Cancer and pH Dynamics: Transcriptional Regulation, Proteostasis, and the Need for New Molecular Tools
| Autor: | Katharine A. White, Keelan J Trull, Ricardo Romero-Moreno, Brandon J Czowski |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cancer Research Intracellular pH Review Tumor initiation Biology molecular tools medicine.disease_cause lcsh:RC254-282 03 medical and health sciences 0302 clinical medicine medicine Transcriptional regulation cancer proteostasis Cell migration biosensors lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Review article tumorigenesis 030104 developmental biology Proteostasis Oncology pH regulation 030220 oncology & carcinogenesis Cancer cell Carcinogenesis transcription Neuroscience |
| Zdroj: | Cancers, Vol 12, Iss 2760, p 2760 (2020) Cancers |
| ISSN: | 2072-6694 |
| Popis: | Simple Summary 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. Abstract 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. |
| Databáze: | OpenAIRE |
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