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

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

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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    Chen, K. L., Chang, W. S. W., Cheung, C. H. A., Lin, C. C., Huang, C. C., Yang, Y. N., Kuo, C. P., Kuo, C. C., Chang, Y. H., Liu, K. J., Wu, C. M., & Chang, J. Y. (2012). Targeting cathepsin S induces tumor cell autophagy via the EGFR-ERK signaling pathway. Cancer Letters, 317(1), 89-98. https://doi.org/10.1016/j.canlet.2011.11.015