Evidence map›Paper›PMID 25837487›Full record

ArticleCell death & disease2015

In vitro evidence for senescent multinucleated melanocytes as a source for tumor-initiating cells.

C Leikam, A L Hufnagel, C Otto, D J Murphy, B Mühling, S Kneitz, I Nanda, M Schmid, T U Wagner, S Haferkamp and 3 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell death & disease, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed
3.6field-weighted citation impact, top 7% 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

38 citing papers in PubMed, 74 citations in OpenAlex.

  1. Review
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  8. Whole-Genome Doubling as a source of cancer: how, when, where, and why?Frontiers in cell and developmental biology · 2023
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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

13 authors at 5 institutions in 2 countries.

C LeikamDepartment of Physiological Chemistry I, University of Wurzburg, Biocenter, Am Hubland, Wurzburg, Germany.
A L HufnagelDepartment of Physiological Chemistry I, University of Wurzburg, Biocenter, Am Hubland, Wurzburg, Germany.
C OttoExperimental Surgery, Experimental Transplantation Immunology, Clinic of General, Visceral, Vascular and Pediatric Surgery (Surgical Clinic I), University of Wurzburg Hospital, Wurzburg, Germany.
D J MurphyInstitute of Cancer Sciences, Beatson Institute for Cancer Research, University of Glasgow, Glasglow, UK.
B MühlingExperimental Surgery, Experimental Transplantation Immunology, Clinic of General, Visceral, Vascular and Pediatric Surgery (Surgical Clinic I), University of Wurzburg Hospital, Wurzburg, Germany.
S KneitzDepartment of Physiological Chemistry I, University of Wurzburg, Biocenter, Am Hubland, Wurzburg, Germany.
I NandaInstitute for Human Genetics, University of Wurzburg, Biocenter, Am Hubland, Wurzburg, Germany.
M SchmidInstitute for Human Genetics, University of Wurzburg, Biocenter, Am Hubland, Wurzburg, Germany.
T U WagnerDepartment of Physiological Chemistry I, University of Wurzburg, Biocenter, Am Hubland, Wurzburg, Germany.
S HaferkampDepartment of Dermatology, University Hospital Erlangen, Erlangen, Germany.
E-B BröckerDepartment of Dermatology, Venereology and Allergology, University Hospital Wurzburg, Wurzburg, Germany.
M Schartl1] Department of Physiological Chemistry I, University of Wurzburg, Biocenter, Am Hubland, Wurzburg, Germany [2] Comprehensive Cancer Center Mainfranken, University Hospital Wurzburg, Wurzburg, Germany.
S Meierjohann1] Department of Physiological Chemistry I, University of Wurzburg, Biocenter, Am Hubland, Wurzburg, Germany [2] Comprehensive Cancer Center Mainfranken, University Hospital Wurzburg, Wurzburg, Germany.
University of Würzburg · DEUniversitätsklinikum Würzburg · DEComprehensive Cancer Center Mainfranken · DEUniversitätsklinikum Erlangen · DEUniversity of Glasgow · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Oncogenic signaling in melanocytes results in oncogene-induced senescence (OIS), a stable cell-cycle arrest frequently characterized by a bi- or multinuclear phenotype that is considered as a barrier to cancer progression. However, the long-sustained conviction that senescence is a truly irreversible process has recently been challenged. Still, it is not known whether cells driven into OIS can progress to cancer and thereby pose a potential threat. Here, we show that prolonged expression of the melanoma oncogene N-RAS(61K) in pigment cells overcomes OIS by triggering the emergence of tumor-initiating mononucleated stem-like cells from senescent cells. This progeny is dedifferentiated, highly proliferative, anoikis-resistant and induces fast growing, metastatic tumors. Our data describe that differentiated cells, which are driven into senescence by an oncogene, use this senescence state as trigger for tumor transformation, giving rise to highly aggressive tumor-initiating cells. These observations provide the first experimental in vitro evidence for the evasion of OIS on the cellular level and ensuing transformation.

Indexed as

Amino Acid SequenceAnimalsCell ProliferationCellular SenescenceGTP PhosphohydrolasesHeterograftsHumansIn Vitro TechniquesMelanocytesMembrane ProteinsMiceMice, NudeMolecular Sequence DataNeoplastic Stem CellsNevusSignal TransductionGTP PhosphohydrolasesMembrane ProteinsNRAS protein, human

Identifiers

PMID25837487
PMCPMC4650540
OpenAlexW2035460682

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.