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- Title
Up-regulation of cathepsin B expression and enhanced secretion in mitochondrial DNA-depleted osteosarcoma cells.
- Authors
Isabelle Hamer; Edouard Delaive; Marc Dieu; Fadi Abdel-sater; Ludovic Mercy; Michel Jadot; Thierry Arnould
- Abstract
Background information. mtDNA (mitochondrial DNA) mutations that impair oxidative phosphorylation can contribute to carcinogenesis through the increased production of reactive oxygen species and through the release of proteins involved in cell motility and invasion. On the other hand, many human cancers are associated with both the up-regulation and the increased secretion of several proteases and heparanase. In the present study, we tried to determine whether the depletion in mtDNA could modulate the expression and/or the secretion of some lysosomal hydrolases in the 143B osteosarcoma cells, as these mtDNA-depleted cells are characterized by a higher degree of invasiveness than the parental cells.Results. In comparison with the parental cells, we measured a higher amount of procathepsin B in the conditioned culture medium of the 143B cells lacking mtDNA (ρ0143B cells), as well as a rise in the specific activity of intracellular cathepsin B. In addition, we observed an activation of the transcription factor NF-κB (nuclear factor κB) in the cells devoid of functional mitochondria. Finally, we demonstrated that the down-regulation of the NF-κB p65 subunit by RNA interference led to a reduction in cathepsin B expression in ρ0143B cells.Conclusions. The up-regulation of cathepsin B by NF-κB, followed by its secretion into the extracellular environment, might be partly responsible for the previously reported invasiveness of the mtDNA-depleted 143B osteosarcoma cells.
- Subjects
GENETIC regulation; MITOCHONDRIAL DNA; OSTEOSARCOMA; GENETIC mutation; PHOSPHORYLATION; CARCINOGENESIS; REACTIVE oxygen species; NF-kappa B
- Publication
Biology of the Cell (Wiley-Blackwell), 2009, Vol 101, Issue 1, p31
- ISSN
0248-4900
- Publication type
Article
- DOI
10.1042/BC20080043