title: TGFβ-induced phosphorylation of Par6 promotes migration and invasion in prostate cancer cells.
abstract: BACKGROUND
  The Par complex - comprising partition-defective 6 (Par6), Par3, and atypical protein kinase C (aPKC) - is crucial for cell polarisation, the loss of which contributes to cancer progression. Transforming growth factor β (TGFβ)-induced phosphorylation of Par6 on the conserved serine 345 is implicated in epithelial-to-mesenchymal transition (EMT) in breast cancer. Here we investigated the importance of phosphorylated Par6 in prostate cancer.
  
  
  METHODS
  We generated a p-Par6(345)-specific antibody and verified its specificity in vitro. Endogenous p-Par6(345) was analysed by immunoblotting in normal human prostate RWPE1 and prostate cancer (PC-3U) cells. Subcellular localisation of p-Par6(345) in migrating TGFβ-treated PC-3U cells was analysed by confocal imaging. Invasion assays of TGFβ-treated PC-3U cells were performed. p-Par6 expression was immunohistochemically analysed in prostate cancer tissues.
  
  
  RESULTS
  TGFβ induced Par6 phosphorylation on Ser345 and its recruitment to the leading edge of the membrane ruffle in migrating PC-3U cells, where it colocalised with aPKCζ. The p-Par6-aPKCζ complex is important for cell migration and invasion, as interference with this complex prevented prostate cancer cell invasion. High levels of activated Par6 correlated with aggressive prostate cancer.
  
  
  CONCLUSIONS
  Increased p-Par6Ser(345) levels in aggressive prostate cancer tissues and cells suggest that it could be a useful novel biomarker for predicting prostate cancer progression.
authors.affiliation: Pathology Section, Department of Medical Biosciences, Umeå University, Umeå SE-901 85, Sweden.
authors.forename: Y
authors.initials: Y
authors.lastname: Mu
authors.affiliation: Pathology Section, Department of Medical Biosciences, Umeå University, Umeå SE-901 85, Sweden.
authors.forename: G
authors.initials: G
authors.lastname: Zang
authors.affiliation: Ludwig Institute for Cancer Research, Uppsala University, Uppsala SE-751 24, Sweden.
authors.forename: U
authors.initials: U
authors.lastname: Engström
authors.affiliation: Rudbeck Laboratory, Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala SE-751 85, Sweden.
authors.forename: C
authors.initials: C
authors.lastname: Busch
authors.affiliation: Pathology Section, Department of Medical Biosciences, Umeå University, Umeå SE-901 85, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Landström
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D015331:Cohort Studies; D006801:Humans; D008297:Male; D009361:Neoplasm Invasiveness; D010766:Phosphorylation; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C499657:PARD6A protein, human; D016212:Transforming Growth Factor beta