Regulation of colon cancer cell migration and invasion by CLIC1-mediated RVD.

The metastasis of colorectal cancer is one of the most common causes of death in the world. In this investigation, we used the human colon cancer cell lines LOVO and HT29 as model systems to determine the role of the chloride intracellular channel 1 (CLIC1) in the metastasis of colonic cancer. In the present study, we found that regulatory volume decrease (RVD) capacity was markedly up-regulated in LOVO cells, which are characterized by a high metastatic potential. Functionally suppressing CLIC1 using the specific chloride intracellular channel 1 blocker Indanyloxyacetic acid 94 inhibited RVD and decreased the migration and invasion of colon cancer cells. Moreover, these effects occurred in a dose-dependent manner. The migration and invasion abilities in two cell lines also were inhibited by the knockdown of CLIC1 using small interfering RNA transfection. The mRNA and protein expression of CLIC1 is up-regulated in LOVO cells. In human colon cancer cells, CLIC1 is primarily located in the plasma membrane, where it functions as a chloride channel. Taken together, the results suggest that CLIC1 modulates the metastasis of colon cancer through its RVD-mediating chloride channel function. This study demonstrates, for the first time, that CLIC1 regulates the migration and invasion of colon cancer.