Evidence map›Paper›PMID 26675549›Full record

ArticleOncotarget2016

Artemin is hypoxia responsive and promotes oncogenicity and increased tumor initiating capacity in hepatocellular carcinoma.

Min Zhang, Weijie Zhang, Zhengsheng Wu, Shumin Liu, Linchong Sun, Yanghao Zhong, Xiao Zhang, Xiangjun Kong, Pengxu Qian, Huafeng Zhang and 2 more

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

Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
1.5field-weighted citation impact, top 19% 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

20 citing papers in PubMed, 33 citations in OpenAlex.

  1. Circulating Back to Blood: Erythrocyte Precursors Put the Brakes on Acute Lung Injury.American journal of respiratory cell and molecular biology · 2025
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  15. The GDNF Family: A Role in Cancer?Neoplasia (New York, N.Y.) · 2018
    Review
  16. Article
  17. Article
  18. Artemin promotes proliferation and metastasis in human laryngeal squamous cell carcinoma.International journal of clinical and experimental pathology · 2017
    Article
  19. Review
  20. Article
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

12 authors at 3 institutions in 2 countries.

Min ZhangThe CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, China.
Weijie ZhangThe CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, China.
Zhengsheng WuDepartment of Pathology, Anhui Medical University, Hefei, China.
Shumin LiuThe CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, China.
Linchong SunThe CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, China.
Yanghao ZhongThe CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, China.
Xiao ZhangThe CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, China.
Xiangjun KongThe CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, China.
Pengxu QianThe CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, China.
Huafeng ZhangThe CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, China.
Peter E LobieCancer Science Institute of Singapore and Department of Pharmacology, National University of Singapore, Singapore.
Tao ZhuThe CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, China.
University of Science and Technology of China · CNHefei National Center for Physical Sciences at Nanoscale · CNNational University Cancer Institute, Singapore · SG

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Hypoxia has been reported to regulate the cancer stem cell (CSC) population yet the underlying mechanism is poorly characterized. Herein, we show that Artemin (ARTN), a member of the glial cell derived neurotrophic factor family of ligands, is a hypoxia-responsive factor and is essential for hypoxia-induced CSC expansion in hepatocellular carcinoma (HCC). Clinically, elevated expression of ARTN in HCC was associated with larger tumor size, faster relapse and shorter survival. In vitro, HCC cells with forced expression of ARTN exhibited reduced apoptosis, increased proliferation, epithelial-mesenchymal transition (EMT) and enhanced motility. Additionally, ARTN dramatically increased xenograft tumor size and metastasis in vivo. Moreover, ARTN also enhanced tumorsphere formation and the tumor initiating capacity of HCC cells, consequent to expansion of the CD133+ CSC population. ARTN transcription was directly activated by hypoxia-induced factor-1α (HIF-1α) and hypoxia induced ARTN promoted EMT and increased the CSC population via AKT signaling. We herein identify a novel HIF-1α/ARTN axis promoting CSC-like behavior in hypoxic environments which implicates ARTN as a valuable therapeutic target for HCC.

Indexed as

Epithelial-Mesenchymal TransitionAnimalsApoptosisCarcinoma, HepatocellularCell ProliferationCell Transformation, NeoplasticFluorescent Antibody TechniqueHumansHypoxiaHypoxia-Inducible Factor 1, alpha SubunitImmunoenzyme TechniquesLiver NeoplasmsMaleMiceMice, Inbred BALB CMice, NudeARTN protein, humanHIF1A protein, humanHypoxia-Inducible Factor 1, alpha SubunitNerve Tissue ProteinsRNA, MessengerARTNcancer stem cellhepatocellular carcinomahypoxia

Identifiers

PMID26675549
PMCPMC4823105
OpenAlexW2217240615

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.