The DOI matches its Crossref record; 52 of the 52 references it cites were found in a registry or an index.
SLC7A11 expression level dictates differential responses to oxidative stress in cancer cells
Open accessAbstract
The cystine transporter solute carrier family 7 member 11 (SLC7A11; also called xCT) protects cancer cells from oxidative stress and is overexpressed in many cancers. Here we report a surprising finding that, whereas moderate overexpression of SLC7A11 is beneficial for cancer cells treated with H 2 O 2, a common oxidative stress inducer, its high overexpression dramatically increases H 2 O 2-induced cell death. Mechanistically, high cystine uptake in cancer cells with high overexpression of SLC7A11 in combination with H 2 O 2 treatment results in toxic buildup of intracellular cystine and other disulfide molecules, NADPH depletion, redox system collapse, and rapid cell death (likely disulfidptosis). We further show that high overexpression of SLC7A11 promotes tumor growth but suppresses tumor metastasis, likely because metastasizing cancer cells with high expression of SLC7A11 are particularly susceptible to oxidative stress. Our findings reveal that SLC7A11 expression level dictates cancer cells’ sensitivity to oxidative stress and suggests a context-dependent role for SLC7A11 in tumor biology.
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Cites
Ferroptosis: An Iron-Dependent Form of Nonapoptotic Cell Death
Dixon, S. J., Lemberg, K. M., Lamprecht, M. R., Skouta, R., Zaitsev, E. M., Gleason, C. E., Patel, D. N., Bauer, A. J., Cantley, A. M., Yang, W. S., et al. (2012) · Cell · doi:10.1016/j.cell.2012.03.042 · Cited by 18,691
Ferroptosis as a p53-mediated activity during tumour suppression
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Cystine transporter SLC7A11/xCT in cancer: ferroptosis, nutrient dependency, and cancer therapy
Koppula, P., Zhuang, L., & Gan, B. (2021) · Protein & Cell · doi:10.1007/s13238-020-00789-5 · Cited by 2,487
Self-citationTargeting Ferroptosis as a Vulnerability in Cancer
Lei, G., Zhuang, L., & Gan, B. (2022) · Nature reviews. Cancer · doi:10.1038/s41568-022-00459-0 · Cited by 2,252
Self-citationDHODH-mediated ferroptosis defence is a targetable vulnerability in cancer
Mao, C., Liu, X., Zhang, Y., Lei, G., Yan, Y., Lee, H., Koppula, P., Wu, S., Zhuang, L., Fang, B., et al. (2021) · Nature · doi:10.1038/s41586-021-03539-7 · Cited by 1,900
Self-citationThe role of ROS in tumour development and progression
Cheung, E. C., & Vousden, K. H. (2022) · Nature Reviews Cancer · doi:10.1038/s41568-021-00435-0 · Cited by 1,595
The role of ferroptosis in ionizing radiation-induced cell death and tumor suppression
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Self-citationOxidative stress inhibits distant metastasis by human melanoma cells
Piskounova, E., Agathocleous, M., Murphy, M. M., Hu, Z., Huddlestun, S. E., Zhao, Z., Leitch, A. M., Johnson, T. M., DeBerardinis, R. J., & Morrison, S. J. (2015) · Nature · doi:10.1038/nature15726 · Cited by 1,269
Actin cytoskeleton vulnerability to disulfide stress mediates disulfidptosis
Liu, X., Nie, L., Zhang, Y., Yan, Y., Wang, C., Colic, M., Olszewski, K., Horbath, A., Chen, X., Lei, G., et al. (2023) · Nature Cell Biology · doi:10.1038/s41556-023-01091-2 · Cited by 1,132
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Cited by
Fan, Y., Xue, H., Li, Z., Huo, M., Gao, H., & Guan, X. (2024) · Frontiers in Pharmacology · doi:10.3389/fphar.2024.1345522 · Cited by 40
Shi, J., Cui, G., Jin, Y., Mi, B., Liu, K., Zhao, L., Bao, K., Lu, Z., Liu, J., Wang, Y., et al. (2024) · Advanced Healthcare Materials · doi:10.1002/adhm.202402474 · Cited by 18
Metadata
- Authors
- Yan, Y., Teng, H., Hang, Q., Kondiparthi, L., Lei, G., Horbath, A., Liu, X., Mao, C., Wu, S., Zhuang, L., James You, M., Poyurovsky, M. V., Ma, L., Olszewski, K., & Gan, B.
- Venue
- Nature Communications
- Published
- 2023-06-21
- Volume
- 14
- Issue
- 1
- Pages
- 3673-3673
- ISSN
- 2041-1723 (ISSN-L)
- OpenAlex
- W4381469200
- Cited by
- 341
- References
- 52
- FWCI
- 25.63
- Type
- journal article
- Language
- en
- Open access
- gold
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- Yan, Y., Teng, H., Hang, Q., Kondiparthi, L., Lei, G., Horbath, A., Liu, X., Mao, C., Wu, S., Zhuang, L., James You, M., Poyurovsky, M. V., Ma, L., Olszewski, K., & Gan, B. (2023). SLC7A11 expression level dictates differential responses to oxidative stress in cancer cells. Nature Communications. https://doi.org/10.1038/s41467-023-39401-9
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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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