Evidence map›Paper›PMID 24229464›Full record

ArticleBreast cancer research : BCR2013

A mammosphere formation RNAi screen reveals that ATG4A promotes a breast cancer stem-like phenotype.

Jonas Wolf, Dyah Laksmi Dewi, Johannes Fredebohm, Karin Müller-Decker, Christa Flechtenmacher, Jörg D Hoheisel, Michael Boettcher

Open access · goldAbstract read
In one paragraph

Article in Breast cancer research : BCR, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.

0numbers the graph read from it
0cells of the map it votes in
82citing papers in PubMed
3.0field-weighted citation impact, top 8% 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

82 citing papers in PubMed, 132 citations in OpenAlex.

  1. Review
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  6. Autophagy Protease ATG4D Facilitates Proliferation and Malignancy of Osteosarcoma Cells.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025
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  10. The IPBiochimica et biophysica acta. Molecular basis of disease · 2025
    Article
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  12. Autophagy and cancer therapy.Cancer letters · 2024
    Review
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  17. Article
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22 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

7 authors at 3 institutions in 1 country.

Jonas Wolf
Dyah Laksmi Dewi
Johannes Fredebohm
Karin Müller-Decker
Christa Flechtenmacher
Jörg D Hoheisel
Michael Boettcher
German Cancer Research Center · DEDKFZ-ZMBH Alliance · DEUniversity Hospital Heidelberg · DE

Funding

Algorithm and genome-wide database of functional siRNAsR44HG003355 · NHGRI · CELLECTA, INC. · PI CHENCHIK, ALEX · 2007 to 2009
$2.5M
Functionally Validated Lentiviral siRNA librariesR44RR024095 · NCRR · CELLECTA, INC. · PI CHENCHIK, ALEX · 2010 to 2011
$1.9M
Functionally Validated Lentiviral siRNA LibrariesR43RR024095 · NCRR · CELLECTA, INC. · PI CHENCHIK, ALEX · 2007 to 2007
$289k
Algorithm and genome-wide database of functional siRNAsR43HG003355 · NHGRI · SYSTEM BIOSCIENCES, LLC (SBI) · PI CHENCHIK, ALEX · 2004 to 2004
$100k
NCRR NIH HHS 44RR024095NHGRI NIH HHS 44HG003355
6 · The paper itself

Abstract

introductionBreast cancer stem cells are suspected to be responsible for tumour recurrence, metastasis formation as well as chemoresistance. Consequently, great efforts have been made to understand the molecular mechanisms underlying cancer stem cell maintenance. In order to study these rare cells in-vitro, they are typically enriched via mammosphere culture. Here we developed a mammosphere-based negative selection shRNAi screening system suitable to analyse the involvement of thousands of genes in the survival of cells with cancer stem cell properties.

methodsWe describe a sub-population expressing the stem-like marker CD44(+)/CD24(-/low) in SUM149 that were enriched in mammospheres. To identify genes functionally involved in the maintenance of the sub-population with cancer stem cell properties, we targeted over 5000 genes by RNAi and tested their ability to grow as mammospheres. The identified candidate ATG4A was validated in mammosphere and soft agar colony formation assays. Further, we evaluated the influence of ATG4A expression on the sub-population expressing the stem-like marker CD44(+)/CD24(low). Next, the tumorigenic potential of SUM149 after up- or down-regulation of ATG4A was examined by xenograft experiments.

resultsUsing this method, Jak-STAT as well as cytokine signalling were identified to be involved in mammosphere formation. Furthermore, the autophagy regulator ATG4A was found to be essential for the maintenance of a sub-population with cancer stem cell properties and to regulate breast cancer cell tumourigenicity in vivo.

conclusionIn summary, we present a high-throughput screening system to identify genes involved in cancer stem cell maintenance and demonstrate its utility by means of ATG4A.

Indexed as

AnimalsAutophagy-Related ProteinsBreast NeoplasmsCD24 AntigenCell Culture TechniquesCysteine EndopeptidasesFemaleGene Expression Regulation, NeoplasticHigh-Throughput Screening AssaysHumansHyaluronan ReceptorsMice, SCIDNeoplastic Stem CellsOxidative PhosphorylationPhenotypeReproducibility of ResultsATG4A protein, humanAutophagy-Related ProteinsCD24 AntigenCD24 protein, humanCD44 protein, humanCysteine EndopeptidasesHyaluronan Receptors

Identifiers

PMID24229464
PMCPMC3978845
OpenAlexW2114957557

What OpenQuestion holds

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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.