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Review
. 2018 Apr 3:8:25.
doi: 10.1186/s13578-018-0223-5. eCollection 2018.

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

MengMeng Xu #  1   2 , Andreas Seas #  1 , Musa Kiyani #  3   4 , Keven S Y Ji #  3 , Hannah N Bell #  1
Affiliations
Review

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

MengMeng Xu et al. Cell Biosci. .

Abstract

Background: Although the study of calcium (Ca2+) 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 Ca2+ to apoptosis, cell signaling, and immune activation is of special import in cancer.

Main: Here we review the current understanding of Ca2+ in each of these processes vital to the initiation, spread, and drug resistance of malignancies. We describe the involvement of Ca2+, and Ca2+ related proteins in cell cycle checkpoints and Ca2+ dependent apoptosis and discuss their roles in cellular immortalization. The role of Ca2+ in inter-cellular communication is also discussed in relevance to tumor-stromal communication, angiogenesis, and tumor microinvasion. The role that Ca2+ plays in immune surveillance and evasion is also addressed. Finally, we discuss the possibility of targeting Ca2+ singling to address the most pressing topics of cancer treatment: metastatic disease and drug resistance.

Conclusion: This review discusses the current understanding of Ca2+ in cancer. By addressing Ca2+ facilitated angiogenesis, immune evasion, metastasis, and drug resistance, we anticipate future avenues for development of Ca2+ as a nexus of therapy.

Keywords: Calcium signaling; Cancer; Drug resistance; Immortalization; Metastasis; Tumor-stromal interaction.

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Figures

Fig. 1
Fig. 1
Ca2+ and associated protein involvement in cellular proliferation. The affect of Ca2+ concentration on key cellular proteins are diagrammed
Fig. 2
Fig. 2
Schematic of cell cycle, and the influence of calcium in G1/S transitioning via the MAPK pathway. Note that Ras, a protein under control of cytosolic calcium levels, also regulates the G0/G1 transition, and is important throughout G1 phase
Fig. 3
Fig. 3
Ca2+ signaling in tumor progression. The involvement of Ca2+ in every step of tumor development, metastasis, and current knowledge on Ca2+ facilitated drug resistance
See this image and copyright information in PMC

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References

    1. Carafoli E. Calcium signaling: a tale for all seasons. Proc Natl Acad Sci USA. 2002;99:1115–1122. doi: 10.1073/pnas.032427999. - DOI - PMC - PubMed
    1. Berridge MJ, Lipp P, Bootman MD. The versatility and universality of calcium signalling. Nat Rev Mol Cell Biol. 2000;1:11–21. doi: 10.1038/35036035. - DOI - PubMed
    1. Zhivotovsky B, Orrenius S. Calcium and cell death mechanisms: a perspective from the cell death community. Cell Calcium. 2011;50:211–221. doi: 10.1016/j.ceca.2011.03.003. - DOI - PubMed
    1. Wei C, Wang X, Chen M, Ouyang K, Song LS, Cheng H. Calcium flickers steer cell migration. Nature. 2009;457:901–905. doi: 10.1038/nature07577. - DOI - PMC - PubMed
    1. Di Benedetto G, Scalzotto E, Mongillo M, Pozzan T. Mitochondrial Ca(2)(+) uptake induces cyclic AMP generation in the matrix and modulates organelle ATP levels. Cell Metab. 2013;17:965–975. doi: 10.1016/j.cmet.2013.05.003. - DOI - PubMed

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