
- 1475-1481
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W2173466127
- Cited by
- 746
- References
- 31
- FWCI
- 15.60
- Type
- journal article
- Language
- en
- Open access
- green
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- DeNicola, G. M., Chen, P.-H., Mullarky, E., Sudderth, J. A., Hu, Z., Wu, D., Tang, H., Xie, Y., Asara, J. M., Huffman, K. E., Wistuba, I. I., Minna, J. D., DeBerardinis, R. J., & Cantley, L. C. (2015). NRF2 regulates serine biosynthesis in non–small cell lung cancer. Nature Genetics. https://doi.org/10.1038/ng.3421
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