Chapter 17

Potentiality and Limitations of a Strategy for the Control of Cell Proliferation: The Block of Ca2+ Entry

Luca Munaron, Susanna Antoniotti, Alessandra Fiorio Pla and Davide Lovisolo

Abstract

<p>Ca2+ signalling is involved in virtually all cellular processes: among the others, it controls cell survival, proliferation and death regulating a plethora of intracellular enzymes located in the cytoplasm, nucleus and organelles.</p> <p>Changes in the cytosolic free Ca2+ concentration may be due either to release from the intracellular Ca2+ stores or to influx from the extracellular medium, through the opening of plasmamembrane calcium-permeable channels. In particular, Ca2+ entry from the extracellular space is a mechanism able to sustain long lasting intracellular Ca2+ elevations: this signal, activated by many growth factors and mitogens in normal and tumoral tissues, is linked to DNA transcription and duplication, finally leading to cell proliferation.</p> <p>In the last years many informations have been provided about the transduction mechanisms related to Ca2+ entry induced by mitogenic factors, mostly binding to tyrosine kinase receptors, but also to G-protein coupled ones. Nevertheless, some key points remain to be fully clarified: among them, the molecular structure of the Ca2+ channels involved, their regulation by intracellular messengers, and the modes through which specificity is achieved.</p> <p>The increasing knowledge on Ca2+ entry-dependent control of proliferation may provide a more satisfactory understanding of pathological alterations, including cancer progression and angiogenesis. A detailed description of the mechanisms that trigger Ca2+ entry, and in particular the definition of calcium-permeable channels and their modulators at the molecular levels, will greatly improve our possibility to take advantage of Ca2+ entry regulation as a therapeutic approach for the control of cell proliferation, designing antibodies or molecules with low side effects and specific channel blocker functions. The review will focuse on this topic.</p>

Total Pages: 417-433 (17)

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