GSK-3 is a multifunctional kinase that is located in the cytosol, nucleus, and mitochondria of all cell types, and it is involved in the pathogenesis of a variety of diseases. In cancer, GSK-3 modulates the response of the cell death machinery to stress stimuli, including chemotherapeutics. Mitochondria are at the heart of the integration between survival and noxious signals; therefore, modulation of the mitochondrial functions carried out by GSK-3 is profoundly involved in the apoptosis escape capabilities that hallmark neoplasms. This review briefly covers the mechanistic interactions among oncogenic kinase pathways, GSK-3 activity and subsequent modulation of mitochondrial functions that shape the pro-survival phenotype of cancer cells, such as control of redox homeostasis and inhibition of the mitochondrial permeability transition pore.
Keywords: GSK-3; PTP; ROS; apoptosis; cancer; chemotherapeutics; mitochondria.