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.
authors.affiliation: National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan, ROC.
authors.forename: Kuo-Li
authors.initials: KL
authors.lastname: Chen
authors.forename: Wun-Shaing Wayne
authors.initials: WS
authors.lastname: Chang
authors.forename: Chun Hei Antonio
authors.initials: CH
authors.lastname: Cheung
authors.forename: Chun-Cheng
authors.initials: CC
authors.lastname: Lin
authors.forename: Chien-Chang
authors.initials: CC
authors.lastname: Huang
authors.forename: Yung-Ning
authors.initials: YN
authors.lastname: Yang
authors.forename: Chang-Po
authors.initials: CP
authors.lastname: Kuo
authors.forename: Ching-Chuan
authors.initials: CC
authors.lastname: Kuo
authors.forename: Yi-Hsun
authors.initials: YH
authors.lastname: Chang
authors.forename: Ko-Jiunn
authors.initials: KJ
authors.lastname: Liu
authors.forename: Ching-Ming
authors.initials: CM
authors.lastname: Wu
authors.forename: Jang-Yang
authors.initials: JY
authors.lastname: Chang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001343:Autophagy / Q000187:drug effects*; D016466:CHO Cells; D002403:Cathepsins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D066246:ErbB Receptors / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D019073:HT29 Cells; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D034622:RNA Interference; D015398:Signal Transduction / Q000187:drug effects*; D013997:Time Factors; D014162:Transfection
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; C512478:EGFR protein, human; D066246:ErbB Receptors; D048049:Extracellular Signal-Regulated MAP Kinases; D002403:Cathepsins; C028217:cathepsin S