Ca(2+) Signaling Orchestrates Cell Fate Decision in Health and Disease

Cell-fate decisions like cell survival, senescence and apoptosis areregulated by Ca(2+) signals arising from the endoplasmic reticulum,which is in a close proximity to the mitochondria. These organellesare linked by Ca(2+)-transport mechanisms involving the inositol1,4,5-trisphosphate receptor (IP3R). Constitutive IP3 signaling is acommon feature in lymphoma and leukemia that can result in thesurvival, growth and proliferation of cells with oncogenic features.Suppressing the amount of Ca(2+) transferred from the endoplasmicreticulum to the mitochondria increases the resistance to apoptoticstimuli. Interfering with Ca(2+) signaling mechanisms could be exploitedto design therapeutic approach that might achieve selective eliminationof senescent cells by the reactivation of apoptosis. Here in, we provide anoverview of the current knowledge on IP3R-Ca(2+) signaling, how theyaffect cell fate decision and how they can be targeted in the context ofanticancer therapeutical strategy.