文章：

钙在肿瘤转移中的作用：已知的新角色

Calcium in tumour metastasis: new roles for known actors

原文发布日期：2011-06-09

DOI: 10.1038/nrc3105

类型: Review Article

开放获取: 否

要点：

1. The ubiquitous second messenger Ca²⁺ is a crucial regulator of cell migration. Although increases in intracellular Ca²⁺ concentration ([Ca²⁺]_i) organized in space, time and amplitude have been known to be important in cell migration for some time, the sources of Ca²⁺ and the mechanism by which it modulates this process in cancer cells are only now beginning to be understood.
2. In general, Ca²⁺-dependent mechanisms of malignant migration do not seem to be very different from those that are evident in normal physiological migration, and thus searching for potential differences is quite a challenging task. The major differences seem to arise on a quantitative level owing to aberrant expression of Ca²⁺-handling proteins and/or Ca²⁺-dependent effectors, leading to the increased turnover of focal adhesions and more effective proteolysis of extracellular matrix components.
3. Recently, a number of known molecular players in cellular Ca²⁺ homeostasis, such as the Ca²⁺-permeable members of the transient receptor potential (TRP) channel family and the constituents of store-operated Ca²⁺ entry, calcium release-activated calcium channel protein 1 (ORAI1) and stromal interaction molecule 1 (STIM1), have been implicated in the development of the metastatic cell phenotype and tumour cell migration. The data linking specific TRP channels to cancer cell migration, invasion and metastasis are still largely phenomenological.
4. Ca²⁺-permeable ion channels might also be of use in determining prognosis, as the expression pattern of such channels, and the degree of their functionality, change with cancer progression.
5. Ca²⁺ signalling still constitutes a novel area of research in oncology. As this field is still rather young, not all the potential players have yet been investigated, and for those that have been studied, the specific roles in migration, invasion and metastasis of different types of cancers are only just beginning to be understood.

要点翻译：

1. 普遍存在的第二信使Ca2+是细胞迁移的关键调节因子。虽然人们早已了解细胞内Ca2+浓度（[Ca2+]i）在空间、时间和幅度上的协调变化对细胞迁移至关重要，但Ca2+的来源及其在癌细胞中调控该过程的机制直到最近才开始被揭示。
2. 总体而言，恶性迁移的Ca2+依赖性机制与正常生理性迁移中的机制似乎并无显著差异，因此寻找潜在区别是一项相当具有挑战性的任务。主要差异似乎体现在定量水平上，这是由于Ca2+处理蛋白和/或Ca2+依赖性效应物的异常表达，导致黏着斑周转加速和细胞外基质成分更有效的蛋白水解。
3. 最近研究发现，细胞Ca2+稳态中的多个已知分子参与者——例如瞬时受体电位（TRP）通道家族中的Ca2+渗透性成员，以及储存操纵性钙内流（SOCE）的组成元件：钙释放激活钙通道蛋白1（ORAI1）和基质相互作用分子1（STIM1）——与转移性细胞表型的形成及肿瘤细胞迁移密切相关。目前将特定TRP通道与癌细胞迁移、侵袭和转移相关联的研究数据仍主要停留在现象观察层面。
4. Ca2+渗透性离子通道或许还有助于判断预后，因为这类通道的表达模式及其功能程度会随着癌症进展而改变。
5. Ca2+信号传导在肿瘤学领域仍是一个新兴研究方向。由于该领域尚处于发展初期，并非所有潜在参与者都已被研究，而已被研究的分子在不同类型癌症的迁移、侵袭和转移中的具体作用也才刚刚被认识。

英文摘要：

In most cases, metastasis, not the primary tumour per se, is the main cause of mortality in cancer patients. In order to effectively escape the tumour, enter the circulation and establish secondary growth in distant organs cancer cells must develop an enhanced propensity to migrate. The ubiquitous second messenger Ca2+ is a crucial regulator of cell migration. Recently, a number of known molecular players in cellular Ca2+ homeostasis, including calcium release-activated calcium channel protein 1 (ORAI1), stromal interaction molecule 1 (STIM1) and transient receptor potential (TRP) channels, have been implicated in tumour cell migration and the metastatic cell phenotype. We discuss how these developments have increased our understanding of the Ca2+ dependence of pro-metastatic behaviours.

摘要翻译： 

在大多数情况下，导致癌症患者死亡的主因是肿瘤转移，而非原发肿瘤本身。为了有效脱离原发灶、进入循环并在远端器官定植，癌细胞必须获得更强的迁移能力。普遍存在的第二信使Ca²⁺是细胞迁移的关键调控因子。近期研究发现，多种Ca²⁺稳态相关分子——如钙释放激活钙通道蛋白1（ORAI1）、基质相互作用分子1（STIM1）及瞬时受体电位（TRP）通道——均参与肿瘤细胞的迁移及转移表型。本文将探讨这些进展如何深化我们对促转移行为Ca²⁺依赖性的理解。

原文链接：

Calcium in tumour metastasis: new roles for known actors