Evidence map›Paper›PMID 30979377›Full record

ArticleJournal of experimental & clinical cancer research : CR2019

NDR2 kinase contributes to cell invasion and cytokinesis defects induced by the inactivation of RASSF1A tumor-suppressor gene in lung cancer cells.

Maureen Keller, Fatéméh Dubois, Sylvain Teulier, Alexandre P J Martin, Jérôme Levallet, Elodie Maille, Solenn Brosseau, Nicolas Elie, Alexander Hergovich, Emmanuel Bergot and 3 more

Open access · goldAbstract read
In one paragraph

Article in Journal of experimental & clinical cancer research : CR, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
1.8field-weighted citation impact, top 17% 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

24 citing papers in PubMed, 32 citations in OpenAlex.

  1. Article
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  6. The NDR family of kinases: essential regulators of aging.Frontiers in molecular neuroscience · 2024
    Review
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  8. Article
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  13. The Diagnostic Potential ofFrontiers in oncology · 2022
    Article
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  15. Article
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  17. The STK38-XPO1 axis, a new actor in physiology and cancer.Cellular and molecular life sciences : CMLS · 2021
    Review
  18. Review
  19. Article
  20. Article
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

13 authors at 5 institutions in 2 countries.

Maureen KellerNormandie University, UNICAEN, UMR 1086 INSERM, F-14032, Caen, France.
Fatéméh DuboisNormandie University, UNICAEN, CEA, CNRS, ISTCT/CERVOxy group, GIP CYCERON, Avenue H.Becquerel- 14074, F-14000, Caen, France.
Sylvain TeulierNormandie University, UNICAEN, CEA, CNRS, ISTCT/CERVOxy group, GIP CYCERON, Avenue H.Becquerel- 14074, F-14000, Caen, France.
Alexandre P J MartinU830 INSERM, "Génétique et Biologie des cancers" Centre de Recherche, Institut Curie, Paris, France.
Jérôme LevalletNormandie University, UNICAEN, UPRES-EA-2608, F-14032, Caen, France.
Elodie MailleNormandie University, UNICAEN, UMR 1086 INSERM, F-14032, Caen, France.
Solenn BrosseauNormandie University, UNICAEN, UMR 1086 INSERM, F-14032, Caen, France.
Nicolas ElieNormandie Univ, UNICAEN, SFR ICORE, Plateau CMABio3, F-14032, Caen, France.
Alexander HergovichUniversity College London Cancer Institute, WC1E 6BT, London, UK.
Emmanuel BergotNormandie University, UNICAEN, CEA, CNRS, ISTCT/CERVOxy group, GIP CYCERON, Avenue H.Becquerel- 14074, F-14000, Caen, France.
Jacques CamonisU830 INSERM, "Génétique et Biologie des cancers" Centre de Recherche, Institut Curie, Paris, France.
Gérard ZalcmanU830 INSERM, "Génétique et Biologie des cancers" Centre de Recherche, Institut Curie, Paris, France.
Guénaëlle LevalletNormandie University, UNICAEN, CEA, CNRS, ISTCT/CERVOxy group, GIP CYCERON, Avenue H.Becquerel- 14074, F-14000, Caen, France. guenaelle.levallet@unicaen.fr.
Inserm · FRCentre National de la Recherche Scientifique · FRNormandie Université · FRCentre Hospitalier Universitaire de Caen Normandie · FRLondon Cancer · GB

Funding

Ligue Contre le Cancer 2012Ligue Contre le Cancer 2016
6 · The paper itself

Abstract

backgroundRASSF1A, a tumor suppressor gene, is frequently inactivated in lung cancer leading to a YAP-dependent epithelial-mesenchymal transition (EMT). Such effects are partly due to the inactivation of the anti-migratory RhoB GTPase via the inhibitory phosphorylation of GEF-H1, the GDP/GTP exchange factor for RhoB. However, the kinase responsible for RhoB/GEF-H1 inactivation in RASSF1A-depleted cells remained unknown.

methodsNDR1/2 inactivation by siRNA or shRNA effects on epithelial-mesenchymal transition, invasion, xenograft formation and growth in SCID-/- Beige mice, apoptosis, proliferation, cytokinesis, YAP/TAZ activation were investigated upon RASSF1A loss in human bronchial epithelial cells (HBEC).

resultsWe demonstrate here that depletion of the YAP-kinases NDR1/2 reverts migration and metastatic properties upon RASSF1A loss in HBEC. We show that NDR2 interacts directly with GEF-H1 (which contains the NDR phosphorylation consensus motif HXRXXS/T), leading to GEF-H1 phosphorylation. We further report that the RASSF1A/NDR2/GEF-H1/RhoB/YAP axis is involved in proper cytokinesis in human bronchial cells, since chromosome proper segregation are NDR-dependent upon RASSF1A or GEF-H1 loss in HBEC.

conclusionTo summarize, our data support a model in which, upon RASSF1A silencing, NDR2 gets activated, phosphorylates and inactivates GEF-H1, leading to RhoB inactivation. This cascade induced by RASSF1A loss in bronchial cells is responsible for metastasis properties, YAP activation and cytokinesis defects.

Indexed as

Gene SilencingGenes, SuppressorAnimalsBiomarkers, TumorCell Cycle ProteinsCell Line, TumorCell MovementCytokinesisDisease Models, AnimalEpithelial-Mesenchymal TransitionHeterograftsHumansLung NeoplasmsMiceNeoplasm MetastasisNuclear ProteinsBiomarkers, TumorCell Cycle ProteinsNuclear ProteinsProtein Serine-Threonine KinasesRASSF1 protein, humanrhoB GTP-Binding ProteinSTK38L protein, humanTranscription FactorsTumor Suppressor ProteinsYY1AP1 protein, humanGEF-H1Lung cancerNDR2 kinaseRASSF1AYAP

Identifiers

PMID30979377
PMCPMC6461807
OpenAlexW2935846858

What OpenQuestion holds

Textmetadata
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.