Evidence map›Paper›PMID 34921145›Full record

ArticleNature communications2021

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

Fan Yao, Yalan Deng, Yang Zhao, Ying Mei, Yilei Zhang, Xiaoguang Liu, Consuelo Martinez, Xiaohua Su, Roberto R Rosato, Hongqi Teng and 15 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 200 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
200citing papers in PubMed, 1 pooled it
34.9field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

200 citing papers in PubMed, 1 synthesis or guideline pooled it, 329 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Ferroptosis in liver biology and diseases.Hepatology communications · 2026
    Review
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140 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

25 authors at 6 institutions in 2 countries.

Fan Yao *Hubei Hongshan Laboratory, College of Life Science and Technology, College of Biomedicine and Health, Huazhong Agricultural University, Wuhan, Hubei, 430070, China. fyao@mail.hzau.edu.cn.ORCID http://orcid.org/0000-0002-4393-7296
Yalan Deng *Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.ORCID http://orcid.org/0000-0002-3954-3243
Yang ZhaoDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Ying MeiDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Yilei ZhangDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Xiaoguang LiuDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.ORCID http://orcid.org/0000-0001-6977-5128
Consuelo MartinezDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Xiaohua SuDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Roberto R RosatoHouston Methodist Cancer Center, Houston Methodist Hospital, Houston, TX, 77030, USA.ORCID http://orcid.org/0000-0002-7885-5127
Hongqi TengDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Qinglei HangDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.ORCID http://orcid.org/0000-0003-0419-6621
Shannon YapDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Dahu ChenDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Yumeng WangDepartment of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Mei-Ju May ChenDepartment of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.ORCID http://orcid.org/0000-0002-8721-0304
Mutian ZhangInstitute of Biosciences and Technology, Texas A&M University, Houston, TX, 77030, USA.
Han LiangDepartment of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.ORCID http://orcid.org/0000-0001-7633-286X
Dong XieCAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.ORCID http://orcid.org/0000-0002-1150-8657
Xin ChenDepartment of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA, 94143, USA.ORCID http://orcid.org/0000-0002-9588-0164
Hao ZhuChildren's Research Institute, Departments of Pediatrics and Internal Medicine, Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.ORCID http://orcid.org/0000-0002-8417-9698
Jenny C ChangHouston Methodist Cancer Center, Houston Methodist Hospital, Houston, TX, 77030, USA.
M James YouDepartment of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Yutong SunDepartment of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Boyi GanDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.ORCID http://orcid.org/0000-0001-8884-6040
Li MaDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA. lma4@mdanderson.org.ORCID http://orcid.org/0000-0001-9965-989X
The University of Texas MD Anderson Cancer Center · USMethodist Hospital · USShanghai Institute of Nutrition and Health · CNTexas A&M University · USThe University of Texas Southwestern Medical Center · USUniversity of California, San Francisco · US

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Scott Kopetz · 1985 to 2026
$290.8M
Regulation of metastasis and epithelial-mesenchymal transition by microRNAsR01CA166051 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI MA, LI · 2012 to 2023
$3.4M
Studying metabolic stress signaling in renal cancerR01CA181196 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI GAN, BOYI · 2014 to 2024
$3.4M
Targeting ferroptosis in radioresistance in lung cancer: mechanisms and preclinical translationR01CA247992 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI GAN, BOYI · 2021 to 2025
$1.9M
NCI NIH HHS P30 CA016672NCI NIH HHS R01 CA166051NCI NIH HHS R01 CA181196NCI NIH HHS R01 CA247992
6 · The paper itself

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.

Indexed as

FerroptosisAnimalsAntibodies, NeutralizingCarcinogenesisCarcinoma, HepatocellularCell Line, TumorDown-RegulationGene Expression Regulation, NeoplasticHEK293 CellsHumansLeukemia Inhibitory Factor Receptor alpha SubunitLipocalin-2Liver NeoplasmsMaleMiceMice, Inbred C57BLAntibodies, NeutralizingerastinLCN2 protein, humanLeukemia Inhibitory Factor Receptor alpha SubunitLIFR protein, humanLipocalin-2NF-kappa BPiperazinesProtein Tyrosine Phosphatase, Non-Receptor Type 6PTPN6 protein, humanSorafenib

Identifiers

PMID34921145
PMCPMC8683481
OpenAlexW4200614050

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.