Evidence map›Paper›PMID 27388476›Full record

ArticleBMC cancer2016

Epigenetic silencing of serine protease HTRA1 drives polyploidy.

Nina Schmidt, Inga Irle, Kamilla Ripkens, Vanda Lux, Jasmin Nelles, Christian Johannes, Lee Parry, Kirsty Greenow, Sarah Amir, Mara Campioni and 5 more

Open access · goldAbstract read
In one paragraph

Article in BMC cancer, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed, 1 pooled it
2.2field-weighted citation impact, top 12% 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

14 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.

  1. Pooled it
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  4. Review
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  9. Proteases: Pivot Points in Functional Proteomics.Methods in molecular biology (Clifton, N.J.) · 2019
    Review
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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

15 authors at 4 institutions in 4 countries.

Nina SchmidtCentre for Medical Biotechnology, Faculty of Biology and Geography, University Duisburg-Essen, Universitaetsstrasse, D-45117, Essen, Germany.
Inga IrleCentre for Medical Biotechnology, Faculty of Biology and Geography, University Duisburg-Essen, Universitaetsstrasse, D-45117, Essen, Germany.
Kamilla RipkensCentre for Medical Biotechnology, Faculty of Biology and Geography, University Duisburg-Essen, Universitaetsstrasse, D-45117, Essen, Germany.
Vanda LuxCentre for Medical Biotechnology, Faculty of Biology and Geography, University Duisburg-Essen, Universitaetsstrasse, D-45117, Essen, Germany.
Jasmin NellesCentre for Medical Biotechnology, Faculty of Biology and Geography, University Duisburg-Essen, Universitaetsstrasse, D-45117, Essen, Germany.
Christian JohannesCentre for Medical Biotechnology, Faculty of Biology and Geography, University Duisburg-Essen, Universitaetsstrasse, D-45117, Essen, Germany.
Lee ParrySchool of Biosciences, Cardiff University, Cardiff, CF10 3US, UK.
Kirsty GreenowSchool of Biosciences, Cardiff University, Cardiff, CF10 3US, UK.
Sarah AmirSchool of Biosciences, Cardiff University, Cardiff, CF10 3US, UK.
Mara CampioniDepartment of Biochemistry and Biophysics, Section of Pathology, Second University of Naples, 80100, Naples, Italy.
Alfonso BaldiDepartment of Biochemistry and Biophysics, Section of Pathology, Second University of Naples, 80100, Naples, Italy.
Chio OkaDivision of Gene Function in Animals, Nara Institute of Science and Technology, 8916-5 Takayama, Ikoma, Nara, 630-0192, Japan.
Masashi KawaichiDivision of Gene Function in Animals, Nara Institute of Science and Technology, 8916-5 Takayama, Ikoma, Nara, 630-0192, Japan.
Alan R ClarkeSchool of Biosciences, Cardiff University, Cardiff, CF10 3US, UK.
Michael EhrmannCentre for Medical Biotechnology, Faculty of Biology and Geography, University Duisburg-Essen, Universitaetsstrasse, D-45117, Essen, Germany. michael.ehrmann@uni-due.de.
University of Duisburg-Essen · DECardiff University · GBNara Institute of Science and Technology · JPUniversity of Campania "Luigi Vanvitelli" · IT

Funding

Cancer Research UK
6 · The paper itself

Abstract

backgroundIncreased numbers and improperly positioned centrosomes, aneuploidy or polyploidy, and chromosomal instability are frequently observed characteristics of cancer cells. While some aspects of these events and the checkpoint mechanisms are well studied, not all players have yet been identified. As the role of proteases other than the proteasome in tumorigenesis is an insufficiently addressed question, we investigated the epigenetic control of the widely conserved protease HTRA1 and the phenotypes of deregulation.

methodsMouse embryonal fibroblasts and HCT116 and SW480 cells were used to study the mechanism of epigenetic silencing of HTRA1. In addition, using cell biological and genetic methods, the phenotypes of downregulation of HTRA1 expression were investigated.

resultsHTRA1 is epigenetically silenced in HCT116 colon carcinoma cells via the epigenetic adaptor protein MBD2. On the cellular level, HTRA1 depletion causes multiple phenotypes including acceleration of cell growth, centrosome amplification and polyploidy in SW480 colon adenocarcinoma cells as well as in primary mouse embryonic fibroblasts (MEFs).

conclusionsDownregulation of HTRA1 causes a number of phenotypes that are hallmarks of cancer cells suggesting that the methylation state of the HtrA1 promoter may be used as a biomarker for tumour cells or cells at risk of transformation.

Indexed as

DNA MethylationAnimalsCell Line, TumorCell ProliferationCells, CulturedCentrosomeColonic NeoplasmsDNA-Binding ProteinsDown-RegulationEpigenesis, GeneticFibroblastsGene Expression Regulation, NeoplasticHCT116 CellsHigh-Temperature Requirement A Serine Peptidase 1HumansMiceDNA-Binding ProteinsHigh-Temperature Requirement A Serine Peptidase 1HTRA1 protein, humanMBD2 protein, humanSerine EndopeptidasesHTRA1MDB2serine protease

Identifiers

PMID27388476
PMCPMC4936022
OpenAlexW2474865079

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.