A temporal examination of calcium signaling in cancer- from tumorigenesis, to immune evasion, and metastasis

BACKGROUND: Although the study of calcium (Ca(2+)) is classically associated with excitable cells such as myocytes or neurons, the ubiquity of this essential element in all cellular processes has led to interest in other cell types. The importance of Ca(2+) to apoptosis, cell signaling, and immune activation is of special import in cancer. MAIN: Here we review the current understanding of Ca(2+) in each of these processes vital to the initiation, spread, and drug resistance of malignancies. We describe the involvement of Ca(2+), and Ca(2+) related proteins in cell cycle checkpoints and Ca(2+) dependent apoptosis and discuss their roles in cellular immortalization. The role of Ca(2+) in inter-cellular communication is also discussed in relevance to tumor-stromal communication, angiogenesis, and tumor microinvasion. The role that Ca(2+) plays in immune surveillance and evasion is also addressed. Finally, we discuss the possibility of targeting Ca(2+) singling to address the most pressing topics of cancer treatment: metastatic disease and drug resistance. CONCLUSION: This review discusses the current understanding of Ca(2+) in cancer. By addressing Ca(2+) facilitated angiogenesis, immune evasion, metastasis, and drug resistance, we anticipate future avenues for development of Ca(2+) as a nexus of therapy.