Ion channels and transporters in cancer. 1. Ion channels and cell proliferation in cancer
Ion channels and transporters in cancer. 1. Ion channels and cell proliferation in cancer
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DOI：
10.1152/ajpcell.00047.2011
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发表时间：
2011-08-01
影响因子：
5.5
通讯作者：
Becchetti, Andrea
中科院分区：
文献类型：
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作者：
Becchetti, Andrea
Becchetti A. 癌症中的离子通道和转运蛋白。 1. 癌症中的离子通道和细胞增殖。 Am J Physiol Cell Physiol 301：C255-C265，2011。首次发表于 2011 年 3 月 23 日； doi: 10.1152/ajpcell.00047.2011.-细胞有丝分裂周期的进展需要对内在分子步骤进行精确计时，并与维持细胞处于适当生理环境的环境信号紧密协调。由于其强大的功能灵活性，离子通道协调汇聚在细胞周期机制上的上游和下游信号。电压门控通道和配体门控通道都与正常细胞和肿瘤细胞中不同细胞周期检查点的控制有关。离子通道介导钙信号，该信号破坏有丝分裂过程、循环细胞典型的细胞体积振荡以及自分泌或血管生成因子的胞吐作用。离子通道在增殖中的其他功能仍然存在争议。这些可能取决于也可能不取决于离子运输，因为通道蛋白可以与生长因子和细胞粘附受体形成大分子复合物。与细胞质调节蛋白的直接构象偶联也是可能的。上述过程的紊乱或放松控制可促进肿瘤形成。特定类型的离子通道已被证明参与肿瘤进展的不同阶段，其中通过选择表达更好支持无限制生长的离子通道类型的恶性细胞克隆来增加细胞异质性。然而，离子通道与细胞增殖之间功能关系的全面机制图景尚不可用，部分原因是在活哺乳动物细胞中研究这些过程带来了相当大的实验挑战。毫无疑问，此类研究将成为下一代细胞生理学家最富有成果的研究领域之一。
Becchetti A. Ion channels and transporters in cancer. 1. Ion channels and cell proliferation in cancer. Am J Physiol Cell Physiol 301: C255-C265, 2011. First published March 23, 2011; doi: 10.1152/ajpcell.00047.2011.-Progress through the cell mitotic cycle requires precise timing of the intrinsic molecular steps and tight coordination with the environmental signals that maintain a cell into the proper physiological context. Because of their great functional flexibility, ion channels coordinate the upstream and downstream signals that converge on the cell cycle machinery. Both voltage-and ligand-gated channels have been implicated in the control of different cell cycle checkpoints in normal as well as neoplastic cells. Ion channels mediate the calcium signals that punctuate the mitotic process, the cell volume oscillations typical of cycling cells, and the exocytosis of autocrine or angiogenetic factors. Other functions of ion channels in proliferation are still matter of debate. These may or may not depend on ion transport, as the channel proteins can form macromolecular complexes with growth factor and cell adhesion receptors. Direct conformational coupling with the cytoplasmic regulatory proteins is also possible. Derangement or relaxed control of the above processes can promote neoplasia. Specific types of ion channels have turned out to participate in the different stages of the tumor progression, in which cell heterogeneity is increased by the selection of malignant cell clones expressing the ion channel types that better support unrestrained growth. However, a comprehensive mechanistic picture of the functional relations between ion channels and cell proliferation is yet not available, partly because of the considerable experimental challenges offered by studying these processes in living mammalian cells. No doubt, such studies will constitute one of the most fruitful research fields for the next generation of cell physiologists.