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Calcium-mediated signal transduction: biology, biochemistry, and therapy

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Abstract

The process of proliferation, invasion and metastasis is a complex one which involves both the autonomy of the malignant cells and their interaction with the cellular and extracellular environments. The way in which the tumor cells respond to cellular and extracellular stimuli is regulated through transduction of those signals and translation into cellular activity. Transmembrane signal transduction involves three major categories of events: ion channel activation, transmission through guanine nucleotide binding protein intermediates with production of second messengers, and phosphorylation events. A frequent common denominator of these different pathways is a cellular calcium homeostasis. Calcium may be both a result of and a regulator of many of these signal transduction pathways and has been shown to have a role in the regulation of proliferation, invasion, and metastatic potential. The understanding and application of the basic tenets of these pathways to tumor cell proliferation, invasion, and metastases opens a new target for therapeutic intervention. We have identified a novel agent, CAI, which through inhibition of stimulated calcium influx inhibits proliferation and migrationin vitro, and growth and dissemination in human cancer xenograftsin vivo. CAI offers a new approach to cancer therapy, signal transduction therapy.

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Abbreviations

G protein:

Guanine nucleotide binding protein

CAI:

Carboxyamido-triazole

EGF:

Epidermal Growth Factor

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  1. Laboratory of Pathology, Signal Transduction and Prevention Unit, National Cancer Institute, Building 10, Room 2A33, 9000 Rockville Pike, 20892, Bethesda, ML, USA

    Kristina Cole & Elise Kohn

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  1. Kristina Cole
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Cole, K., Kohn, E. Calcium-mediated signal transduction: biology, biochemistry, and therapy. Cancer Metast Rev 13, 31–44 (1994). https://doi.org/10.1007/BF00690417

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