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Cancer Res. 2010 Nov 15;70(22):8988-93. doi: 10.1158/0008-5472.CAN-10-2225. Epub 2010 Oct 26.

Heat shock protein 60 regulation of the mitochondrial permeability transition pore in tumor cells.

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Prostate Cancer Discovery and Development Program, The Wistar Institute Cancer Center, Philadelphia, Pennsylvania 19104, USA.


Mitochondrial apoptosis plays a critical role in tumor maintenance and dictates the response to therapy in vivo; however, the regulators of this process are still largely elusive. Here, we show that the molecular chaperone heat shock protein 60 (Hsp60) directly associates with cyclophilin D (CypD), a component of the mitochondrial permeability transition pore. This interaction occurs in a multichaperone complex comprising Hsp60, Hsp90, and tumor necrosis factor receptor-associated protein-1, selectively assembled in tumor but not in normal mitochondria. Genetic targeting of Hsp60 by siRNA triggers CypD-dependent mitochondrial permeability transition, caspase-dependent apoptosis, and suppression of intracranial glioblastoma growth in vivo. Therefore, Hsp60 is a novel regulator of mitochondrial permeability transition, contributing to a cytoprotective chaperone network that antagonizes CypD-dependent cell death in tumors.

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