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

被引：67

作者：

Chen, Kuo-Li ^{[1
]}

Chang, Wun-Shaing Wayne ^{[1
]}

Cheung, Chun Hei Antonio ^{[2
]}

Lin, Chun-Cheng ^{[3
]}

Huang, Chien-Chang ^{[1
]}

Yang, Yung-Ning ^{[1
,4
]}

Kuo, Chang-Po ^{[5
]}

Kuo, Ching-Chuan ^{[1
]}

Chang, Yi-Hsun ^{[1
]}

Liu, Ko-Jiunn ^{[1
]}

Wu, Ching-Ming ^{[6
]}

Chang, Jang-Yang ^{[1
,7
]}

机构：

[1] Natl Hlth Res Inst, Natl Inst Canc Res, Tainan 70456, Taiwan

[2] Natl Cheng Kung Univ, Coll Med, Dept Pharmacol, Tainan 70101, Taiwan

[3] Natl Tsing Hua Univ, Dept Chem, Hsinchu, Taiwan

[4] Natl Def Med Ctr, Grad Inst Life Sci, Taipei, Taiwan

[5] Triserv Gen Hosp, Dept Anesthesiol, Taipei, Taiwan

[6] Natl Cheng Kung Univ, Coll Med, Dept Cell Biol & Anat, Tainan 70101, Taiwan

[7] Natl Cheng Kung Univ Hosp, Div Hematol & Oncol, Dept Internal Med, Tainan 70428, Taiwan

来源：

CANCER LETTERS | 2012年 / 317卷 / 01期

关键词：

EGFR; Cathepsin S; Autophagy; Apoptosis; ERK; MEDIATED AUTOPHAGY; UP-REGULATION; DEATH; EXPRESSION; APOPTOSIS; INHIBITION; SURVIVAL; INVASION; GROWTH;

D O I：

10.1016/j.canlet.2011.11.015

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

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.

引用

页码：89 / 98

页数：10

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