Ion channels: functional expression and therapeutic potential in cancer. Colloquium on Ion Channels and Cancer
Journal Title: EMBO Reports - Year 2008, Vol 9, Issue 6
Abstract
It is becoming increasingly clear that TRP channels are involved in cancer progression (Bödding, 2007; Prevarskaya et al, 2007). In relation to prostate cancer, N. Prevarskaya (Villeneuve d'Ascq, France) described the role of classic TRP channels (TRPC), vanilloid TRP channels (TRPV) and melastatin TRP channels (TRPM) in the development of androgen independence. Among other things, androgen independence leads to apoptosis resistance, making the tumour difficult to treat clinically. Prevarskaya's group showed that Ca2+ entry on activation of different TRP channels could either stimulate proliferation through TRPC6 and TRPV6, or induce apoptosis through TRPC1/TRPC4 and TRPM8. Interestingly, the expression and subcellular distribution of TRPM8 is regulated by androgens, and is dependent on metastatic potential. Therefore, TRPM8 could lead to Ca2+ entry through the plasma membrane or Ca2+ release from intracellular stores, and this could contribute to the development of androgen independence (Bidaux et al, 2007). D. Bates (Bristol, UK) described the role of TRP channels in vascular permeability and angiogenesis. Both TRPC3 and TRPC6 channels are expressed in rodent microvasculature in which activation by VEGF or diacyl-glycerol leads to increased intracellular Ca2+ and vascular permeability. A dominant negative TRPC6 construct expressed in human microvascular endothelial cells abolished both the increased intracellular Ca2+ response to VEGF and cell migration. Such a role implies TRP involvement in the cancer process as angiogenesis is an important aspect of tumour growth and metastasis formation.
Authors and Affiliations
Scott P. Fraser, Luis A. Pardo
Keywords
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- EP ID EP679938
- DOI 10.1038/embor.2008.75
- Views 35
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