Subcellular localization of aquaporin 3 in prostate cancer is regulated by RalA

Chen,Qiwei; Zhu,Liang; Zong,Huafeng; Song,Xishuang; Wang,Lina; Wang,Xuejian; Yang,Deyong; Wang,Jianbo

doi:10.3892/or.2018.6308

Subcellular localization of aquaporin 3 in prostate cancer is regulated by RalA

Authors:
- Qiwei Chen
- Liang Zhu
- Huafeng Zong
- Xishuang Song
- Lina Wang
- Xuejian Wang
- Deyong Yang
- Jianbo Wang
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Affiliations: Department of Urology, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China, Department of Physiology, Dalian Medical University, Dalian, Liaoning 116000, P.R. China, Department of Pathology, Dalian Municipal Friendship Hospital, Dalian, Liaoning 116000, P.R. China
Published online on: March 9, 2018 https://doi.org/10.3892/or.2018.6308
Pages: 2171-2177

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Abstract

We previously found that in normal epithelia of the prostate, localization of AQP3 is limited to the cell membranes; however, the expression of AQP3 protein in cancer epithelia is distributed to the plasma. Yet, the detailed mechanism remains unclear. In the present study, PC‑3 cell derivatives with stable knockdown of RAS like proto‑oncogene A (RalA) and overexpression of E‑cadherin were established. We found that overexpression of E‑cadherin and knockdown of RaLA resulted in an increase in AQP3 in prostate cancer cell plasma membranes. In order to investigate the functions caused by of the AQP3 redistribution in prostate cancer cells, the growth function of AQP3 redistribution was detected with clonogenic, MTT and MTS assays. In regards to the effect on apoptosis, flow cytometric analysis and DNA Ladder TUNEL assay were utilized. The results showed that AQP3 redistribution in PC‑3 cells significantly inhibited the proliferation of cells and enhanced cell apoptosis compared with these parameters in the control. Wound healing assay and Matrigel assays determined that knockout of RalA inhibited the motility and invasion capability of PC‑3 cells. To investigate the molecular mechanism involved in AQP3 redistribution in PC‑3 cells, the level of cAMP in PC‑3 cells was examined, and the results showed that AQP3 distribution was regulated through cAMP/PKA/RalA signal pathways. In conclusion, these studies suggest a novel function of AQP3, and provide a creative view for RalA-directed therapies.

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