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

Kuo Li Chen, Wun Shaing Wayne Chang, Chun-Hei 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 journalArticle

40 Citations (Scopus)

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 languageEnglish
Pages (from-to)89-98
Number of pages10
JournalCancer Letters
Volume317
Issue number1
DOIs
Publication statusPublished - 2012 Apr 1

Fingerprint

cathepsin S
MAP Kinase Signaling System
Autophagy
Neoplasms
Apoptosis
Cysteine Proteases
Small Interfering RNA
Cell Survival
Cell Death
Phosphorylation

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Chen, Kuo Li ; Chang, Wun Shaing Wayne ; Cheung, Chun-Hei ; Lin, Chun Cheng ; Huang, Chien Chang ; Yang, Yung Ning ; Kuo, Chang Po ; Kuo, Ching Chuan ; Chang, Yi Hsun ; Liu, Ko Jiunn ; Wu, Ching Ming ; Chang, Jang-Yang. / Targeting cathepsin S induces tumor cell autophagy via the EGFR-ERK signaling pathway. In: Cancer Letters. 2012 ; Vol. 317, No. 1. pp. 89-98.
@article{a67a27b01975400fb0d39f0a4fa0babf,
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 Chun-Hei Cheung 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 Jang-Yang Chang",
year = "2012",
month = "4",
day = "1",
doi = "10.1016/j.canlet.2011.11.015",
language = "English",
volume = "317",
pages = "89--98",
journal = "Cancer Letters",
issn = "0304-3835",
publisher = "Elsevier Ireland Ltd",
number = "1",

}

Chen, KL, Chang, WSW, Cheung, C-H, Lin, CC, Huang, CC, Yang, YN, Kuo, CP, Kuo, CC, Chang, YH, Liu, KJ, Wu, CM & Chang, J-Y 2012, 'Targeting cathepsin S induces tumor cell autophagy via the EGFR-ERK signaling pathway', Cancer Letters, vol. 317, no. 1, pp. 89-98. https://doi.org/10.1016/j.canlet.2011.11.015

Targeting cathepsin S induces tumor cell autophagy via the EGFR-ERK signaling pathway. / Chen, Kuo Li; Chang, Wun Shaing Wayne; Cheung, Chun-Hei; Lin, Chun Cheng; Huang, Chien Chang; Yang, Yung Ning; Kuo, Chang Po; Kuo, Ching Chuan; Chang, Yi Hsun; Liu, Ko Jiunn; Wu, Ching Ming; Chang, Jang-Yang.

In: Cancer Letters, Vol. 317, No. 1, 01.04.2012, p. 89-98.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Targeting cathepsin S induces tumor cell autophagy via the EGFR-ERK signaling pathway

AU - Chen, Kuo Li

AU - Chang, Wun Shaing Wayne

AU - Cheung, Chun-Hei

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

PY - 2012/4/1

Y1 - 2012/4/1

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.

UR - http://www.scopus.com/inward/record.url?scp=84856323422&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84856323422&partnerID=8YFLogxK

U2 - 10.1016/j.canlet.2011.11.015

DO - 10.1016/j.canlet.2011.11.015

M3 - Article

VL - 317

SP - 89

EP - 98

JO - Cancer Letters

JF - Cancer Letters

SN - 0304-3835

IS - 1

ER -