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Volume-Sensitive Organic Osmolyte/Anion Channels in Cancer: Novel Approaches to Studying Channel Modulation Employing Proteomics Technologies
Department of Pharmacology, School of Medical Sciences, University of Bristol, Bristol BS8 1TD. UK
Address for correspondence: Roland Z. Kozlowski, Department of Pharmacology, School of Medical Sciences, University of Bristol, University Walk, Bristol BS8 1TD. UK. Voice: 44-117-954-6875; fax: 44-117-925-2659. Roland.Kozlowski{at}bristol.ac.uk aThese authors contributed equally to this work.
Key elements of tumor development include proliferation, migration, invasiveness, and angiogenesis. Activation of the volume-sensitive organic osmolyte/anion channel (VSOAC) has been suggested to play a role in all of these processes. VSOACs may therefore represent an important therapeutic target in the etiology of cancer. However, pharmacological inhibitors of VSOAC are nonselective and of low potency, highlighting the importance of identifying novel regulators of the channel. The use of electrophysiological methods coupled with techniques such as pull-down assays, yeast 2-hybrid, and functional protein arrays have already proved valuable in studying protein-protein interactions in a variety of systems. Some of these methods have been used to identify small molecules that modulate the function of other types of ion channels. Given that several proteins have already been identified as putative modulators of VSOACs, proteomics technologies may prove useful in elucidating the molecular identity of VSOACs and helpful in identifying novel modulators of channel function. In this paper, we review the involvement of VSOACs in tumor development processes and its regulation by pharmacological agents and cellular proteins. Proteomic approaches to study protein-protein interactions and how such approaches may be used to study VSOACs are also discussed. We speculate on how modulation of protein-protein interactions may result in the identification of a novel class of compounds for modulating VSOACs.
Key Words: proteomics • protein-protein interactions • volume-sensitive organic osmolyte/anion channel • VSOAC • cancer
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