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Open Access 01-12-2016 | Research article

Epigenetic silencing of serine protease HTRA1 drives polyploidy

Authors: Nina Schmidt, Inga Irle, Kamilla Ripkens, Vanda Lux, Jasmin Nelles, Christian Johannes, Lee Parry, Kirsty Greenow, Sarah Amir, Mara Campioni, Alfonso Baldi, Chio Oka, Masashi Kawaichi, Alan R. Clarke, Michael Ehrmann

Published in: BMC Cancer | Issue 1/2016

Abstract

Background

Increased 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.

Methods

Mouse 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.

Results

HTRA1 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).

Conclusions

Downregulation 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.

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Title: Epigenetic silencing of serine protease HTRA1 drives polyploidy
Authors: Nina Schmidt
Inga Irle
Kamilla Ripkens
Vanda Lux
Jasmin Nelles
Christian Johannes
Lee Parry
Kirsty Greenow
Sarah Amir
Mara Campioni
Alfonso Baldi
Chio Oka
Masashi Kawaichi
Alan R. Clarke
Michael Ehrmann
Publication date: 01-12-2016
Publisher: BioMed Central
Published in: BMC Cancer / Issue 1/2016
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/s12885-016-2425-8

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