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Please use this identifier to cite or link to this item:
http://ir.nhri.org.tw/handle/3990099045/9903
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Title: | Targeting cathepsin S induces tumor cell autophagy via the EGFR-ERK signaling pathway |
Authors: | Chen, KL;Chang, WSW;Lin, CC;Cheung, CHA;Kuo, CP;Kuo, CC;Chang, YH;Liu, KJ;Chang, JY |
Contributors: | National Institute of Cancer Research |
Abstract: | Cathepsin S is a vital cellular cysteine protease that is frequently amplified and over-expressed in various human cancers. In this study, we report that targeting cathpesin S could induce tumor cell autophagy via the EGFR-ERK signaling pathway. Cancer cells treated with cathepsin S inhibitors [α-ketoamide inhibitor (6r), Z-FL-COCHO (ZFL)] and cathepsin S-specific siRNA induced autophagy as indicated by an increase in the cleavage of the microtubule-associated protein light chain 3B (LC3B) and the formation of membrane-bound autophagic vacuoles (AVOs). In addition, co-treatment of a specific inhibitor of autophagy, 3-methyladenine (3MA), inhibited the 6r-induced autophagy in cancer cells. Further Western blot analysis revealed that targeting cathepsin S induced cancer cell autophagy through the activation of EGF receptor and its downstream MAPK-related signaling pathways. The induction of autophagy by targeting cathepsin S subsequently leads to the activation of apoptosis as indicated by both the up-regulation of caspase-9/3 activity, the down-regulation of Bcl-2, Bcl-XL and the altered mitochondrial membrane retention potential in cells. The application of the autophagy inhibitor, 3MA, was able to inhibit the process of apoptosis induced by the cathepsin S inhibitor 6r in cancer cells. In conclusion, the current study reveals that cathepsin S inhibitor is able to induce cancer cell autophagy through the EGF receptor signaling pathways, which may provide therapeutic benefit in cancer patients who are less sensitive to apoptosis-inducing agents. |
Date: | 2011-04 |
Relation: | Cancer Research. 2011 Apr;71(Suppl. 8):Meeting Abstract 2864. |
Link to: | http://dx.doi.org/10.1158/1538-7445.am2011-2864 |
JIF/Ranking 2023: | http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0008-5472&DestApp=IC2JCR |
Cited Times(WOS): | https://www.webofscience.com/wos/woscc/full-record/WOS:000209701400111 |
Appears in Collections: | [張俊彥] 會議論文/會議摘要 [劉柯俊] 會議論文/會議摘要 [張文祥] 會議論文/會議摘要 [郭靜娟] 會議論文/會議摘要
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