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

Nat Rev Cancer. 2005 Oct;5(10):786-95. doi: 10.1038/nrc1713.


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?

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cation Transport Proteins / chemistry
  • Cation Transport Proteins / physiology*
  • Humans
  • Hydrogen-Ion Concentration
  • Membrane Proteins / chemistry
  • Membrane Proteins / physiology*
  • Mice
  • Neoplasm Invasiveness
  • Neoplasm Metastasis*
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Signal Transduction
  • Sodium-Hydrogen Exchanger 1
  • Sodium-Hydrogen Exchangers / chemistry
  • Sodium-Hydrogen Exchangers / physiology*


  • Cation Transport Proteins
  • Membrane Proteins
  • SLC9A1 protein, human
  • Slc9a1 protein, mouse
  • Sodium-Hydrogen Exchanger 1
  • Sodium-Hydrogen Exchangers