title: Aquaporin 3 promotes prostate cancer cell motility and invasion via extracellular signal-regulated kinase 1/2-mediated matrix metalloproteinase-3 secretion.
abstract: Aquaporins (AQPs) are known to be important in cancer progression. The present study used a cDNA microarray to demonstrate that AQP3, a member of the AQP family, was overexpressed in prostate cancer cells. In order to determine the role of AQP3 in prostate cancer, AQP3 expression was silenced by transfection with small interfering RNA, following which wound healing and invasion assays were conducted in DU‑145 and PC‑3 cells. Notably, the results showed that silencing of AQP3 suppressed prostate cancer cell motility and invasion. The possible mechanisms underlying the AQP3‑enhanced motility and invasion of prostate cancer cells was also investigated. Knockdown of AQP3 expression was shown to reduce extracellular signal‑regulated kinase 1/2 (ERK1/2) activation in DU‑145 and PC‑3 cells. Blocking the ERK pathway inhibited AQP3‑mediated motility and invasion of these cells. Finally, the results demonstrated that AQP3 upregulated matrix metalloproteinase‑3 (MMP‑3) expression and secretion in prostate cancer cells via activation of the ERK pathway. In conclusion, the present study suggests that AQP3 induces ERK1/2 activation, thereby increasing MMP‑3 expression and secretion, which in turn promotes prostate cancer cell motility and invasion. Thus, AQP3 may be considered to be a potential therapeutic target for prostate cancer.
authors.affiliation: Department of Urology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Urology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. China.
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Urology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. China.
authors.forename: Danfeng
authors.initials: D
authors.lastname: Xu
authors.affiliation: Department of Urology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. China.
authors.forename: Yushan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Urology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Gao
mesh_terms: D051400:Aquaporin 3 / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D016000:Cluster Analysis; D015870:Gene Expression; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020935:MAP Kinase Signaling System; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism*
chemical_list: D051400:Aquaporin 3; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D019278:Matrix Metalloproteinase 3