Abstract
Among the many factors involved in the maintenance of homeostatic growth is the tight regulation of cellular pH. Intracellular pH of normal cells is maintained within a physiological range thanks to the activity of a number of pH regulators that respond to the acidbase shifts associated with normal cellular metabolic processes. Interestingly, there is a preponderance of evidence that dysregulation of intracellular pH is associated with processes that favor cell transformation such as cell cycle progression, enhanced proliferation, insensitivity to growth inhibitory stimuli, resistance to apoptosis, genomic instability and angiogenesis. Among the strategies employed by the cells to regulate intracellular pH, the Na+/H+ exchanger 1 (NHE1) protein from the Na+/H+ exchanger (NHE) family has been directly associated with cellular transformation, invasion and metastasis. These observations have heightened the interest in NHE1 as a promising novel drug target for more effective and selective anti-cancer therapeutics. Here we present a review of the basic biology of this remarkable protein and present evidence to support targeting NHE1 as a potential anti-cancer strategy.
Keywords: NHE1, cancer therapy, homeostatic growth, cellular pH, apoptosis, genomic instability, angiogenesis, cellular transformation, invasion, metastasis
Current Pharmaceutical Design
Title: NHE-1: A Promising Target for Novel Anti-cancer Therapeutics
Volume: 18 Issue: 10
Author(s): Ser Yue Loo, Michelle Ker Xing Chang, Charis Sui Huay Chua, Alan Prem Kumar, Shazib Pervaiz and Marie Veronique Clement
Affiliation:
Keywords: NHE1, cancer therapy, homeostatic growth, cellular pH, apoptosis, genomic instability, angiogenesis, cellular transformation, invasion, metastasis
Abstract: Among the many factors involved in the maintenance of homeostatic growth is the tight regulation of cellular pH. Intracellular pH of normal cells is maintained within a physiological range thanks to the activity of a number of pH regulators that respond to the acidbase shifts associated with normal cellular metabolic processes. Interestingly, there is a preponderance of evidence that dysregulation of intracellular pH is associated with processes that favor cell transformation such as cell cycle progression, enhanced proliferation, insensitivity to growth inhibitory stimuli, resistance to apoptosis, genomic instability and angiogenesis. Among the strategies employed by the cells to regulate intracellular pH, the Na+/H+ exchanger 1 (NHE1) protein from the Na+/H+ exchanger (NHE) family has been directly associated with cellular transformation, invasion and metastasis. These observations have heightened the interest in NHE1 as a promising novel drug target for more effective and selective anti-cancer therapeutics. Here we present a review of the basic biology of this remarkable protein and present evidence to support targeting NHE1 as a potential anti-cancer strategy.
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Yue Loo Ser, Ker Xing Chang Michelle, Sui Huay Chua Charis, Prem Kumar Alan, Pervaiz Shazib and Veronique Clement Marie, NHE-1: A Promising Target for Novel Anti-cancer Therapeutics, Current Pharmaceutical Design 2012; 18 (10) . https://dx.doi.org/10.2174/138161212799504885
DOI https://dx.doi.org/10.2174/138161212799504885 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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