Cancer and pH Dynamics: Transcriptional Regulation, Proteostasis, and the Need for New Molecular Tools.
Cancer and pH Dynamics: Transcriptional Regulation, Proteostasis, and the Need for New Molecular Tools.
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DOI：
10.3390/cancers12102760
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发表时间：
2020-09-25
期刊：
影响因子：
5.2
通讯作者：
White KA
中科院分区：
文献类型：
--
作者：
Czowski BJ;Romero-Moreno R;Trull KJ;White KA
随着肿瘤的生长，癌细胞必须克服旨在控制细胞生长的正常信号。大多数癌细胞通过关闭阻止生长的蛋白质或打开通过突变刺激生长的蛋白质来做到这一点，但也通过改变细胞内这些蛋白质的水平来实现这一点。这篇综述文章综述了最近的研究，这些研究表明，癌细胞内环境的酸碱性(PH)可能允许癌细胞特别稳定帮助它们生长的蛋白质，并移除导致细胞死亡的蛋白质。我们还讨论了新的研究工具，使我们能够测量和操纵细胞中的pH值，以更好地了解pH值在促进癌症生长和进展中所起的作用。癌细胞的一个新特点是pH动态失调。最近的工作表明，细胞内pH(Phi)动力学的失调使肿瘤细胞在种群水平上表现出不同的行为，包括细胞增殖、细胞迁移和转移、逃避凋亡和代谢适应。然而，驱动pH依赖的癌症相关细胞行为的分子机制在很大程度上是未知的。在这篇综述文章中，我们探索了最近的文献，这些文献表明PHI动力学可能在分子水平上调节或加强致癌转录和蛋白恒定变化，并讨论了在肿瘤发生和肿瘤异质性方面的结果。我们讨论的大多数数据都是种群水平的分析；缺乏单细胞数据是因为缺乏工具来通过时空控制来实验性地改变PHI。关于Phi动力学如何在复杂的体内微环境中发挥作用的数据也很稀少。为了满足这一需求，在这篇综述的最后，我们介绍了在单细胞分辨率下活细胞PHI测量的最新进展。我们还讨论了工具开发在揭示PHI动力学驱动肿瘤启动、进展和转移的机制中的重要作用。
As tumors grow, cancer cells must overcome the normal signals designed to keep cell growth in check. Most cancer cells do this by turning off proteins that prevent growth or turning on proteins that stimulate growth through mutation but also through changes in the levels of these proteins inside cells. This review article summarizes recent research that suggests the acidity or basicity (pH) of the environment inside cancer cells may allow cancer cells to specifically stabilize proteins that help them grow and remove proteins that induce cell death. We also discuss new research tools that allow us to measure and manipulate pH in cells to better understand the role pH plays in enhancing cancer growth and progression. An emerging hallmark of cancer cells is dysregulated pH dynamics. Recent work has suggested that dysregulated intracellular pH (pHi) dynamics enable diverse cancer cellular behaviors at the population level, including cell proliferation, cell migration and metastasis, evasion of apoptosis, and metabolic adaptation. However, the molecular mechanisms driving pH-dependent cancer-associated cell behaviors are largely unknown. In this review article, we explore recent literature suggesting pHi dynamics may play a causative role in regulating or reinforcing tumorigenic transcriptional and proteostatic changes at the molecular level, and discuss outcomes on tumorigenesis and tumor heterogeneity. Most of the data we discuss are population-level analyses; lack of single-cell data is driven by a lack of tools to experimentally change pHi with spatiotemporal control. Data is also sparse on how pHi dynamics play out in complex in vivo microenvironments. To address this need, at the end of this review, we cover recent advances for live-cell pHi measurement at single-cell resolution. We also discuss the essential role for tool development in revealing mechanisms by which pHi dynamics drive tumor initiation, progression, and metastasis.
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影响因子：
4.6
作者：
Deschamps, Antoine;Colinet, Anne-Sophie;Morsomme, Pierre
通讯作者：
Morsomme, Pierre
影响因子：
6.4
作者：
Fahmy, Karim;Gonzalez, Arnaud;Peulen, Olivier
通讯作者：
Peulen, Olivier
影响因子：
2.8
作者：
Dey, Simli;Bielytskyi, Pavlo;Madhu, P. K.
通讯作者：
Madhu, P. K.
DOI：
10.1083/jcb.201302131
发表时间：
2013-09-16
期刊：
The Journal of cell biology
影响因子：
--
作者：
Choi CH;Webb BA;Chimenti MS;Jacobson MP;Barber DL
通讯作者：
Barber DL
Smad5 作为细胞内 pH 信使并维持生物能稳态
影响因子：
44.1
作者：
Fang Y;Liu Z;Chen Z;Xu X;Xiao M;Yu Y;Zhang Y;Zhang X;Du Y;Jiang C;Zhao Y;Wang Y;Fan B;Terheyden-Keighley D;Liu Y;Shi L;Hui Y;Zhang X;Zhang B;Feng H;Ma L;Zhang Q;Jin G;Yang Y;Xiang B;Liu L;Zhang X
通讯作者：
Zhang X