Evidence map›Paper›PMID 38092743›Full record

ArticleCell death & disease2023

Hypoxia-induced activation of NDR2 underlies brain metastases from Non-Small Cell Lung Cancer.

Jérôme Levallet, Tiphaine Biojout, Céline Bazille, Manon Douyère, Fatéméh Dubois, Dimitri Leite Ferreira, Jasmine Taylor, Sylvain Teulier, Jérôme Toutain, Nicolas Elie and 4 more

Open access · goldAbstract read
In one paragraph

Article in Cell death & disease, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
2.5field-weighted citation impact, top 11% 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

7 citing papers in PubMed, 12 citations in OpenAlex.

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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

14 authors at 2 institutions in 1 country.

Jérôme LevalletUniversité de Caen Normandie, CNRS, Normandie Université, ISTCT UMR6030, GIP CYCERON, Caen, F-14074, France.ORCID 0000-0003-4133-2813
Tiphaine BiojoutUniversité de Caen Normandie, CNRS, Normandie Université, ISTCT UMR6030, GIP CYCERON, Caen, F-14074, France.
Céline BazilleUniversité de Caen Normandie, CNRS, Normandie Université, ISTCT UMR6030, GIP CYCERON, Caen, F-14074, France.
Manon DouyèreUniversité de Caen Normandie, CNRS, Normandie Université, ISTCT UMR6030, GIP CYCERON, Caen, F-14074, France.
Fatéméh DuboisUniversité de Caen Normandie, CNRS, Normandie Université, ISTCT UMR6030, GIP CYCERON, Caen, F-14074, France.ORCID 0000-0002-1148-7497
Dimitri Leite FerreiraUniversité de Caen Normandie, CNRS, Normandie Université, ISTCT UMR6030, GIP CYCERON, Caen, F-14074, France.
Jasmine TaylorUniversité de Caen Normandie, CNRS, Normandie Université, ISTCT UMR6030, GIP CYCERON, Caen, F-14074, France.
Sylvain TeulierUniversité de Caen Normandie, CNRS, Normandie Université, ISTCT UMR6030, GIP CYCERON, Caen, F-14074, France.
Jérôme ToutainCNRS, Université de Caen Normandie, Normandie Université, ISTCT UMR6030, GIP CYCERON, Caen, F-14074, France.
Nicolas ElieNormandie Univ, UNICAEN, Federative Structure 4207 "Normandie Oncologie", Service Unit PLATON, Virtual'His platform, Caen, France; Normandie Univ, UNICAEN, Service Unit EMERODE, Centre de Microscopie Appliquée à la Biologie, CMABio³, Caen, France.
Myriam BernaudinCNRS, Université de Caen Normandie, Normandie Université, ISTCT UMR6030, GIP CYCERON, Caen, F-14074, France.
Samuel ValableCNRS, Université de Caen Normandie, Normandie Université, ISTCT UMR6030, GIP CYCERON, Caen, F-14074, France.ORCID 0000-0003-0355-0270
Emmanuel BergotUniversité de Caen Normandie, CNRS, Normandie Université, ISTCT UMR6030, GIP CYCERON, Caen, F-14074, France.
Guénaëlle LevalletUniversité de Caen Normandie, CNRS, Normandie Université, ISTCT UMR6030, GIP CYCERON, Caen, F-14074, France. guenaelle.levallet@unicaen.fr.ORCID 0000-0001-7772-0581
Centre National de la Recherche Scientifique · FRNormandie Université · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The molecular mechanisms induced by hypoxia are misunderstood in non-small cell lung cancer (NSCLC), and above all the hypoxia and RASSF1A/Hippo signaling relationship. We confirmed that human NSCLC (n = 45) as their brain metastases (BM) counterpart are hypoxic since positive with CAIX-antibody (target gene of Hypoxia-inducible factor (HIF)). A severe and prolonged hypoxia (0.2% O2, 48 h) activated YAP (but not TAZ) in Human Bronchial Epithelial Cells (HBEC) lines by downregulating RASSF1A/kinases Hippo (except for NDR2) regardless their promoter methylation status. Subsequently, the NDR2-overactived HBEC cells exacerbated a HIF-1A, YAP and C-Jun-dependent-amoeboid migration, and mainly, support BM formation. Indeed, NDR2 is more expressed in human tumor of metastatic NSCLC than in human localized NSCLC while NDR2 silencing in HBEC lines (by shRNA) prevented the xenograft formation and growth in a lung cancer-derived BM model in mice. Collectively, our results indicated that NDR2 kinase is over-active in NSCLC by hypoxia and supports BM formation. NDR2 expression is thus a useful biomarker to predict the metastases risk in patients with NSCLC, easily measurable routinely by immunohistochemistry on tumor specimens.

Indexed as

Brain NeoplasmsCarcinoma, Non-Small-Cell LungLung NeoplasmsAnimalsCell Line, TumorEpithelial CellsHumansHypoxiaHypoxia-Inducible Factor 1, alpha SubunitMiceProtein Serine-Threonine KinasesHypoxia-Inducible Factor 1, alpha SubunitProtein Serine-Threonine KinasesSTK38L protein, human

Identifiers

PMID38092743
PMCPMC10719310
OpenAlexW4389668947

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.