Golgi phosphoprotein 2 (GOLPH2) is a novel bile acid-responsive modulator of oesophageal cell migration and invasion

File Type:
PDFItem Type:
Journal ArticleDate:
2015Access:
openAccessCitation:
Anne-Marie Byrne, Spiros Bekiaris, Gina Duggan, David Prichard, Murat Kirca, Stephen Finn, John V Reynolds, Dermot Kelleher and Aideen Long, Golgi phosphoprotein 2 (GOLPH2) is a novel bile acid-responsive modulator of oesophageal cell migration and invasion, British Journal of Cancer, 113, 2015, 1332?1342Download Item:
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, immunohis-
tochemistry 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
Sponsor
Grant Number
Irish Cancer Society
CRF12BYR
Author's Homepage:
http://people.tcd.ie/byrnea13http://people.tcd.ie/longai
http://people.tcd.ie/reynoljv
http://people.tcd.ie/finns
Description:
PUBLISHEDType of material:
Journal ArticleCollections
Series/Report no:
British Journal of Cancer113
Availability:
Full text availableKeywords:
Barrett’s oesophagusSubject (TCD):
Cancer , Anticancer therapies , CANCER DEVELOPMENT , CANCER INVASION , CANCER TREATMENT , Cancer diagnosis , Cancer genetics and cell biology including metastasis , EPITHELIAL-CELLS , ESOPHAGEAL CANCER , Gastroenterology , Membrane and protein trafficking , Physiology , UPPER GASTROINTESTINAL CANCER , cancer prevention , colon cancerDOI:
http://dx.doi.org/10.1038/bjc.2015.350Metadata
Show full item recordLicences: