Cancer Progression and the Calcium Signaling Toolkit: Expanding Dimensions and Perspectives

Calcium signaling is a key controller of numerous cellular events and is intricately linked to many processes that are critical pathways in cancer progression. This review revisits the calcium signaling toolkit in cancer, with a focus on calcium regulation of processes that go beyond the originally defined "classic" hallmarks of cancer such as those associated with proliferation, metastasis, and resistance to cell death pathways. We will consider calcium signaling in the context of the more recently proposed hallmarks of cancer, emerging hallmarks, and cancer-enabling characteristics. This broader examination of calcium signaling and its toolkit members will encompass processes such as metabolic reprogramming, evasion of immune destruction, cellular phenotypic plasticity, senescence, genome instability, and nonmutational epigenetic reprogramming. These cancer features and their interactions with calcium signaling will frequently be analyzed through the lenses of therapy resistance and the complexities of the tumor microenvironment.