Evidence map›Paper›PMID 39023520›Full record

ArticleeLife2024

Netrin signaling mediates survival of dormant epithelial ovarian cancer cells.

Pirunthan Perampalam, James I MacDonald, Komila Zakirova, Daniel T Passos, Sumaiyah Wasif, Yudith Ramos-Valdes, Maeva Hervieu, Patrick Mehlen, Rob Rottapel, Benjamin Gibert and 3 more

Abstract read
In one paragraph

Article in eLife, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed, 1 pooled it
–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

6 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Article
  4. Review
  5. Research progress of the netrins and their receptors in cancer.Journal of cellular and molecular medicine · 2024
    Review
  6. 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.

Pirunthan PerampalamLondon Regional Cancer Program, London Health Sciences Centre Research Institute, London, Canada.
James I MacDonaldLondon Regional Cancer Program, London Health Sciences Centre Research Institute, London, Canada.
Komila ZakirovaLondon Regional Cancer Program, London Health Sciences Centre Research Institute, London, Canada.
Daniel T PassosLondon Regional Cancer Program, London Health Sciences Centre Research Institute, London, Canada.ORCID https://orcid.org/0000-0002-3530-2821
Sumaiyah WasifLondon Regional Cancer Program, London Health Sciences Centre Research Institute, London, Canada.
Yudith Ramos-ValdesLondon Regional Cancer Program, London Health Sciences Centre Research Institute, London, Canada.
Maeva HervieuApoptosis, Cancer and Development Laboratory - Equipe labellisée 'La Ligue', LabEx DEVweCAN, Institut Convergence PLAsCAN, Centre de Recherche en Cancérologie de Lyon (CRCL), INSERM U1052-CNRS UMR5286, Université de Lyon, Université Claude Bernard Lyon1, Centre Léon Bérard, Lyon, France.
Patrick MehlenApoptosis, Cancer and Development Laboratory - Equipe labellisée 'La Ligue', LabEx DEVweCAN, Institut Convergence PLAsCAN, Centre de Recherche en Cancérologie de Lyon (CRCL), INSERM U1052-CNRS UMR5286, Université de Lyon, Université Claude Bernard Lyon1, Centre Léon Bérard, Lyon, France.
Rob RottapelPrincess Margaret Cancer Centre, University Health Network, Toronto, Canada.
Benjamin GibertApoptosis, Cancer and Development Laboratory - Equipe labellisée 'La Ligue', LabEx DEVweCAN, Institut Convergence PLAsCAN, Centre de Recherche en Cancérologie de Lyon (CRCL), INSERM U1052-CNRS UMR5286, Université de Lyon, Université Claude Bernard Lyon1, Centre Léon Bérard, Lyon, France.ORCID https://orcid.org/0000-0002-5295-3124
Rohann J M CorreaLondon Regional Cancer Program, London Health Sciences Centre Research Institute, London, Canada.
Trevor G ShepherdLondon Regional Cancer Program, London Health Sciences Centre Research Institute, London, Canada.
Frederick A DickLondon Regional Cancer Program, London Health Sciences Centre Research Institute, London, Canada.ORCID https://orcid.org/0000-0002-0047-9985

Funding

Cancer Research Society 23150Cancer Research Society 25021CIHR PJT173391Ontario Institute for Cancer Research P.CTIP.966
6 · The paper itself

Abstract

Dormancy in cancer is a clinical state in which residual disease remains undetectable for a prolonged duration. At a cellular level, rare cancer cells cease proliferation and survive chemotherapy and disseminate disease. We created a suspension culture model of high-grade serous ovarian cancer (HGSOC) dormancy and devised a novel CRISPR screening approach to identify survival genes in this context. In combination with RNA-seq, we discovered the Netrin signaling pathway as critical to dormant HGSOC cell survival. We demonstrate that Netrin-1, -3, and its receptors are essential for low level ERK activation to promote survival, and that Netrin activation of ERK is unable to induce proliferation. Deletion of all UNC5 family receptors blocks Netrin signaling in HGSOC cells and compromises viability during the dormancy step of dissemination in xenograft assays. Furthermore, we demonstrate that Netrin-1 and -3 overexpression in HGSOC correlates with poor outcome. Specifically, our experiments reveal that Netrin overexpression elevates cell survival in dormant culture conditions and contributes to greater spread of disease in a xenograft model of abdominal dissemination. This study highlights Netrin signaling as a key mediator HGSOC cancer cell dormancy and metastasis.

Indexed as

Carcinoma, Ovarian EpithelialCell SurvivalNetrinsOvarian NeoplasmsSignal TransductionAnimalsCell Line, TumorCell ProliferationFemaleHumansMiceNetrin-1Netrin ReceptorsNetrin-1Netrin ReceptorsNetrinsNTN1 protein, humancancer biologydormancyDyrk1ahigh grade serous ovarian cancermouseNetrinquiescencespheroids

Identifiers

PMID39023520
PMCPMC11257678

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.