The x(c)- cystine/glutamate antiporter: a potential target for therapy of cancer and other diseases - PubMed (original) (raw)
Review
. 2008 Jun;215(3):593-602.
doi: 10.1002/jcp.21366.
Affiliations
- PMID: 18181196
- DOI: 10.1002/jcp.21366
Review
The x(c)- cystine/glutamate antiporter: a potential target for therapy of cancer and other diseases
Maisie Lo et al. J Cell Physiol. 2008 Jun.
Abstract
The x(c) (-) cystine/glutamate antiporter is a major plasma membrane transporter for the cellular uptake of cystine in exchange for intracellular glutamate. Its main functions in the body are mediation of cellular cystine uptake for synthesis of glutathione essential for cellular protection from oxidative stress and maintenance of a cystine:cysteine redox balance in the extracellular compartment. In the past decade it has become evident that the x(c) (-) transporter plays an important role in various aspects of cancer, including: (i) growth and progression of cancers that have a critical growth requirement for extracellular cystine/cysteine, (ii) glutathione-based drug resistance, (iii) excitotoxicity due to excessive release of glutamate, and (iv) uptake of herpesvirus 8, a causative agent of Kaposi's sarcoma. The x(c) (-) transporter also plays a role in certain CNS and eye diseases. This review focuses on the expression and function of the x(c) (-) transporter in cells and tissues with particular emphasis on its role in disease pathogenesis. The potential use of x(c) (-) inhibitors (e.g., sulfasalazine) for arresting tumor growth and/or sensitizing cancers is discussed.
(c) 2008 Wiley-Liss, Inc.
Comment in
- The x(c)(-) cystine/glutamate antiporter (xCT) as a potential target for therapy of cancer: yet another cytotoxic anticancer approach?
Savaskan NE, Hahnen E, Eyüpoglu IY. Savaskan NE, et al. J Cell Physiol. 2009 Aug;220(2):531-2; author reply 533-4. doi: 10.1002/jcp.21795. J Cell Physiol. 2009. PMID: 19415694 No abstract available.
Similar articles
- Transport of L-[14C]cystine and L-[14C]cysteine by subtypes of high affinity glutamate transporters over-expressed in HEK cells.
Hayes D, Wiessner M, Rauen T, McBean GJ. Hayes D, et al. Neurochem Int. 2005 Jun;46(8):585-94. doi: 10.1016/j.neuint.2005.03.001. Epub 2005 Apr 12. Neurochem Int. 2005. PMID: 15863236 - The x(c)(-) cystine/glutamate antiporter (xCT) as a potential target for therapy of cancer: yet another cytotoxic anticancer approach?
Savaskan NE, Hahnen E, Eyüpoglu IY. Savaskan NE, et al. J Cell Physiol. 2009 Aug;220(2):531-2; author reply 533-4. doi: 10.1002/jcp.21795. J Cell Physiol. 2009. PMID: 19415694 No abstract available. - The xc- cystine/glutamate antiporter as a potential therapeutic target for small-cell lung cancer: use of sulfasalazine.
Guan J, Lo M, Dockery P, Mahon S, Karp CM, Buckley AR, Lam S, Gout PW, Wang YZ. Guan J, et al. Cancer Chemother Pharmacol. 2009 Aug;64(3):463-72. doi: 10.1007/s00280-008-0894-4. Epub 2008 Dec 24. Cancer Chemother Pharmacol. 2009. PMID: 19104813 - Identification, Expression, and Roles of the Cystine/Glutamate Antiporter in Ocular Tissues.
Martis RM, Knight LJ, Donaldson PJ, Lim JC. Martis RM, et al. Oxid Med Cell Longev. 2020 Jun 18;2020:4594606. doi: 10.1155/2020/4594606. eCollection 2020. Oxid Med Cell Longev. 2020. PMID: 32655769 Free PMC article. Review. - The oxidative stress-inducible cystine/glutamate antiporter, system x (c) (-) : cystine supplier and beyond.
Conrad M, Sato H. Conrad M, et al. Amino Acids. 2012 Jan;42(1):231-46. doi: 10.1007/s00726-011-0867-5. Epub 2011 Mar 16. Amino Acids. 2012. PMID: 21409388 Review.
Cited by
- SLC7A9 suppression increases chemosensitivity by inducing ferroptosis via the inhibition of cystine transport in gastric cancer.
Feng H, Yu J, Xu Z, Sang Q, Li F, Chen M, Chen Y, Yu B, Zhu N, Xia J, He C, Hou J, Wu X, Yan C, Zhu Z, Su L, Li J, Dai W, Li YY, Liu B. Feng H, et al. EBioMedicine. 2024 Oct 21;109:105375. doi: 10.1016/j.ebiom.2024.105375. Online ahead of print. EBioMedicine. 2024. PMID: 39437660 Free PMC article. - Identification of Disulfidptosis-Related Genes in Ischemic Stroke by Combining Single-Cell Sequencing, Machine Learning Algorithms, and In Vitro Experiments.
Zhao S, Zhuang H, Ji W, Cheng C, Liu Y. Zhao S, et al. Neuromolecular Med. 2024 Sep 15;26(1):39. doi: 10.1007/s12017-024-08804-2. Neuromolecular Med. 2024. PMID: 39278970 Free PMC article. - Disrupted glutamate homeostasis as a target for glioma therapy.
Biegański M, Szeliga M. Biegański M, et al. Pharmacol Rep. 2024 Sep 11. doi: 10.1007/s43440-024-00644-y. Online ahead of print. Pharmacol Rep. 2024. PMID: 39259492 Review. - Targeting cell death in NAFLD: mechanisms and targeted therapies.
Xu HL, Wan SR, An Y, Wu Q, Xing YH, Deng CH, Zhang PP, Long Y, Xu BT, Jiang ZZ. Xu HL, et al. Cell Death Discov. 2024 Sep 7;10(1):399. doi: 10.1038/s41420-024-02168-z. Cell Death Discov. 2024. PMID: 39244571 Free PMC article. Review. - Bridging the Gap in Cancer Research: Sulfur Metabolism of Leukemic Cells with a Focus on L-Cysteine Metabolism and Hydrogen Sulfide-Producing Enzymes.
Kaleta K, Janik K, Rydz L, Wróbel M, Jurkowska H. Kaleta K, et al. Biomolecules. 2024 Jun 24;14(7):746. doi: 10.3390/biom14070746. Biomolecules. 2024. PMID: 39062461 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Miscellaneous