期刊
CANCER LETTERS
卷 317, 期 1, 页码 89-98出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2011.11.015
关键词
EGFR; Cathepsin S; Autophagy; Apoptosis; ERK
类别
资金
- National Science Council [NSC99-2323-B-400-006, NSC99-2323-B-400-007, NSC99-2120-M-006-005, NSC 99-2323-B-007-001]
- Department of Health [DOH99-TD-C-111-004]
- National Health Research Institutes, Taiwan, ROC [CA-099-PP-02]
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. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
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