Activation of mitochondrial ERK protects cancer cells from death through inhibition of the permeability transition

• DOI: 10.1073/pnas.0912742107
• Publication Date: 2009-12-23T02:09:29Z
• Authors: Andrea Rasola; Marco Sciacovelli; Federica Chiara; Boris Pantic; William S. Brusilow; Paolo Bernardi
• Keywords: DU145

We studied human cancer cell models in which we detected constitutive activation of ERK. A fraction active ERK was found to be located mitochondria RWPE-2 cells, obtained by v-Ki-Ras transformation the epithelial prostate RWPE-1 line; metastatic DU145 cells; and osteosarcoma SAOS-2 cells. All these tumor cells displayed marked resistance death caused apoptotic stimuli like arachidonic acid BH3 mimetic EM20-25, cause through mitochondrial permeability transition pore (PTP). PTP desensitization ensuing induced or EM20-25 could ablated inhibiting with drug PD98059 a selective inhibitor peptide. inhibition enhanced glycogen synthase kinase-3 (GSK-3)-dependent phosphorylation regulator cyclophilin D, whereas GSK-3 protected from opening. Neither nor observed non-transformed Thus, desensitizes signaling axis that involves finding provides mechanistic basis for increased apoptosis neoplastic