In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 71, No. 8_Supplement ( 2011-04-15), p. 2864-2864
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. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2864. doi:10.1158/1538-7445.AM2011-2864
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2011-2864
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2011
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
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