Article

Targeting cathepsin S induces tumor cell autophagy via the EGFR-ERK signaling pathway.

National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan, ROC.
Cancer letters (impact factor: 4.86). 11/2011; 317(1):89-98. DOI:10.1016/j.canlet.2011.11.015 pp.89-98
Source: PubMed

ABSTRACT Cathepsin S is a cellular cysteine protease, which is frequently over-expressed in human cancer cells and plays important role in tumor metastasis. However, the role of cathepsin S in regulating cancer cell survival and death remains undefined. The aim of this study was to determine whether targeting cathepsin S could induce autophagy/apoptosis in cancer cells. In this study, we demonstrated that targeting cathepsin S by either specific small molecular inhibitors or cathepsin S siRNA induced autophagy and subsequent apoptosis in human cancer cells, and the induction of autophagy was dependent on the phosphorylation of EGFR and activation of the EGFR-related ERK/MAPK-signaling pathway. In conclusion, the current study reveals that cathepsin S plays an important role in the regulation of cell autophagy through interference with the EGFR-ERK/MAPK-signaling pathway.

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Keywords

cancer cells
 
cathepsin S
 
cathepsin S siRNA induced autophagy
 
cell autophagy
 
cellular cysteine protease
 
EGFR-ERK/MAPK-signaling pathway
 
EGFR-related ERK/MAPK-signaling pathway
 
human cancer cells
 
over-expressed
 
phosphorylation
 
regulating cancer cell survival
 
specific small molecular inhibitors
 
subsequent apoptosis
 
targeting cathepsin S
 
tumor metastasis