Sensitivity of GBM cells to cAMP agonist-mediated apoptosis correlates with CD44 expression and agonist resistance with MAPK signaling
Paul M Daniel, Gulay Filiz, Theo Mantamadiotis
CELL DEATH & DISEASE | NATURE PUBLISHING GROUP | Published : 2016
In some cell types, activation of the second messenger cAMP leads to increased expression of proapoptotic Bim and subsequent cell death. We demonstrate that suppression of the cAMP pathway is a common event across many cancers and that pharmacological activation of cAMP in glioblastoma (GBM) cells leads to enhanced BIM expression and apoptosis in specific GBM cell types. We identified the MAPK signaling axis as the determinant of cAMP agonist sensitivity in GBM cells, with high MAPK activity corresponding to cAMP resistance and low activity corresponding to sensitization to cAMP-induced apoptosis. Sensitive cells were efficiently killed by cAMP agonists alone, while targeting both the cAMP a..View full abstract
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Awarded by CASS Foundation Medical Research Grant
This work was supported by the Department of Pathology, University of Melbourne and a CASS Foundation Medical Research Grant (6236). We thank members of the Department of Pathology and School of Biomedical Sciences at The University of Melbourne for their support.