Evidence map›Paper›PMID 31476112›Full record

ArticleEMBO molecular medicine2019

A genome-wide RNAi screen reveals essential therapeutic targets of breast cancer stem cells.

Abir Arfaoui, Claire Rioualen, Violette Azzoni, Guillaume Pinna, Pascal Finetti, Julien Wicinski, Emmanuelle Josselin, Manon Macario, Rémy Castellano, Candi Léonard-Stumpf and 11 more

Abstract read
In one paragraph

Article in EMBO molecular medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
–field-weighted citation impact
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

26 citing papers in PubMed.

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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

21 authors.

Abir ArfaouiInserm, CNRS, Institut Paoli-Calmettes, CRCM, Epithelial Stem Cells and Cancer Lab, Aix-Marseille Univ, Marseille, France.
Claire RioualenInserm, CNRS, Institut Paoli-Calmettes, CRCM, Plateform Integrative Bioinformatics, Cibi, Aix-Marseille Univ, Marseille, France.
Violette AzzoniInserm, CNRS, Institut Paoli-Calmettes, CRCM, Epithelial Stem Cells and Cancer Lab, Aix-Marseille Univ, Marseille, France.
Guillaume PinnaPlateforme ARN Interférence, Service de Biologie Intégrative et de Génétique Moléculaire (SBIGeM), I2BC, CEA, CNRS, Université Paris-Saclay, Gif-sur-Yvette, France.
Pascal FinettiInserm, CNRS, Institut Paoli-Calmettes, CRCM, Molecular Oncology "Equipe labellisée Ligue Contre le Cancer", Aix-Marseille Univ, Marseille, France.
Julien WicinskiInserm, CNRS, Institut Paoli-Calmettes, CRCM, Epithelial Stem Cells and Cancer Lab, Aix-Marseille Univ, Marseille, France.
Emmanuelle JosselinInserm, CNRS, Institut Paoli-Calmettes, CRCM, TrGET Plateform, Aix-Marseille Univ, Marseille, France.
Manon MacarioInserm, CNRS, Institut Paoli-Calmettes, CRCM, Epithelial Stem Cells and Cancer Lab, Aix-Marseille Univ, Marseille, France.
Rémy CastellanoInserm, CNRS, Institut Paoli-Calmettes, CRCM, TrGET Plateform, Aix-Marseille Univ, Marseille, France.
Candi Léonard-StumpfInserm, CNRS, Institut Paoli-Calmettes, CRCM, Epithelial Stem Cells and Cancer Lab, Aix-Marseille Univ, Marseille, France.
Anthony BalInserm, CNRS, Institut Paoli-Calmettes, CRCM, Epithelial Stem Cells and Cancer Lab, Aix-Marseille Univ, Marseille, France.
Abigaelle GrosInserm, CNRS, Institut Paoli-Calmettes, CRCM, Epithelial Stem Cells and Cancer Lab, Aix-Marseille Univ, Marseille, France.
Sylvain LossyPlateforme ARN Interférence, Service de Biologie Intégrative et de Génétique Moléculaire (SBIGeM), I2BC, CEA, CNRS, Université Paris-Saclay, Gif-sur-Yvette, France.
Maher KharratFaculté de Médecine de Tunis, LR99ES10 Laboratoire de Génétique Humaine, Université de Tunis El Manar, Tunis, Tunisia.
Yves ColletteInserm, CNRS, Institut Paoli-Calmettes, CRCM, TrGET Plateform, Aix-Marseille Univ, Marseille, France.
Francois BertucciInserm, CNRS, Institut Paoli-Calmettes, CRCM, Molecular Oncology "Equipe labellisée Ligue Contre le Cancer", Aix-Marseille Univ, Marseille, France.
Daniel BirnbaumInserm, CNRS, Institut Paoli-Calmettes, CRCM, Molecular Oncology "Equipe labellisée Ligue Contre le Cancer", Aix-Marseille Univ, Marseille, France.
Hayet DouikFaculté de Médecine de Tunis, LR99ES10 Laboratoire de Génétique Humaine, Université de Tunis El Manar, Tunis, Tunisia.
Ghislain BidautInserm, CNRS, Institut Paoli-Calmettes, CRCM, Plateform Integrative Bioinformatics, Cibi, Aix-Marseille Univ, Marseille, France.
Emmanuelle Charafe-JauffretInserm, CNRS, Institut Paoli-Calmettes, CRCM, Epithelial Stem Cells and Cancer Lab, Aix-Marseille Univ, Marseille, France.
Christophe GinestierInserm, CNRS, Institut Paoli-Calmettes, CRCM, Epithelial Stem Cells and Cancer Lab, Aix-Marseille Univ, Marseille, France.ORCID 0000-0002-7477-3837

Funding

Institut National Du Cancer (INCa) INCa_5911Institut National Du Cancer (INCa) INCa-DGOS-Inserm 6038Ligue Contre le Cancer (Label DB)
6 · The paper itself

Abstract

Therapeutic resistance is a major clinical challenge in oncology. Evidence identifies cancer stem cells (CSCs) as a driver of tumor evolution. Accordingly, the key stemness property unique to CSCs may represent a reservoir of therapeutic target to improve cancer treatment. Here, we carried out a genome-wide RNA interference screen to identify genes that regulate breast CSCs-fate (bCSC). Using an interactome/regulome analysis, we integrated screen results in a functional mapping of the CSC-related processes. This network analysis uncovered potential therapeutic targets controlling bCSC-fate. We tested a panel of 15 compounds targeting these regulators. We showed that mifepristone, salinomycin, and JQ1 represent the best anti-bCSC activity. A combination assay revealed a synergistic interaction of salinomycin/JQ1 association to deplete the bCSC population. Treatment of primary breast cancer xenografts with this combination reduced the tumor-initiating cell population and limited metastatic development. The clinical relevance of our findings was reinforced by an association between the expression of the bCSC-related networks and patient prognosis. Targeting bCSCs with salinomycin/JQ1 combination provides the basis for a new therapeutic approach in the treatment of breast cancer.

Indexed as

RNA InterferenceAntineoplastic AgentsBreast NeoplasmsDrug DiscoveryFemaleGene Regulatory NetworksGenetic TestingGenome-Wide Association StudyHumansNeoplastic Stem CellsProtein Interaction MapsTumor Cells, CulturedAntineoplastic Agentsbreast cancercancer stem cellsJQ1RNAi screensalinomycin

Identifiers

PMID31476112
PMCPMC6783652

What OpenQuestion holds

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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.