title: Golgi phosphoprotein 2 (GOLPH2) is a novel bile acid-responsive modulator of oesophageal cell migration and invasion.
abstract: BACKGROUND
  The aetiology of Barrett's oesophagus (BO) and oesophageal cancer is poorly understood. We previously demonstrated that Golgi structure and function is altered in oesophageal cancer cells. A Golgi-associated protein, GOLPH2, was previously established as a tissue biomarker for BO. Cellular functions for GOLPH2 are currently unknown, therefore in this study we sought to investigate functional roles for this Golgi-associated protein in oesophageal disease.
  
  
  METHODS
  Expression, intracellular localisation and secretion of GOLPH2 were identified by immunofluorescence, immunohistochemistry and western blot. GOLPH2 expression constructs and siRNA were used to identify cellular functions for GOLPH2.
  
  
  RESULTS
  We demonstrate that the structure of the Golgi is fragmented and the intracellular localisation of GOLPH2 is altered in BO and oesophageal adenocarcinoma tissue. GOLPH2 is secreted by oesophageal cancer cells and GOLPH2 expression, cleavage and secretion facilitate cell migration and invasion. Furthermore, exposure of cells to DCA, a bile acid component of gastric refluxate and known tumour promoter for oesophageal cancer, causes disassembly of the Golgi structure into ministacks, resulting in cleavage and secretion of GOLPH2.
  
  
  CONCLUSIONS
  This study demonstrates that GOLPH2 may be a useful tissue biomarker for oesophageal disease. We provide a novel mechanistic insight into the aetiology of oesophageal cancer and reveal novel functions for GOLPH2 in regulating tumour cell migration and invasion, important functions for the metastatic process in oesophageal cancer.
authors.affiliation: Department of Clinical Medicine, Institute of Molecular Medicine, Trinity College, Dublin D08W9RT, Ireland.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Byrne
authors.affiliation: Department of Clinical Medicine, Institute of Molecular Medicine, Trinity College, Dublin D08W9RT, Ireland.
authors.forename: Spiros
authors.initials: S
authors.lastname: Bekiaris
authors.affiliation: Department of Clinical Medicine, Institute of Molecular Medicine, Trinity College, Dublin D08W9RT, Ireland.
authors.forename: Gina
authors.initials: G
authors.lastname: Duggan
authors.affiliation: Department of Clinical Medicine, Institute of Molecular Medicine, Trinity College, Dublin D08W9RT, Ireland.
authors.forename: David
authors.initials: D
authors.lastname: Prichard
authors.affiliation: Department of Clinical Medicine, Institute of Molecular Medicine, Trinity College, Dublin D08W9RT, Ireland.
authors.forename: Murat
authors.initials: M
authors.lastname: Kirca
authors.affiliation: Department of Histopathology, St James's Hospital, Dublin 8, Ireland.
authors.forename: Stephen
authors.initials: S
authors.lastname: Finn
authors.affiliation: Department of Surgery, Institute of Molecular Medicine, St James's Hospital, Trinity College, Dublin D08W9RT, Ireland.
authors.forename: John V
authors.initials: JV
authors.lastname: Reynolds
authors.affiliation: Faculty of Medicine, Department of Medicine, Imperial College London, London SW7 2AZ, UK.
authors.forename: Dermot
authors.initials: D
authors.lastname: Kelleher
authors.affiliation: Department of Clinical Medicine, Institute of Molecular Medicine, Trinity College, Dublin D08W9RT, Ireland.
authors.forename: Aideen
authors.initials: A
authors.lastname: Long
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D001471:Barrett Esophagus / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D001647:Bile Acids and Salts / Q000235:genetics* / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006056:Golgi Apparatus / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000235:genetics* / Q000473:pathology
chemical_list: D001647:Bile Acids and Salts; D014408:Biomarkers, Tumor; C410824:GOLM1 protein, human; D008565:Membrane Proteins