文章：

钙和癌症：靶向Ca²⁺运输

Calcium and cancer: targeting Ca²⁺ transport

原文发布日期：2007-07-01

DOI: 10.1038/nrc2171

类型: Review Article

开放获取: 否

要点：

1. Ca²⁺ homeostasis controls various cellular processes, including those relevant to tumorigenesis, such as proliferation, apoptosis, gene transcription and angiogenesis.
2. Ca²⁺ channels, pumps and exchangers control the complex and tight regulation of Ca²⁺ homeostasis. Specific isoforms of these proteins are responsible for increasing or reducing cytosolic free Ca²⁺. These channels, pumps and exchangers differ in their cellular distribution and their mechanism of transport.
3. Some cancers are associated with the up- or downregulation of specific Ca²⁺ channels or pumps. For example, TRPM8 is upregulated in prostate cancer and SERCA3 is downregulated in colon cancer.
4. Many Ca²⁺ channels, pumps and exchangers are modulated by pharmacological agents and are regarded as druggable. The role of Ca²⁺ in both proliferation and apoptosis means that both inhibitors and activators of these proteins are potential therapeutic agents in cancer chemotherapy.
5. Questions remain as to which approach, and what channels and pumps, are likely to lead to the most effective cancer therapeutics.

要点翻译：

1. 钙离子稳态调控多种细胞过程，包括与肿瘤发生相关的增殖、凋亡、基因转录及血管生成等过程。
2. 钙离子通道、泵和交换器共同实现对钙离子稳态的复杂精密调控。这些蛋白的特定亚型负责升高或降低胞浆游离钙离子浓度，其细胞分布与转运机制各不相同。
3. 特定钙通道或钙泵的表达异常与某些癌症的发生相关。例如TRPM8在前列腺癌中表达上调，而SERCA3在结肠癌中表达下调。
4. 多数钙离子通道、泵和交换器可被药物调控，被视为潜在药物靶点。鉴于钙离子在细胞增殖与凋亡中的双重作用，这些蛋白的抑制剂和激活剂均可能成为肿瘤化疗的潜在治疗策略。
5. 当前核心问题在于：何种干预策略以及针对哪些通道和泵的调控，能够导向最有效的癌症治疗手段。

英文摘要：

Ca²⁺ is a ubiquitous cellular signal. Altered expression of specific Ca²⁺ channels and pumps are characterizing features of some cancers. The ability of Ca²⁺ to regulate both cell death and proliferation, combined with the potential for pharmacological modulation, offers the opportunity for a set of new drug targets in cancer. However, the ubiquity of the Ca²⁺ signal is often mistakenly presumed to thwart the specific therapeutic targeting of proteins that transport Ca²⁺. This Review presents evidence to the contrary and addresses the question: which Ca²⁺ channels and pumps should be targeted?

摘要翻译： 

Ca²⁺是一种普遍存在的细胞信号。特定Ca²⁺通道和泵的表达改变是某些癌症的特征。Ca²⁺既能调控细胞死亡，又能调控细胞增殖，再加上其可被药物调控的潜力，为癌症治疗提供了一组新的药物靶点。然而，Ca²⁺信号的普遍性常被误认为会阻碍对Ca²⁺转运蛋白的特异性治疗靶向。本综述提出了相反的证据，并探讨了一个问题：应靶向哪些Ca²⁺通道和泵？

原文链接：

Calcium and cancer: targeting Ca2+ transport