Na(V)1.5 enhances breast cancer cell invasiveness by increasing NHE1-dependent H(+) efflux in caveolae

Oncogene. 2011 Apr 28;30(17):2070-6. doi: 10.1038/onc.2010.574. Epub 2010 Dec 20.

Abstract

Na(V)1.5 sodium channels enhance the invasiveness of breast cancer cells through the acidic-dependent activation of cysteine cathepsins. Here, we showed that the Na(+)/H(+) exchanger type 1 (NHE1) was an important regulator of H(+) efflux in breast cancer cells MDA-MB-231 and that its activity was increased by Na(V)1.5. Na(V)1.5 and NHE1 were colocalized in membrane rafts containing caveolin-1. The inhibition of Na(V)1.5 or NHE1 induced a similar reduction in cell invasiveness and extracellular matrix degradation; no additive effect was observed when they were simultaneously inhibited. Our study suggests that Na(V)1.5 and NHE1 are functionally coupled and enhance the invasiveness of cancer cells by increasing H(+) efflux.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biological Transport
  • Breast Neoplasms / pathology*
  • Cation Transport Proteins / genetics
  • Cation Transport Proteins / metabolism*
  • Caveolae / metabolism*
  • Cell Line, Tumor
  • Humans
  • Hydrogen-Ion Concentration
  • Intracellular Space / chemistry
  • Intracellular Space / metabolism
  • Muscle Proteins / genetics
  • Muscle Proteins / metabolism*
  • NAV1.5 Voltage-Gated Sodium Channel
  • Neoplasm Invasiveness
  • Protein Transport
  • Protons*
  • Sodium Channels / genetics
  • Sodium Channels / metabolism*
  • Sodium-Hydrogen Exchanger 1
  • Sodium-Hydrogen Exchangers / genetics
  • Sodium-Hydrogen Exchangers / metabolism*

Substances

  • Cation Transport Proteins
  • Muscle Proteins
  • NAV1.5 Voltage-Gated Sodium Channel
  • Protons
  • SCN5A protein, human
  • SLC9A1 protein, human
  • Sodium Channels
  • Sodium-Hydrogen Exchanger 1
  • Sodium-Hydrogen Exchangers