Aquaporin‐1 activity of plasma membrane affects HT20 colon cancer cell migration

Abstract

SummaryRecent studies revealed an important role of aquaporins (AQPs) in cell migration and migration-associated cell function such as angiogenesis, wound healing, 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 AQP1 in human HT20 colon cancer cells and characterized its function in cell migration. By reverse transcription-polymerase chain reaction (RT-PCR) and immunoblot analysis, expression of AQP1 was identified in HT20 cell lines. Immunofluorescence analysis indicated expression of AQP1 protein in the plasma membrane of HT20 cells. The recombinant adenovirus expressing human AQP1 increased the mRNA and protein expression of AQP1 in HT20 cells. In contrary, the RNA interference vector of AQP1 effectively inhibited the mRNA and protein expression of AQP1 in HT20 cells. Adenovirus-mediated high expression of AQP1 in HT20 cells increased relative plasma membrane water permeability and migration rate in both wound healing and invasive transwell migration assays. In contrary, RNA interference vector-mediated low expression of AQP1 in HT20 cells reduced relative plasma membrane water permeability and migration rate. AQP1 expression induced relocalization of actin protein and activation of RhoA and Rac. In nude mice, AQP1 increased extravasation of HT20 Cells in lung after tail vein injection. The results provided the 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.

Expression of aquaporin-1 is a poor prognostic factor for stage II and III colon cancer

“…Recently, various studies have focused on the association of AQPs and cancer (10)(11)(12)(13)(14)(15)(16)(17). AQP1 is expressed in vascular endothelial cells throughout the body, except in the normal central nervous, genital and lymphoid systems.…”

“…In addition, Moon et al (10) reported that AQP1 was associated with colorectal carcinogenesis and Yiang (12) reported that the AQP1 activity in plasma membranes affected HT20 colon cancer cell migration in vitro. Those findings revealed that the expression of AQP1 is associated with tumor progression in colon cancer.…”

“…It was reported that several types of cancer express AQP1 and it may be involved in carcinogenesis (10,11). An in vitro study demonstrated that AQP1-mediated plasma membrane water permeability is crucial for colon cancer cell migration and may be associated with tumor invasion and metastasis (12). However, available data on the clinical significance of AQP1 in colon cancer are limited.…”

Preparation of Microspheres Encapsulating a Recombinant TIMP-1 Adenovirus and their Inhibition of Proliferation of Hepatocellular Carcinoma Cells

“…Adenovirus vector was a common virus vector in gene therapy (Benlahrech et al, 2009;Jiang, 2009). It had many advantages, such as strong infection ability, high titer, efficient multicopy, no insertional mutagenesis, no genetic toxicity, etc.…”

Bumetanide Derivatives AqB007 and AqB011 Selectively Block the Aquaporin-1 Ion Channel Conductance and Slow Cancer Cell Migration

“…Although the precise mechanism for AQP1-enhanced motility remains unknown, both ion and water channels are essential in the cellular migration process (Schwab et al, 2007). AQP1 expression has been linked to metastasis and invasiveness of colon cancer cells (Jiang, 2009;Yoshida et al, 2013). In mammary and melanoma cancer cells, AQP1 facilitates tumor cell migration in vitro and metastasis in vivo (Hu and Verkman, 2006).…”