Evidence map›Paper›PMID 25659584›Full record

ArticleOncogene2015

A role for Rac1 activity in malignant progression of sebaceous skin tumors.

D Frances, N Sharma, R Pofahl, M Maneck, K Behrendt, K Reuter, T Krieg, C A Klein, I Haase, C Niemann

Abstract read
PubMed Publisher
In one paragraph

Article in Oncogene, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
2.5field-weighted citation impact, top 10% 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

17 citing papers in PubMed, 23 citations in OpenAlex.

  1. Article
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  12. Apoptotic and Nonapoptotic Activities of Pterostilbene against Cancer.International journal of molecular sciences · 2018
    Review
  13. Review
  14. Review
  15. Review
  16. Lrig1 Expression in Human Sebaceous Gland Tumors.Dermatopathology (Basel, Switzerland)
    Article
  17. Review
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

10 authors at 2 institutions in 1 country.

D FrancesCenter for Molecular Medicine Cologne, University of Cologne, Cologne, Germany.
N SharmaCenter for Molecular Medicine Cologne, University of Cologne, Cologne, Germany.
R PofahlDepartment of Dermatology University of Cologne, Cologne, Germany.
M ManeckExperimental Medicine and Therapy Research, University of Regensburg, Cologne, Germany.
K BehrendtDepartment of Dermatology University of Cologne, Cologne, Germany.
K ReuterCenter for Molecular Medicine Cologne, University of Cologne, Cologne, Germany.
T KriegDepartment of Dermatology University of Cologne, Cologne, Germany.
C A KleinExperimental Medicine and Therapy Research, University of Regensburg, Cologne, Germany.
I HaaseDepartment of Dermatology University of Cologne, Cologne, Germany.
C NiemannCenter for Molecular Medicine Cologne, University of Cologne, Cologne, Germany.
University of Cologne · DEUniversity of Regensburg · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The small GTPase Rac1 is crucial for maintaining stem cells (SCs) in mammalian epidermis, and Rac1 activation leads to SC expansion. Loss or inhibition of Rac1 correlates with decreased frequency of skin cancer formation in a chemical carcinogenesis model. Here, we have addressed whether Rac1 activation would enhance carcinogenesis and result in tumor progression. We used K14ΔNLef1 mice, a model for differentiated sebaceous adenomas (SAs), and activated Rac1 in an epidermis-specific manner (K14L61Rac1). Surprisingly, Rac1 activation did not change the incidence and frequency of sebaceous tumors. However, tumors, which occurred exclusively in K14ΔNLef1/K14L61Rac1 double-transgenic mice, were poorly differentiated resembling malignant sebaceous tumors and were termed sebaceous carcinoma-like tumors (SCLTs). Compared with SAs, SCLTs showed an aberrant pattern of cell proliferation, invasive growth and less abundant expression of sebocyte differentiation markers, including stearoyl-CoA desaturase-1 and adipophilin. Interestingly, the adnexal SC marker Lrig1 was upregulated in SCLTs, showing that active Rac1 leads to the accumulation of sebocyte precursors in the context of K14ΔNLef1-induced skin tumors. In a search for targets of Rac1, we found cancer progression-related proteins, Dhcr24/Seladin1 and Nuclear protein 1/P8, to be strongly regulated in SCLTs. At last, Rac1 and Dhcr24/Seladin1 were detected in human sebaceous tumors demonstrating a potential high impact of our findings for human skin disease. This is the first study showing that Rac1 activity can lead to malignant progression of skin tumors.

Indexed as

AnimalsBiomarkers, TumorCarcinomaCell DifferentiationCell Line, TumorCell ProliferationDisease ProgressionDNA-Binding ProteinsEpidermisHumansMembrane GlycoproteinsMembrane ProteinsMiceMice, TransgenicNeoplasm ProteinsNerve Tissue ProteinsBiomarkers, TumorDhcr24 protein, mouseDNA-Binding ProteinsLrig1 protein, mouseMembrane GlycoproteinsMembrane ProteinsNeoplasm ProteinsNerve Tissue ProteinsNeuropeptidesNupr1 protein, mouseOxidoreductases Acting on CH-CH Group DonorsPerilipin-2PLIN2 protein, humanPlin2 protein, mouserac1 GTP-Binding ProteinRac1 protein, mouseStearoyl-CoA Desaturase

Identifiers

PMID25659584
OpenAlexW2139499629

What OpenQuestion holds

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Read underepoch 390

Registered trials

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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.