Inserm U921, Nutrition, Croissance et Cancer, Université François Rabelais, Faculté de Médecine, Tours, France.
Oncogene. 2011 Apr 28;30(17):2070-6. doi: 10.1038/onc.2010.574. Epub 2010 Dec 20.
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.
钠通道增强乳腺癌细胞的侵袭性通过酸性依赖激活半胱氨酸组织蛋白酶。在这里，我们表明钠/氢交换器 1 型（NHE1）是乳腺癌细胞 MDA-MB-231 中 H+外排的重要调节剂，其活性被钠通道增强。钠通道和 NHE1 共定位于含有窖蛋白-1的膜筏中。钠通道的抑制或 NHE1 的抑制诱导细胞侵袭性和细胞外基质降解的相似降低；当它们同时被抑制时，没有观察到相加效应。我们的研究表明，钠通道和 NHE1 是功能偶联的，并通过增加 H+外排来增强癌细胞的侵袭性。
