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Epigenetic silencing of serine protease HTRA1 drives polyploidy

Nina Schmidt1, Inga Irle1, Kamilla Ripkens1

  • 1Centre for Medical Biotechnology, Faculty of Biology and Geography, University Duisburg-Essen, Universitaetsstrasse, D-45117, Essen, Germany.

BMC Cancer
|July 9, 2016
PubMed
Abstract

Insights

The protease HTRA1 is epigenetically silenced in cancer cells by MBD2. Its downregulation accelerates cell growth and causes centrosome amplification and polyploidy, hallmarks of cancer.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Epigenetics

Background:

  • Cancer cells exhibit increased centrosomes, aneuploidy, polyploidy, and chromosomal instability.
  • Checkpoint mechanisms are partially understood, but not all contributing factors are identified.
  • The role of proteases beyond the proteasome in tumorigenesis requires further investigation.

Purpose of the Study:

  • To investigate the epigenetic control of the protease HTRA1.
  • To examine the cellular phenotypes associated with HTRA1 deregulation.

Main Methods:

  • Studied epigenetic silencing of HTRA1 in mouse embryonal fibroblasts and HCT116 and SW480 cells.
  • Employed cell biological and genetic methods to investigate HTRA1 downregulation phenotypes.

Main Results:

  • HTRA1 is epigenetically silenced in HCT116 colon carcinoma cells through the MBD2 protein.
  • HTRA1 depletion leads to accelerated cell growth, centrosome amplification, and polyploidy in SW480 cells and primary mouse embryonic fibroblasts (MEFs).

Conclusions:

  • HTRA1 downregulation induces phenotypes characteristic of cancer cells.
  • The methylation status of the HtrA1 promoter could serve as a biomarker for tumor cells or those at risk of transformation.
Keywords:
HTRA1MDB2serine protease

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