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

作者：Brisson L; Gillet L; Calaghan S; Besson P; Le Guennec J Y; Roger S^*; Gore J

来源：Oncogene, 2011, 30(17): 2070-2076.

DOI：10.1038/onc.2010.574

• cancer
• caveolae
• invasion
• Na (broken vertical bar)/H (broken vertical bar) exchanger
• voltage-gated sodium channels

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 NaV1.5 and NHE1 are functionally coupled and enhance the invasiveness of cancer cells by increasing H+ efflux. Oncogene (2011) 30, 2070-2076; doi:10.1038/onc.2010.574; published online 20 December 2010

• 出版日期2011-4