The DOI matches its Crossref record; 13 of the 13 references it cites were found in a registry or an index.
Metallothionein‐1G facilitates sorafenib resistance through inhibition of ferroptosis
Open accessAbstract
Hepatocellular carcinoma (HCC) is a major cause of cancer‐related death worldwide and currently has the fastest rising incidence of all cancers. Sorafenib was originally identified as an inhibitor of multiple oncogenic kinases and remains the only approved systemic therapy for advanced HCC. However, acquired resistance to sorafenib has been found in HCC patients, which results in poor prognosis. Here, we show that metallothionein (MT)‐1G is a critical regulator and promising therapeutic target of sorafenib resistance in human HCC cells. The expression of MT‐1G messenger RNA and protein is remarkably induced by sorafenib but not other clinically relevant kinase inhibitors (e.g., erlotinib, gefitinib, tivantinib, vemurafenib, selumetinib, imatinib, masitinib, and ponatinib). Activation of the transcription factor nuclear factor erythroid 2‐related factor 2, but not p53 and hypoxia‐inducible factor 1‐alpha, is essential for induction of MT‐1G expression following sorafenib treatment. Importantly, genetic and pharmacological inhibition of MT‐1G enhances the anticancer activity of sorafenib in vitro and in tumor xenograft models. The molecular mechanisms underlying the action of MT‐1G in sorafenib resistance involve the inhibition of ferroptosis, a novel form of regulated cell death. Knockdown of MT‐1G by RNA interference increases glutathione depletion and lipid peroxidation, which contributes to sorafenib‐induced ferroptosis. Conclusion: These findings demonstrate a novel molecular mechanism of sorafenib resistance and suggest that MT‐1G is a new regulator of ferroptosis in HCC cells. (H epatology 2016;64:488‐500)
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Regulation of Ferroptotic Cancer Cell Death by GPX4
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Role of nrf2 in oxidative stress and toxicity
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Inactivation of the ferroptosis regulator Gpx4 triggers acute renal failure in mice
Friedmann Angeli, J. P., Schneider, M., Proneth, B., Tyurina, Y. Y., Tyurin, V. A., Hammond, V. J., Herbach, N., Aichler, M., Walch, A., Eggenhofer, E., et al. (2014) · Nature Cell Biology · doi:10.1038/ncb3064 · Cited by 3,732
Ferroptosis: process and function
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Self-citationFerroptosis as a p53-mediated activity during tumour suppression
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Cited by
Ferroptosis: A Regulated Cell Death Nexus Linking Metabolism, Redox Biology, and Disease
Stockwell, B. R., Friedmann Angeli, J. P., Bayir, H., Bush, A. I., Conrad, M., Dixon, S. J., Fulda, S., Gascón, S., Hatzios, S. K., Kagan, V. E., et al. (2017) · Cell · doi:10.1016/j.cell.2017.09.021 · Cited by 7,695
Self-citationGalluzzi, L., Vitale, I., Aaronson, S. A., Abrams, J. M., Adam, D., Agostinis, P., Alnemri, E. S., Altucci, L., Amelio, I., Andrews, D. W., et al. (2018) · Cell Death & Differentiation · doi:10.1038/s41418-017-0012-4 · Cited by 6,680
Self-citationFerroptosis: 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
Autophagy promotes ferroptosis by degradation of ferritin
Hou, W., Xie, Y., Song, X., Sun, X., Lotze, M. T., Zeh, H. J., Kang, R., & Tang, D. (2016) · Autophagy · doi:10.1080/15548627.2016.1187366 · Cited by 2,332
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
Metadata
- Authors
- Sun, X., Niu, X., Chen, R., He, W., Chen, D., Kang, R., & Tang, D.
- Venue
- Hepatology
- Published
- 2016-05-24
- Volume
- 64
- Issue
- 2
- Pages
- 488-500
- ISSN
- 0270-9139 (ISSN-L)
- 1527-3350
- OpenAlex
- W2305753128
- Cited by
- 703
- References
- 13
- FWCI
- 22.51
- Type
- journal article
- Language
- en
- Open access
- bronze
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