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Cited by 322

The DOI matches its Crossref record; 86 of the 86 references it cites were found in a registry or an index.

A targetable LIFR−NF-κB−LCN2 axis controls liver tumorigenesis and vulnerability to ferroptosis

Open access
Yao, Fan, Deng, Yalan, Zhao, Yang, Mei, Ying, Zhang, Yilei, Liu, Xiaoguang, Martinez, Consuelo, Su, Xiaohua, Rosato, Roberto R., Teng, Hongqi, Hang, Qinglei, Yap, Shannon, Chen, Dahu, Wang, Yumeng, Chen, Mei-Ju May, Zhang, Mutian, Liang, Han, Xie, Dong, Chen, Xin, Zhu, Hao, Chang, Jenny C., You, M. James, Sun, Yutong, Gan, Boyi, Ma, Li·2021·Nature Communications
DOI 10.1038/s41467-021-27452-9
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Abstract

The growing knowledge of ferroptosis has suggested the role and therapeutic potential of ferroptosis in cancer, but has not been translated into effective therapy. Liver cancer, primarily hepatocellular carcinoma (HCC), is highly lethal with limited treatment options. LIFR is frequently downregulated in HCC. Here, by studying hepatocyte-specific and inducible Lifr-knockout mice, we show that loss of Lifr promotes liver tumorigenesis and confers resistance to drug-induced ferroptosis. Mechanistically, loss of LIFR activates NF-κB signaling through SHP1, leading to upregulation of the iron-sequestering cytokine LCN2, which depletes iron and renders insensitivity to ferroptosis inducers. Notably, an LCN2-neutralizing antibody enhances the ferroptosis-inducing and anticancer effects of sorafenib on HCC patient-derived xenograft tumors with low LIFR expression and high LCN2 expression. Thus, anti-LCN2 therapy is a promising way to improve liver cancer treatment by targeting ferroptosis.

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Metadata

Authors
Yao, F., Deng, Y., Zhao, Y., Mei, Y., Zhang, Y., Liu, X., Martinez, C., Su, X., Rosato, R. R., Teng, H., Hang, Q., Yap, S., Chen, D., Wang, Y., Chen, M.-J. M., Zhang, M., Liang, H., Xie, D., Chen, X., Zhu, H., Chang, J. C., You, M. J., Sun, Y., Gan, B., & Ma, L.
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2021-12-17
Volume
12
Issue
1
Pages
7333-7333
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-021-27452-9
OpenAlex
W4200614050
Cited by
322
References
86
FWCI
28.79
Type
journal article
Language
en
Open access
gold

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CoChat. (2026). Citation check: A targetable LIFR−NF-κB−LCN2 axis controls liver tumorigenesis and vulnerability to ferroptosis. https://app.cochat.ai/papers/10.1038/s41467-021-27452-9
The paper
Yao, F., Deng, Y., Zhao, Y., Mei, Y., Zhang, Y., Liu, X., Martinez, C., Su, X., Rosato, R. R., Teng, H., Hang, Q., Yap, S., Chen, D., Wang, Y., Chen, M.-J. M., Zhang, M., Liang, H., Xie, D., Chen, X., . . . Ma, L. (2021). A targetable LIFR−NF-κB−LCN2 axis controls liver tumorigenesis and vulnerability to ferroptosis. Nature Communications. https://doi.org/10.1038/s41467-021-27452-9

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.