Aquaporin 8 involvement in human cervical cancer SiHa migration via the EGFR-Erk1/2 pathway.

Yong-Hua Shi,Talaf Tuokan,Chen Lin,Heng Chang

doi:10.7314/apjcp.2014.15.15.6391

Abstract

Overexpression of aquaporins (AQPs) has been reported in several human cancers. Epidermal growth factor receptor (EGFR)-extracellular signal-regulated kinases 1/2 (Erk1/2) are associated with tumorigenesis and cancer progression and may upregulate AQP expression. In this study, we demonstrated that EGF (epidermal growth factor) induces SiHa cells migration and AQP8 expression. Wound healing results showed that cell migration was increased by 2.79-1.50-fold at 24 h and 48 h after EGF treatment. AQP8 expression was significantly increased (3.33-fold) at 48 h after EGF treatment in SiHa cells. An EGFR kinase inhibitor, PD153035, blocked EGF-induced AQP8 expression and cell migration and AQP8 expression was decreased from 1.59-fold (EGF-treated) to 0.43-fold (PD153035-treated) in SiHa. Furthermore, the MEK (MAPK (mitogen-activated protein kinase)/Erk (extracellular signal regulated kinase)/Erk inhibitor U0126 also inhibited EGF-induced AQP8 expression and cell migration. AQP8 expression was decreased from 1.21-fold (EGF-treated) to 0.43-fold (U0126-treated). Immunofluorescence microscopy further confirmed the results. Collectively, our findings show that EGF induces AQP8 expression and cell migration in human cervical cancer SiHa cells via the EGFR/Erk1/2 signal transduction pathway.

Highlights

The cells of all living organisms are composed mainly of water, which is essential for the existence of life on the planet
EGF induces cell migration in SiHa cells Invasion of malignant tumors is correlated with cell migration, we tested the capacity of EGF to induce migration in SiHa cells
Some experiments demonstrated that AQP8 contributed to tumor cell migration and proliferation (Shi et al, 2013; Zhu et al, 2013), while some research reported that AQP8 induced to tumor cell apoptosis and its expression was downregulated in carcinoma (Fischer et al, 2001; Jablonski et al, 2007)

Summary

Introduction

The cells of all living organisms are composed mainly of water, which is essential for the existence of life on the planet. Aquaporins (AQPs) are small transmembrane proteins that are expressed in a variety of epithelial tissues where they are responsible for regulating rapid water movement across epithelial barriers driven by osmotic gradients. Based on their permeability, mammalian AQPs are divided into three groups: a) water-selective permeable aquaporins (AQP0, AQP1, AQP2, AQP4, AQP5, AQP6, and AQP8); B) aquaglyceroporins permeable to water, glycerol, urea, and other solutes (AQP3, AQP7, AQP9, and AQP10); C) subcellular aquaporins or super-aquaporins (AQP11 and AQP12), which have low homology with the other AQPs (Murai-Hatano et al, 2008). It is important to elucidate their tumorspecific expression patterns and to reveal their potential functions besides sole water transport in the different organs and tumor entities

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