Journal Article


R O'Connor
V Ayllon
D Papkovsky
A Zhadanov
J O'Keeffe
F M Fogarty



mcf 7 cells vacuolar proton translocating atpases protein transport extracellular fluid cytosol hydrogen ion concentration physiology matrix metalloproteinase 9 hemeproteins humans cell membrane lactic acid hrg 1 protein human neoplasm invasiveness mmp9 protein human slc2a1 protein human mmp2 protein human glucose transporter type 1 glucose metabolism matrix metalloproteinase 2

HRG-1 enhances cancer cell invasive potential and couples glucose metabolism to cytosolic/extracellular pH gradient regulation by the vacuolar-H(+) ATPase. (2013)

Abstract Haeme-responsive gene (HRG)-1 encodes a 16-kDa transmembrane protein that is induced by insulin-like growth factor-1 (IGF-1) and associates with the vacuolar-(H(+)) ATPase (V-ATPase). We previously reported that HRG-1 is essential for V-ATPase activity in endosomal acidification and receptor trafficking. Here, we show that in highly invasive and migratory cancer cell lines, HRG-1 and the V-ATPase are co-expressed at the plasma membrane, whereas in less invasive cell lines and non-transformed cells HRG-1 over-expression remains confined to intracellular compartments. Stable suppression of HRG-1 in invasive breast cancer MDA-MB-231 cells decreases extracellular pH, cell growth, migration and invasion. Ectopic expression of HRG-1 in non-invasive MCF-7 cells enhances V-ATPase activity, lowers the extracellular pH and increases the pH-dependent activity of MMP2 and MMP9 matrix metalloproteinases. HRG-1 enhances trafficking of the glucose transporter-1 (GLUT-1) with a concomitant increase in glucose uptake and lactate production. HRG-1 also promotes trafficking of the insulin-like growth factor I receptor (IGF-1R), β1-integrin and IGF-1 signalling. Taken together, our findings indicate that HRG-1 expression at the plasma membrane enhances V-ATPase activity, drives glycolytic flux and facilitates cancer cell growth, migration and invasion. Thus, HRG-1 may represent a novel target for selectively disrupting V-ATPase activity and the metastatic potential of cancer cells.
Collections Ireland -> University College Cork -> PubMed

Full list of authors on original publication

R O'Connor, V Ayllon, D Papkovsky, A Zhadanov, J O'Keeffe, F M Fogarty

Experts in our system

Robert O'Connor
Dublin City University
Total Publications: 74
Dmitri B Papkovsky
University College Cork
Total Publications: 89
Fionola Fogarty
University College Cork
Total Publications: 3