Monzani Elena, Shtil Alexander A, La Porta Caterina A M
Department of Biomolecular Science and Biotechnology, University of Milan, Milan, Italy.
Curr Drug Targets. 2007 Oct;8(10):1132-7. doi: 10.2174/138945007782151342.
Cell viability and motility are critical for cancer progression. Among a plethora of mechanisms that regulate these phenotypes, the balance of water and monovalent metal cations plays a pivotal role in the dynamics of focal contacts and cytoskeletal rearrangements at the cell's leading edge. Furthermore, cell survival requires the optimal concentration of water and solutes. This balance is largely maintained by aquaporins (AQPs), a family of 13 small integral plasma membrane proteins whose major function is the transport of water and small solutes across the plasma membrane. We review the recent knowledge about the role of AQPs in cell migration, survival, tumor angiogenesis and metastasis with the focus on therapeutic possibilities to prevent these clinically unfavourable events. The review discusses the inhibition of AQP expression and/or AQP-mediated water influx by acetazolamide, cyclophosphamide, topiramate, thiopental, phenobarbital and propofol. Down-regulation of water transport by these drugs affects cancer cell migration and metastasis. We conclude that AQPs can be considered a point where the mechanisms of survival and motility converge. Therapeutic targeting of AQPs may thus be advantageous for blocking the mechanism common for a number of key cancer phenotypes.
细胞活力和运动能力对癌症进展至关重要。在众多调节这些表型的机制中，水和单价金属阳离子的平衡在细胞前沿焦点接触和细胞骨架重排的动态过程中起着关键作用。此外，细胞存活需要水和溶质的最佳浓度。这种平衡很大程度上由水通道蛋白（AQP）维持，水通道蛋白是一个由13种小的整合质膜蛋白组成的家族，其主要功能是跨质膜运输水和小溶质。我们综述了关于水通道蛋白在细胞迁移、存活、肿瘤血管生成和转移中作用的最新知识，重点关注预防这些临床不良事件的治疗可能性。该综述讨论了乙酰唑胺、环磷酰胺、托吡酯、硫喷妥钠、苯巴比妥和丙泊酚对水通道蛋白表达和/或水通道蛋白介导水内流的抑制作用。这些药物对水运输的下调影响癌细胞的迁移和转移。我们得出结论，水通道蛋白可被视为存活和运动机制的交汇点。因此，对水通道蛋白进行治疗性靶向可能有利于阻断多种关键癌症表型共有的机制。
