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Review

Nature Reviews Cancer 5, 786–795 (1 October 2005) | doi:10.1038/nrc1713

The role of disturbed pH dynamics and the Na+/H+ exchanger in metastasis

Rosa A. Cardone , Valeria Casavola & Stephan J. Reshkin

Recent research has highlighted the fundamental role of the tumour's extracellular metabolic microenvironment in malignant invasion. This microenvironment is acidified primarily by the tumour-cell Na+/H+ exchanger NHE1 and the H+/lactate cotransporter, which are activated in cancer cells. NHE1 also regulates formation of invadopodia — cell structures that mediate tumour cell migration and invasion. How do these alterations of the metabolic microenvironment and cell invasiveness contribute to tumour formation and progression?