Various Aspects of Calcium Signaling in the Regulation of Apoptosis, Autophagy, Cell Proliferation, and Cancer

Calcium (Ca(2+)) is a major second messenger in cells and is essential for the fate and survival of all higher organisms. Different Ca(2+) channels, pumps, or exchangers regulate variations in the duration and levels of intracellular Ca(2+), which may be transient or sustained. These changes are then decoded by an elaborate toolkit of Ca(2+)-sensors, which translate Ca(2+) signal to intracellular operational cell machinery, thereby regulating numerous Ca(2+)-dependent physiological processes. Alterations to Ca(2+) homoeostasis and signaling are often deleterious and are associated with certain pathological states, including cancer. Altered Ca(2+) transmission has been implicated in a variety of processes fundamental for the uncontrolled proliferation and invasiveness of tumor cells and other processes important for cancer progression, such as the development of resistance to cancer therapies. Here, we review what is known about Ca(2+) signaling and how this fundamental second messenger regulates life and death decisions in the context of cancer, with particular attention directed to cell proliferation, apoptosis, and autophagy. We also explore the intersections of Ca(2+) and the therapeutic targeting of cancer cells, summarizing the therapeutic opportunities for Ca(2+) signal modulators to improve the effectiveness of current anticancer therapies.