Evidence map›Paper›PMID 21464043›Full record

ArticleCancer research2011

Does the hepatitis B antigen HBx promote the appearance of liver cancer stem cells?

Alla Arzumanyan, Tiffany Friedman, Irene O L Ng, Marcia M Clayton, Zhaorui Lian, Mark A Feitelson

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

Article in Cancer research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.

0numbers the graph read from it
0cells of the map it votes in
73citing papers in PubMed
3.9field-weighted citation impact, top 6% 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

73 citing papers in PubMed, 114 citations in OpenAlex.

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  12. Short-chain fatty acids in cancer pathogenesis.Cancer metastasis reviews · 2023
    Review
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13 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

6 authors at 3 institutions in 3 countries.

Alla ArzumanyanDepartment of Biology, Sbarro Health Research Organization, College of Science and Technology, Temple University, Philadelphia, Pennsylvania 19122, USA. alla.arzumanyan@temple.edu
Tiffany Friedman
Irene O L Ng
Marcia M Clayton
Zhaorui Lian
Mark A Feitelson
Sbarro Health Research Organization · USQueen Mary Hospital · CNTemple University · US

Funding

Early antibody markers of HCCR01CA111427 · NCI · THOMAS JEFFERSON UNIVERSITY · PI FEITELSON, MARK A · 2005 to 2009
$1.4M
Beta-Catenin Signaling in HBxAg Mediated HCC.R01CA104025 · NCI · THOMAS JEFFERSON UNIVERSITY · PI FEITELSON, MARK A · 2006 to 2010
$1.3M
NCI NIH HHS CA104025NCI NIH HHS CA111427NCI NIH HHS R01 CA104025NCI NIH HHS R01 CA111427
6 · The paper itself

Abstract

Hepatitis B virus (HBV) is a major etiologic agent of chronic liver disease and hepatocellular carcinoma (HCC). HBV-encoded X antigen, HBx, and pathways implicated in the self-renewal of stem cells contribute to HCC, but it is not clear whether HBx expression promotes "stemness." Thus, experiments were designed to test the hypothesis that HBx triggers malignant transformation by promoting properties that are characteristic of cancer stem cells (CSC). To test this hypothesis, HepG2 cells were stably transduced with HBx and then assayed for phenotypic and molecular characteristics of "stemness." The relationship between HBx and "stemness"-associated markers was also evaluated by immunohistochemical staining of liver and tumor tissue sections from HBV-infected patients. The results showed that Oct-4, Nanog, Klf-4, β-catenin, and epithelial cell adhesion molecule (EpCAM) were activated by HBx in vitro and in vivo. EpCAM was detected in the nuclei of human HCC cells from infected patients. HBx promotes "stemness" by activating β-catenin and epigenetic upregulation of miR-181, both of which target EpCAM. HBx expression was also associated with depressed levels of E-cadherin. Moreover, HBx stimulated cell migration, growth in soft agar, and spheroid formation. This work is the first to propose that HBV promotes "stemness" in the pathogenesis of HCC. HBx-associated upregulated expression of multiple "stemness" markers supports the hypothesis that HBx contributes to hepatocarcinogenesis, at least in part, by promoting changes in gene expression that are characteristics of CSCs.

Indexed as

AdultAgedAntigens, Neoplasmbeta CateninCell Adhesion MoleculesCell Line, TumorCell MovementEpigenesis, GeneticEpithelial Cell Adhesion MoleculeFemaleHepatitis B virusHomeodomain ProteinsHumansKruppel-Like Factor 4Kruppel-Like Transcription FactorsLiver NeoplasmsAntigens, Neoplasmbeta CateninCell Adhesion MoleculesEpithelial Cell Adhesion Moleculehepatitis B virus X proteinHomeodomain ProteinsKLF4 protein, humanKruppel-Like Factor 4Kruppel-Like Transcription FactorsNanog Homeobox ProteinNANOG protein, humanOctamer Transcription Factor-3POU5F1 protein, humanTrans-ActivatorsViral Regulatory and Accessory Proteins

Identifiers

PMID21464043
PMCPMC3096741
OpenAlexW1979807911

What OpenQuestion holds

Textmetadata
LicenceTDM
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.