The intersection between cysteine proteases, Ca²⁺ signalling and cancer cell apoptosis

Apoptosis is a highly complex and regulated cell death pathway that safeguards the physiological balance between life and death. Over the past decade, the role of Ca²⁺ signalling in apoptosis and the mechanisms involved have become clearer. The initiation and execution of apoptosis is coordinated by three distinct groups of cysteines proteases: the caspase, calpain and cathepsin families. Beyond its physiological importance, the ability to evade apoptosis is a prominent hallmark of cancer cells. In this review, we will explore the involvement of Ca²⁺ in the regulation of caspase, calpain and cathepsin activity, and how the actions of these cysteine proteases alter intracellular Ca²⁺ handling during apoptosis. We will also explore how apoptosis resistance can be achieved in cancer cells through deregulation of cysteine proteases and remodelling of the Ca²⁺ signalling toolkit.