The DOI matches its Crossref record; 45 of the 45 references it cites were found in a registry or an index.
Iron addiction: a novel therapeutic target in ovarian cancer
Open accessAbstract
Ovarian cancer is a lethal malignancy that has not seen a major therapeutic advance in over 30 years. We demonstrate that ovarian cancer exhibits a targetable alteration in iron metabolism. Ferroportin (FPN), the iron efflux pump, is decreased, and transferrin receptor (TFR1), the iron importer, is increased in tumor tissue from patients with high grade but not low grade serous ovarian cancer. A similar profile of decreased FPN and increased TFR1 is observed in a genetic model of ovarian cancer tumor-initiating cells (TICs). The net result of these changes is an accumulation of excess intracellular iron and an augmented dependence on iron for proliferation. A forced reduction in intracellular iron reduces the proliferation of ovarian cancer TICs in vitro, and inhibits both tumor growth and intraperitoneal dissemination of tumor cells in vivo. Mechanistic studies demonstrate that iron increases metastatic spread by facilitating invasion through expression of matrix metalloproteases and synthesis of interleukin 6 (IL-6). We show that the iron dependence of ovarian cancer TICs renders them exquisitely sensitive in vivo to agents that induce iron-dependent cell death (ferroptosis) as well as iron chelators, and thus creates a metabolic vulnerability that can be exploited therapeutically.
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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
Regulation of Ferroptotic Cancer Cell Death by GPX4
Yang, W. S., SriRamaratnam, R., Welsch, M. E., Shimada, K., Skouta, R., Viswanathan, V. S., Cheah, J. H., Clemons, P. A., Shamji, A. F., Clish, C. B., et al. (2014) · Cell · doi:10.1016/j.cell.2013.12.010 · Cited by 7,713
Ferroptosis: Death by Lipid Peroxidation
Yang, W. S., & Stockwell, B. R. (2016) · Trends in Cell Biology · doi:10.1016/j.tcb.2015.10.014 · Cited by 3,088
The role of iron and reactive oxygen species in cell death
Dixon, S. J., & Stockwell, B. R. (2014) · Nature Chemical Biology · doi:10.1038/nchembio.1416 · Cited by 2,381
Ovarian Cancer Development and Metastasis
Lengyel, E. (2010) · The American Journal of Pathology · doi:10.2353/ajpath.2010.100105 · Cited by 1,672
Iron and cancer: more ore to be mined
Torti, S. V., & Torti, F. M. (2013) · Nature Reviews Cancer · doi:10.1038/nrc3495 · Cited by 1,621
Self-citationNovel Molecular Subtypes of Serous and Endometrioid Ovarian Cancer Linked to Clinical Outcome
Tothill, R. W., Tinker, A. V., George, J., Brown, R., Fox, S. B., Lade, S., Johnson, D. S., Trivett, M. K., Etemadmoghadam, D., Locandro, B., et al. (2008) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-08-0196 · Cited by 1,467
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Evaluating cell lines as tumour models by comparison of genomic profiles
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The biology of ovarian cancer: new opportunities for translation
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Cited by
Ferroptosis: past, present and future
Li, J., Cao, F., Yin, H.-L., Huang, Z.-J., Lin, Z.-T., Mao, N., Sun, B., & Wang, G. (2020) · Cell Death & Disease · doi:10.1038/s41419-020-2298-2 · Cited by 4,171
Role of GPX4 in ferroptosis and its pharmacological implication
Seibt, T. M., Proneth, B., & Conrad, M. (2019) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2018.09.014 · Cited by 1,520
Ferroptosis in cancer and cancer immunotherapy
Zhao, L., Zhou, X., Xie, F., Zhang, L., Yan, H., Huang, J., Zhang, C., Zhou, F., Chen, J., & Zhang, L. (2022) · Cancer Communications · doi:10.1002/cac2.12250 · Cited by 684
Mitochondria regulation in ferroptosis
Wang, H., Liu, C., Zhao, Y., & Gao, G. (2020) · European Journal of Cell Biology · doi:10.1016/j.ejcb.2019.151058 · Cited by 650
Molecular mechanisms of ferroptosis and its role in cancer therapy
Xu, T., Ding, W., Ji, X., Ao, X., Liu, Y., Yu, W., & Wang, J. (2019) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.14511 · Cited by 639
Metadata
- Authors
- Basuli, D., Tesfay, L., Deng, Z., Paul, B., Yamamoto, Y., Ning, G., Xian, W., McKeon, F., Lynch, M., Crum, C. P., Hegde, P., Brewer, M., Wang, X., Miller, L. D., Dyment, N., Torti, F. M., & Torti, S. V.
- Venue
- Oncogene
- Published
- 2017-03-20
- Volume
- 36
- Issue
- 29
- Pages
- 4089-4099
- ISSN
- 0950-9232 (ISSN-L)
- 1476-5594
- OpenAlex
- W2604049161
- Cited by
- 465
- References
- 45
- FWCI
- 18.22
- Type
- journal article
- Language
- en
- Open access
- green
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- Basuli, D., Tesfay, L., Deng, Z., Paul, B., Yamamoto, Y., Ning, G., Xian, W., McKeon, F., Lynch, M., Crum, C. P., Hegde, P., Brewer, M., Wang, X., Miller, L. D., Dyment, N., Torti, F. M., & Torti, S. V. (2017). Iron addiction: a novel therapeutic target in ovarian cancer. Oncogene. https://doi.org/10.1038/onc.2017.11
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