Decreased intracellular chloride enhances cell migration and invasion via activation of the ERK1/2 signaling pathway in DU145 human prostate carcinoma cells

Our previous study revealed that changes of the intracellular Cl-concentration ([Cl- ]i) affected cell proliferation in cancer cells. However, the role of Cl-on cell migration and invasion in cancer cells remains unanalyzed. Therefore, the aim of the present study is to investigate whether changes of [Cl- ]i affects cell migration and invasion of cancer cells. In human prostate cancer DU145 cells, cell migration and invasion were enhanced by culturing in the low Cl- medium (replacement of Cl- by NO3 - ). We also found that DU145 cells in the low Clcondition caused significant transient ERK1/2 activation followed by an increase of MMP-1 mRNA levels. Inhibition of ERK1/2 activation in the low Cl-condition reduced enhancement of MMP-1 mRNA levels and decreased cell migration and invasion. These observations indicate that [Cl- ]i plays important roles in metastatic function by regulating the ERK1/2 signaling pathway in human prostate cancer cells, and intracellular Cl-would be one of the key targets for anti-cancer therapy.