Evidence map›Paper›PMID 28202042›Full record

ArticleMolecular cancer2017

HOXC8 regulates self-renewal, differentiation and transformation of breast cancer stem cells.

Mansi Shah, Ryan Cardenas, Belinda Wang, Jenny Persson, Nigel P Mongan, Anna Grabowska, Cinzia Allegrucci

Open access · goldAbstract read
In one paragraph

Article in Molecular cancer, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
2.7field-weighted citation impact, top 9% 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

31 citing papers in PubMed, 56 citations in OpenAlex.

  1. Review
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  7. Association ofGenes · 2022
    Article
  8. Article
  9. Tumour Stem Cells in Breast Cancer.International journal of molecular sciences · 2022
    Review
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  14. Observational
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  20. Methylation inCells · 2020
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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

7 authors at 2 institutions in 3 countries.

Mansi ShahSVMS, University of Nottingham, Sutton Bonington Campus, Loughborough, LE12 5RD, UK.
Ryan CardenasSVMS, University of Nottingham, Sutton Bonington Campus, Loughborough, LE12 5RD, UK.
Belinda WangSVMS, University of Nottingham, Sutton Bonington Campus, Loughborough, LE12 5RD, UK.
Jenny PerssonDepartment of Translational Medicine, Lund University, Malmö, 205 02, Sweden.
Nigel P MonganSVMS, University of Nottingham, Sutton Bonington Campus, Loughborough, LE12 5RD, UK.
Anna GrabowskaCancer Biology, Division of Cancer and Stem Cells, School of Medicine, University of Nottingham, QMC, Nottingham, NG7 2UH, UK.
Cinzia AllegrucciSVMS, University of Nottingham, Sutton Bonington Campus, Loughborough, LE12 5RD, UK. cinzia.allegrucci@nottingham.ac.uk.ORCID 0000-0001-8517-2423
University of Nottingham · GBLund University · SE

Funding

Biotechnology and Biological Sciences Research Council RS4949
6 · The paper itself

Abstract

backgroundHomeobox genes are master regulators of cell fate during embryonic development and their expression is altered in cancer. By regulating the balance between cell proliferation and differentiation, they maintain homeostasis of normal tissues. Here, we screened the expression of homeobox genes in mammary stem cells to establish their role in stem cells transformation in breast cancer.

methodsUsing a Homeobox Genes PCR array, we screened 83 homeobox genes in normal cancer breast stem/progenitor cells isolated by flow cytometry. The candidate gene HOXC8 epigenetic regulation was studied by DNA methylation and miRNA expression analyses. Self-renewal and differentiation of HOXC8-overexpressing or knockdown cells were assessed by flow cytometry and mammosphere, 3D matrigel and soft agar assays. Clinical relevance of in vitro findings were validated by bioinformatics analysis of patient datasets from TCGA and METABRIC studies.

resultsIn this study we demonstrate altered expression of homeobox genes in breast cancer stem/progenitor cells. HOXC8 was consistently downregulated in stem/progenitor cells of all breast molecular subtypes, thus representing an interesting tumour suppressor candidate. We show that downregulated expression of HOXC8 is associated with DNA methylation at the gene promoter and expression of miR196 family members. Functional studies demonstrated that HOXC8 gain of function induces a decrease in the CD44

conclusionsTaken together, our study points to an important role of homeobox genes in breast cancer stem/progenitor cell function and establishes HOXC8 as a suppressor of stemness and transformation in the mammary gland lineage.

Indexed as

Breast NeoplasmsCell DifferentiationCell Line, TumorDNA MethylationDown-RegulationDrug Resistance, NeoplasmEpigenesis, GeneticFemaleGene Expression Regulation, NeoplasticHomeodomain ProteinsHumansMCF-7 CellsMicroRNAsNeoplastic Stem CellsPromoter Regions, GeneticHomeodomain ProteinsHOXC8 protein, humanMicroRNAsMIRN196 microRNA, humanBreast cancerCancer stem cellsDifferentiationHomeobox genesHOXC8Self-renewal

Identifiers

PMID28202042
PMCPMC5312582
OpenAlexW2587869120

What OpenQuestion holds

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LicenceCC BY
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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.