Journal
CANCER LETTERS
Volume 293, Issue 1, Pages 15-22Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2009.12.002
Keywords
Proteasome inhibitor; Cancer; Signaling; Autophagy; Proliferation
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Funding
- National Basic Research Program of China [2010CB529305]
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The ubiquitin-proteasome system is a major pathway for protein degradation. Targeting this pathway using proteasome inhibitors represents a novel approach for the treatment of cancer. Proteasome inhibitors lower cell proliferation and induce apoptosis in solid and hematologic malignancies through multiple mechanisms, including stabilization of cell cycle regulators and pro-apoptotic factors, stimulation of bone morphogenetic protein signaling, inhibition of protein translation, and sensitization to ligand-induced apoptosis. In this connection, proteasome inhibition activates macroautophagy, a compensatory protein degradation system, as well as other pro-survival signaling pathways. Inhibition of these auto-protective responses sensitizes cancer cells to the anti-proliferative effects of proteasome inhibitors. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
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