NHE-1: a promising target for novel anti-cancer therapeutics

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.