title: Aquaporin3 is required for FGF-2-induced migration of human breast cancers.
abstract: OBJECTIVE
  The aquaporin (AQP) family consists of a number of small integral membrane proteins that transport water and glycerol. AQPs are critical for trans-epithelial fluid transport. Recent reports demonstrated that AQPs, particularly AQP1 and AQP5, are expressed in high grade tumor cells of a variety of tissue origins, and that AQPs are involved in cell migration and metastasis. Based on this background, we examined whether AQP3, another important member of the AQP family, could facilitate cell migration in human breast cancers.
  
  
  METHODS
  Potential role of AQP3 was examined using two representative breast cancer cell lines (MDA-MB-231 and Bcap-37). Briefly, AQP3 expression was inhibited with a lentivirus construct that stably expressed shRNA against the AQP3 mRNA. AQP3 expression inhibition was verified with Western blot. Cell migration was examined using a wound scratch assay in the presence of fibroblast growth factor-2 (FGF-2). In additional experiments, AQP3 was inhibited by CuSO4. Fibroblast growth factor receptor (FGFR) kinase inhibitor PD173074, PI3K inhibitor LY294002, and MEK1/2 inhibitor PD98059 were used to dissect the molecular mechanism of FGF-2 induced AQP3 expression.
  
  
  RESULTS
  FGF-2 treatment increased AQP3 expression and induced cell migration in a dose dependent manner. Silencing AQP3 expression by a lentiviral shRNA inhibited FGF-2 induced cell migration. CuSO4, a water transport inhibitor selective for AQP3, also suppressed FGF-2-induced cell migration. The FGFR kinase inhibitor PD173074, significantly inhibited FGF-2-induced AQP3 expression and cell migration. The PI3K inhibitor LY294002 and MEK1/2 inhibitor PD98059 inhibited, but not fully blocked, FGF-2-induced AQP3 expression and cell migration.
  
  
  CONCLUSIONS
  AQP3 is required for FGF-2-induced cell migration in cultured human breast cancer cells. Our findings also suggest the importance of FGFR-PI3K and FGFR-ERK signaling in FGF-2-induced AQP3 expression. In summary, our findings suggest a novel function of AQP3 in cell migration and metastasis of breast cancers.
authors.affiliation: National Key Laboratory of Breast Cancer Prevention and Treatment, Cancer Institute and Hospital, Tianjin, China.
authors.forename: Xu-Chen
authors.initials: XC
authors.lastname: Cao
authors.forename: Wei-Ran
authors.initials: WR
authors.lastname: Zhang
authors.forename: Wen-Feng
authors.initials: WF
authors.lastname: Cao
authors.forename: Bo-Wen
authors.initials: BW
authors.lastname: Liu
authors.forename: Fei
authors.initials: F
authors.lastname: Zhang
authors.forename: Hong-Meng
authors.initials: HM
authors.lastname: Zhao
authors.forename: Ran
authors.initials: R
authors.lastname: Meng
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.forename: Rui-Fang
authors.initials: RF
authors.lastname: Niu
authors.forename: Xi-Shan
authors.initials: XS
authors.lastname: Hao
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
mesh_terms: D051400:Aquaporin 3 / Q000235:genetics / Q000378:metabolism*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D019327:Copper Sulfate / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D020868:Gene Silencing; D006801:Humans; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D034622:RNA Interference; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014161:Transduction, Genetic
chemical_list: D017468:Receptors, Fibroblast Growth Factor; D016222:Fibroblast Growth Factor 2; D051400:Aquaporin 3; D019869:Phosphatidylinositol 3-Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D019327:Copper Sulfate