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Cited by 703

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 access
Sun, Xiaofang, Niu, Xiaohua, Chen, Ruochan, He, Wenyin, Chen, De, Kang, Rui, Tang, Daolin·2016·Hepatology

Abstract

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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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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CoChat. (2026). Citation check: Metallothionein‐1G facilitates sorafenib resistance through inhibition of ferroptosis. https://app.cochat.ai/papers/10.1002/hep.28574
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Sun, X., Niu, X., Chen, R., He, W., Chen, D., Kang, R., & Tang, D. (2016). Metallothionein‐1G facilitates sorafenib resistance through inhibition of ferroptosis. Hepatology. https://doi.org/10.1002/hep.28574

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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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