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Cellular senescence induced by cathepsin X downregulation.
MedLine Citation:
PMID:  21616554     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Cellular senescence represents a powerful tumor suppressor mechanism to prevent proliferation and invasion of malignant cells. Since tumor cells as well as primary fibroblasts lacking the lysosomal cysteine-type carboxypeptidase cathepsin X exhibit a reduced invasive capacity, we hypothesized that the underlying reason may be the induction of cellular senescence. To investigate the cellular and molecular mechanisms leading to diminished migration/invasion of cathepsin X-deficient cells, we have analyzed murine embryonic fibroblasts (MEF) derived from cathepsin X-deficient mice and neonatal human dermal fibroblasts (NHDF) transfected with siRNAs targeting cathepsin X. Remarkably, both cell types exhibited a flattened and enlarged cell body, a characteristic phenotype of senescent cells. Additional evidence for accelerated senescence was obtained by detection of the common senescence marker β-galactosidase. Further examination revealed increased expression levels of senescence-associated genes such as p16, p21, p53, and caveolin in these cells along with a reduced proliferation rate. The accelerated cellular senescence induced by cathepsin X deficiency was rescued by simultaneous expression of exogenous cathepsin X. Finally, cell cycle analysis confirmed a marked reduction of the synthesis rate and prolongation of the S-phase, while susceptibility to apoptosis of cathepsin X-deficient cells remained unchanged. In conclusion, cathepsin X deficiency leads to accelerated cellular senescence and consequently to diminished cellular proliferation and migration/invasion implying a potential role of cathepsin X in bypassing cellular senescence.
Authors:
Steffen Kraus; Thea Bunsen; Simon Schuster; Monika A Cichoń; Marlene Tacke; Thomas Reinheckel; Christian P Sommerhoff; Marianne Jochum; Dorit K Nägler
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-5-24
Journal Detail:
Title:  European journal of cell biology     Volume:  -     ISSN:  1618-1298     ISO Abbreviation:  -     Publication Date:  2011 May 
Date Detail:
Created Date:  2011-5-27     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7906240     Medline TA:  Eur J Cell Biol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011 Elsevier GmbH. All rights reserved.
Affiliation:
Division of Clinical Chemistry and Clinical Biochemistry, University Hospital of Surgery, Ludwig-Maximilians-University, Nussbaumstr. 20, 80336 Munich, Germany.
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