Evidence map›Paper›PMID 22457358›Full record

Trial reportThe Journal of biological chemistry2012

α2β1 integrin promotes chemoresistance against doxorubicin in cancer cells through extracellular signal-regulated kinase (ERK).

Dalila Naci, Mohammed-Amine El Azreq, Nizar Chetoui, Laura Lauden, François Sigaux, Dominique Charron, Reem Al-Daccak, Fawzi Aoudjit

Open access · hybridAbstract readClinical Trial
In one paragraph

Trial report in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.

0numbers the graph read from it
0cells of the map it votes in
51citing papers in PubMed
4.3field-weighted citation impact, top 5% 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

51 citing papers in PubMed, 101 citations in OpenAlex.

  1. Article
  2. Goodbye flat lymphoma biology.FEBS letters · 2025
    Review
  3. Article
  4. Article
  5. Focus on Pancreatic Cancer Microenvironment.Current oncology (Toronto, Ont.) · 2024
    Review
  6. Review
  7. Review
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  9. Article
  10. Three-dimensional models: a novel approach for lymphoma research.Journal of cancer research and clinical oncology · 2022
    Review
  11. Article
  12. Review
  13. Article
  14. Article
  15. Article
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  17. Review
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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

8 authors at 4 institutions in 2 countries.

Dalila NaciCentre de Recherche en Rhumatologie/Immunologie, Centre Hospitalier Universitaire de Québec, Pavillon CHUL, and Faculté de Médecine, Université Laval, 2705 Boulevard Laurier, Local T1-49, Québec G1V4G2, Canada.
Mohammed-Amine El AzreqCentre de Recherche en Rhumatologie/Immunologie, Centre Hospitalier Universitaire de Québec, Pavillon CHUL, and Faculté de Médecine, Université Laval, 2705 Boulevard Laurier, Local T1-49, Québec G1V4G2, Canada.
Nizar ChetouiCentre de Recherche en Rhumatologie/Immunologie, Centre Hospitalier Universitaire de Québec, Pavillon CHUL, and Faculté de Médecine, Université Laval, 2705 Boulevard Laurier, Local T1-49, Québec G1V4G2, Canada.
Laura LaudenInstitut National de la Santé et de la Recherche Médicale (INSERM) UMRS 940, Institut Universitaire d'Hématologie Université Paris Denis Diderot, Hôpital Saint Louis, 75010 Paris, France.
François SigauxINSERM U944, Institut Universitaire d'Hématologie Université Paris Denis Diderot, Hôpital Saint Louis, 75010 Paris, France.
Dominique CharronInstitut National de la Santé et de la Recherche Médicale (INSERM) UMRS 940, Institut Universitaire d'Hématologie Université Paris Denis Diderot, Hôpital Saint Louis, 75010 Paris, France.
Reem Al-DaccakInstitut National de la Santé et de la Recherche Médicale (INSERM) UMRS 940, Institut Universitaire d'Hématologie Université Paris Denis Diderot, Hôpital Saint Louis, 75010 Paris, France.
Fawzi AoudjitCentre de Recherche en Rhumatologie/Immunologie, Centre Hospitalier Universitaire de Québec, Pavillon CHUL, and Faculté de Médecine, Université Laval, 2705 Boulevard Laurier, Local T1-49, Québec G1V4G2, Canada. Electronic address: fawzi.aoudjit@crchul.ulaval.ca.
Centre hospitalier universitaire de Québec · CAHôpital Saint-Louis · FRUniversité Laval · CAUniversité Paris Cité · FR

Funding

Canadian Institutes of Health Research MOP-98005
6 · The paper itself

Abstract

The role and the mechanisms by which β1 integrins regulate the survival and chemoresistance of T cell acute lymphoblastic leukemia (T-ALL) still are poorly addressed. In this study, we demonstrate in T-ALL cell lines and primary blasts, that engagement of α2β1 integrin with its ligand collagen I (ColI), reduces doxorubicin-induced apoptosis, whereas fibronectin (Fn) had no effect. ColI but not Fn inhibited doxorubicin-induced mitochondrial depolarization, cytochrome c release, and activation of caspase-9 and -3. ColI but not Fn also prevented doxorubicin from down-regulating the levels of the prosurvival Bcl-2 protein family member Mcl-1. The effect of ColI on Mcl-1 occurred through the inhibition of doxorubicin-induced activation of c-Jun N-terminal kinase (JNK). Mcl-1 knockdown experiments showed that the maintenance of Mcl-1 levels is essential for ColI-mediated T-ALL cell survival. Furthermore, activation of MAPK/ERK, but not PI3K/AKT, is required for ColI-mediated inhibition of doxorubicin-induced JNK activation and apoptosis and for ColI-mediated maintenance of Mcl-1 levels. Thus, our study identifies α2β1 integrin as an important survival pathway in drug-induced apoptosis of T-ALL cells and suggests that its activation can contribute to the generation of drug resistance.

Indexed as

Drug Resistance, NeoplasmAntibiotics, AntineoplasticCaspase 3Caspase 9Collagen Type ICytochromes cDoxorubicinEnzyme ActivationExtracellular Signal-Regulated MAP KinasesFemaleFibronectinsGene Knockdown TechniquesHumansIntegrin alpha2beta1JNK Mitogen-Activated Protein KinasesJurkat CellsAntibiotics, AntineoplasticCASP3 protein, humanCaspase 3Caspase 9Collagen Type ICytochromes cDoxorubicinExtracellular Signal-Regulated MAP KinasesFibronectinsIntegrin alpha2beta1JNK Mitogen-Activated Protein KinasesMyeloid Cell Leukemia Sequence 1 ProteinPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktProto-Oncogene Proteins c-bcl-2

Identifiers

PMID22457358
PMCPMC3366820
OpenAlexW2017589730

What OpenQuestion holds

Textmetadata
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.