Epigenetic silencing of serine protease HTRA1 drives polyploidy. Issue 1 (December 2016)

• Record Type: Journal Article
• Authors: Schmidt, Nina; Irle, Inga; Ripkens, Kamilla; Lux, Vanda; Nelles, Jasmin; Johannes, Christian; Parry, Lee; Greenow, Kirsty; Amir, Sarah; Campioni, Mara; Baldi, Alfonso; Oka, Chio; Kawaichi, Masashi; Clarke, Alan; Ehrmann, Michael
• Is Part Of: BMC cancer. Volume 16:Issue 1(2016)
• Page Start: 1
• Page End: 12
• Publication Date: 2016-12
• Subjects: HTRA1 -- MDB2 -- serine protease; Cancer -- Periodicals; 616.994005
• DOI: 10.1186/s12885-016-2425-8
• Languages: English
• ISSNs: 1471-2407

Abstract

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 ofHTRA1 . 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 theHtrA1 promoter may be used as a biomarker for tumour cells or cells at risk of transformation.