Down-regulation of Aquaporin-1 in W489 Colon Cancer Cells Inhibits Cell Migration

摘要

Recent studies have demonstrated that aquaporin (AQP) expression facilitates cell migration and promotes angiogenesis and neutrophil motility. Migration of tumor cells is a crucial step in tumor invasion and metastasis. In the present study, we investigated the expression of AQP in human W489 colon cancer cells and characterized its function in cell migration. Two populations of W489 cell clones with high (W489h) and low (W489l) AQP1 expression were identified by RT-PCR and Immunoblot analysis. Immunofluorescence indicated expression of AQP1 protein in the plasma membrane of W489 cells. W489 cell clones (W489h and W489l) with high and about 2.3 fold lower osmotic water permeability with corresponding high and low AQP1 expression were identified by functional assay. Seruminduced transwell migration rate of W489l (9.5±1.1%) was remarkably lower than that of W489h (28.9±0.9%). Wound healing assay demonstrated significantly decelerated wound closure in W489l cells as compared to W489h cells. RNA interference vector of AQP1 (AQP1i) effectively inhibited the mRNA and protein expression of AQP1 in W489h cells. Accordingly, relative plasma membrane water permeability, transwell migration rate and wound closure speed of W489h-AQP1i were reduced to the level similar to W489l cells. The results provided direct evidence that aquaporin-mediated plasma membrane water permeability plays an important role in colon cancer cell migration and may be associated with colon cancer invasion and metastasis.