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Na+/H+ exchangers (NHEs) are a group of secondary active antiporters thatregulate cellular pH, cell volume and ion homeostasis. In humans, nine isoforms(NHE1-NHE9) were identified and characterized as functional NHEs. While a growingbody of evidence indicates that NHE1 generates an acidic tumor environment andthereby contributes to tumor invasion, little is known about the role of otherNHE isoforms in tumor progression. NHE7 is a unique member of the NHE gene familythat dynamically shuttles between the trans-Golgi network, endosomes and the plasmamembrane, and regulates the luminal pH of these organelles. Here we show thatNHE7-overexpression in breast cancer MDA-MB-231 cells enhances cell overlay, cell-celladhesion, invasion, anchorage-independent tumor growth and tumor formation in vivo.In contrast, NHE1-overexpression enhances tumor invasion, but it has little effecton cell adhesion or anchorage-independent tumor growth. Pathological examinationsof the tumor samples derived from NHE7-overexpressing cells showed a similar appearanceto aggressive tumors. Together, these results suggest that NHE7 enhances tumorprogression. This is the first report to show the involvement of an organellarNHE in oncogenic processes.

Organellar (Na+, K+)/H+ exchanger NHE7 regulates cell adhesion, invasion and anchorage-independent growth of breast cancer MDA-MB-231 cells