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

Kuo Li Chen; Wun Shaing Wayne Chang; Chun Hei Antonio Cheung; Chun Cheng Lin; Chien Chang Huang; Yung Ning Yang; Chang Po Kuo; Ching Chuan Kuo; Yi Hsun Chang; Ko Jiunn Liu; Ching Ming Wu; Jang Yang Chang

doi:10.1016/j.canlet.2011.11.015

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

Kuo Li Chen, Wun Shaing Wayne Chang, Chun Hei Antonio Cheung, Chun Cheng Lin, Chien Chang Huang, Yung Ning Yang, Chang Po Kuo, Ching Chuan Kuo, Yi Hsun Chang, Ko Jiunn Liu, Ching Ming Wu, Jang Yang Chang

Research output: Contribution to journal › Article › peer-review

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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.

Original language	English
Pages (from-to)	89-98
Number of pages	10
Journal	Cancer Letters
Volume	317
Issue number	1
DOIs	https://doi.org/10.1016/j.canlet.2011.11.015
Publication status	Published - 2012 Apr 1

All Science Journal Classification (ASJC) codes

Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.canlet.2011.11.015

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title = "Targeting cathepsin S induces tumor cell autophagy via the EGFR-ERK signaling pathway",

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.",

author = "Chen, {Kuo Li} and Chang, {Wun Shaing Wayne} and Cheung, {Chun Hei Antonio} and Lin, {Chun Cheng} and Huang, {Chien Chang} and Yang, {Yung Ning} and Kuo, {Chang Po} and Kuo, {Ching Chuan} and Chang, {Yi Hsun} and Liu, {Ko Jiunn} and Wu, {Ching Ming} and Chang, {Jang Yang}",

note = "Funding Information: We would like to thank Dr. Noboru Mizushima and Dr. Li-Jin Hsu for their kind supports of the donation of both GFP and GFP-LC3 expression plasmids and Dr. Yi-Rong Chen for his kind donation of the EGFR expression plasmid. The authors declare no conflict of interest. This study was supported by the following grants: 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), and National Health Research Institutes (CA-099-PP-02), Taiwan, ROC.",

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doi = "10.1016/j.canlet.2011.11.015",

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AU - Chen, Kuo Li

AU - Chang, Wun Shaing Wayne

AU - Cheung, Chun Hei Antonio

AU - Lin, Chun Cheng

AU - Huang, Chien Chang

AU - Yang, Yung Ning

AU - Kuo, Chang Po

AU - Kuo, Ching Chuan

AU - Chang, Yi Hsun

AU - Liu, Ko Jiunn

AU - Wu, Ching Ming

AU - Chang, Jang Yang

N1 - Funding Information: We would like to thank Dr. Noboru Mizushima and Dr. Li-Jin Hsu for their kind supports of the donation of both GFP and GFP-LC3 expression plasmids and Dr. Yi-Rong Chen for his kind donation of the EGFR expression plasmid. The authors declare no conflict of interest. This study was supported by the following grants: 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), and National Health Research Institutes (CA-099-PP-02), Taiwan, ROC.

PY - 2012/4/1

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N2 - 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.

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

Abstract

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