Question: 

The Na⁺/H⁺ exchanger NHE1 has been implicated in control of cell motility (1,2), yet the mechanisms involved and the roles of other acid-extruding transporters remain incompletely understood. Here, we address the roles of NHE1 and the Na+-HCO3- cotransporter NBCn1 in motility of MCF7 breast cancer cells expressing a truncated, constitutively active ErbB2 receptor (?NErbB2) associated with increased metastasis and poor prognosis.

Methods: 

Cells were serum-starved for 48 h to partially simulate the tumor microenvironment. Protein expression was assessed using qPCR and Western blotting; intra- and pericellular pH by quantification of the fluorescence of BCECF and fluorescein-conjugated WGA, respectively; 2D motility and adhesion as described (1,2); and invasion using Neuroprobe chemotaxis chambers.

Results: 

?NErbB2 expression was associated with increased activities of ERK1/2, its effector p90RSK, and Akt, upregulation of NBCn1, Ser703-phosphorylation of NHE1, and NHE1-inhibitor (EIPA)-sensitive pericellular acidification. Adhesion and migration of serum-starved cells on collagen I were augmented by ?NErbB2 expression. Both processes were inhibited by ~50% by the RSK inhibitor SL0101, unaffected by the NBC inhibitor S0859, and, unexpectedly, further stimulated by EIPA. Invasion through collagen I and basal lamina was augmented by ?NErbB2 expression and was unaffected by EIPA in basal lamina.

Conclusion: 

In serum-starved ?NErbB2-expressing MCF-7 cells, NHE1 appears to play a negative rather than stimulatory role in adhesion and 2D cell motility. 1. Stock, Gassner, Hauck, Arnold, Mally, Eble, Dieterich, Schwab (2005) J Physiol 567, 225–238. 2. Schneider, Stock, Dieterich, Jensen, Pedersen, Satir, Schwab, Christensen, Pedersen (2009) J. Cell Biol. 185, 163–176