pH sensing and regulation in cancer.
pH sensing and regulation in cancer.
复制标题
癌症中的pH感应和调节。
DOI：
10.3389/fphys.2013.00370
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发表时间：
2013-12-17
影响因子：
4
通讯作者：
Gillies RJ
中科院分区：
文献类型：
--
作者：
Damaghi M;Wojtkowiak JW;Gillies RJ
细胞通过控制膜质子泵和转运体将细胞内的pH(Phi)维持在一个狭窄的范围内(7.1-7.2)，膜质子泵和转运体的活性由细胞质内的pH传感器设定。这些传感器具有识别和诱导细胞反应以维持phi的能力，通常以酸化细胞外pH为代价。反过来，胞外酸化通过特定的酸敏感离子通道(ASIC)和质子敏感G蛋白偶联受体(GPCRs)影响细胞。在这篇综述中，我们将讨论质膜质子感应的一些主要参与者及其下游对癌细胞的影响，以及这些pH介导的变化如何影响迁移和转移等过程。它们将酸性pH信号传递到细胞质和细胞核的复杂机制尚不清楚。然而，有证据表明，质子敏感的GPCRs如GPR4、TDAG8和OGR1的表达可以调节肿瘤的发生和侵袭，包括cofilin和talin调节的肌动蛋白(de-)聚合。维持phi稳态的主要机制包括单羧酸盐、碳酸氢盐和质子转运体。值得注意的是，几乎没有证据表明它们的活动与细胞外H+感受器的活动之间存在联系，这表明细胞内和细胞外pH之间存在机械上的脱节。了解pH感知和调节的机制可能会导致针对酸中毒的新颖和知情的治疗策略，酸中毒是实体肿瘤的常见物理特征。
Cells maintain intracellular pH (pHi) within a narrow range (7.1–7.2) by controlling membrane proton pumps and transporters whose activity is set by intra-cytoplasmic pH sensors. These sensors have the ability to recognize and induce cellular responses to maintain the pHi, often at the expense of acidifying the extracellular pH. In turn, extracellular acidification impacts cells via specific acid-sensing ion channels (ASICs) and proton-sensing G-protein coupled receptors (GPCRs). In this review, we will discuss some of the major players in proton sensing at the plasma membrane and their downstream consequences in cancer cells and how these pH-mediated changes affect processes such as migration and metastasis. The complex mechanisms by which they transduce acid pH signals to the cytoplasm and nucleus are not well understood. However, there is evidence that expression of proton-sensing GPCRs such as GPR4, TDAG8, and OGR1 can regulate aspects of tumorigenesis and invasion, including cofilin and talin regulated actin (de-)polymerization. Major mechanisms for maintenance of pHi homeostasis include monocarboxylate, bicarbonate, and proton transporters. Notably, there is little evidence suggesting a link between their activities and those of the extracellular H+-sensors, suggesting a mechanistic disconnect between intra- and extracellular pH. Understanding the mechanisms of pH sensing and regulation may lead to novel and informed therapeutic strategies that can target acidosis, a common physical hallmark of solid tumors.
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影响因子：
6.4
作者：
Boedtkjer, Ebbe;Moreira, Jose M. A.;Aalkjaer, Christian
通讯作者：
Aalkjaer, Christian
DOI：
10.1038/nrc2646
发表时间：
2009-07
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
通讯作者：
--
影响因子：
4.8
作者：
Barneaud-Rocca, Damien;Borgese, Franck;Guizouarn, Helene
通讯作者：
Guizouarn, Helene
影响因子：
5.5
作者：
Boedtkjer, Ebbe;Damkier, Helle H.;Aalkjaer, Christian
通讯作者：
Aalkjaer, Christian
影响因子：
4
作者：
Chen, Hongmin;Wang, Li;Li, Yong
通讯作者：
Li, Yong