The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.
Stromal control of cystine metabolism promotes cancer cell survival in chronic lymphocytic leukaemia
Open accessAbstract
Tissue stromal cells interact with leukaemia cells and profoundly affect their viability and drug sensitivity. Here we show a biochemical mechanism by which bone marrow stromal cells modulate the redox status of chronic lymphocytic leukaemia (CLL) cells and promote cellular survival and drug resistance. Primary CLL cells from patients exhibit a limited ability to transport cystine for glutathione (GSH) synthesis owing to a low expression level of Xc-transporter. In contrast, bone marrow stromal cells effectively import cystine and convert it to cysteine, which is then released into the microenvironment for uptake by CLL cells to promote GSH synthesis. The elevated level of GSH enhances leukaemia cell survival and protects them from drug-induced cytotoxicity. Furthermore, disabling this protective mechanism significantly sensitizes CLL cells to drug treatment in the stromal environment. This stromal–leukaemia interaction is critical for CLL cell survival and represents a key biochemical pathway for effectively targeting leukaemia cells to overcome drug resistance in vivo.
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Cites
Cancer-associated IDH1 mutations produce 2-hydroxyglutarate
Dang, L., White, D. W., Gross, S., Bennett, B. D., Bittinger, M. A., Driggers, E. M., Fantin, V. R., Jang, H. G., Jin, S., Keenan, M. C., et al. (2009) · Nature · doi:10.1038/nature08617 · Cited by 4,154
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Gout, P., Buckley, A., Simms, C., & Bruchovsky, N. (2001) · Leukemia · doi:10.1038/sj.leu.2402238 · Cited by 640
Cancer-associated IDH1 mutations produce 2-hydroxyglutarate
Dang, L., White, D. W., Gross, S., Bennett, B. D., Bittinger, M. A., Driggers, E. M., Fantin, V. R., Jang, H. G., Jin, S., Keenan, M. C., et al. (2010) · Nature · doi:10.1038/nature09132 · Cited by 613
Analysis of the Adult Human Plasma Metabolome
Lawton, K. A., Berger, A., Mitchell, M., Milgram, K. E., Evans, A. M., Guo, L., Hanson, R. W., Kalhan, S. C., Ryals, J. A., & Milburn, M. V. (2008) · Pharmacogenomics · doi:10.2217/14622416.9.4.383 · Cited by 490
Redox imbalance in cystine/glutamate transporter-deficient mice
Sato, H., Shiiya, A., Kimata, M., Maebara, K., Tamba, M., Sakakura, Y., Makino, N., Sugiyama, F., Yagami, K.-I., Moriguchi, T., et al. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m506439200 · Cited by 422
The x cystine/glutamate antiporter: A potential target for therapy of cancer and other diseases
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Cited by
Modulation of oxidative stress as an anticancer strategy
Gorrini, C., Harris, I. S., & Mak, T. W. (2013) · Nature Reviews Drug Discovery · doi:10.1038/nrd4002 · Cited by 3,579
Koppula, P., Zhang, Y., Zhuang, L., & Gan, B. (2018) · Cancer Communications · doi:10.1186/s40880-018-0288-x · Cited by 915
Metabolic Interactions in the Tumor Microenvironment
Lyssiotis, C. A., & Kimmelman, A. C. (2017) · Trends in Cell Biology · doi:10.1016/j.tcb.2017.06.003 · Cited by 853
“However, chronic lymphoid leukemia (CLL) cells were found to be unable to readily take up cystine because they express very low levels of the transporter, system X (xCT) [75].”
BackgroundMetabolism of immune cells in cancer
Leone, R. D., & Powell, J. D. (2020) · Nature Reviews Cancer · doi:10.1038/s41568-020-0273-y · Cited by 877
Mechanisms and Implications of Metabolic Heterogeneity in Cancer
Kim, J., & DeBerardinis, R. J. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.08.013 · Cited by 606
Metadata
- Authors
- Zhang, W., Trachootham, D., Liu, J., Chen, G., Pelicano, H., Garcia-Prieto, C., Lu, W., Burger, J. A., Croce, C. M., Plunkett, W., Keating, M. J., & Huang, P.
- Venue
- Nature Cell Biology
- Published
- 2012-02-19
- Volume
- 14
- Issue
- 3
- Pages
- 276-286
- ISSN
- 1465-7392 (ISSN-L)
- 1476-4679
- OpenAlex
- W2058376258
- Cited by
- 357
- References
- 7
- FWCI
- 13.19
- Type
- journal article
- Language
- en
- Open access
- green
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- Zhang, W., Trachootham, D., Liu, J., Chen, G., Pelicano, H., Garcia-Prieto, C., Lu, W., Burger, J. A., Croce, C. M., Plunkett, W., Keating, M. J., & Huang, P. (2012). Stromal control of cystine metabolism promotes cancer cell survival in chronic lymphocytic leukaemia. Nature Cell Biology. https://doi.org/10.1038/ncb2432
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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