Proteomic identification of glycosylphosphatidylinositol anchor-dependent membrane proteins elevated in breast carcinoma Article

Zhao, P, Nairn, AV, Hester, S et al. (2012). Proteomic identification of glycosylphosphatidylinositol anchor-dependent membrane proteins elevated in breast carcinoma . JOURNAL OF BIOLOGICAL CHEMISTRY, 287(30), 25230-25240. 10.1074/jbc.M112.339465

cited authors

  • Zhao, P; Nairn, AV; Hester, S; Moremen, KW; O'Regan, RM; Oprea, G; Wells, L; Pierce, M; Abbott, KL

authors

abstract

  • The glycosylphosphatidylinositol (GPI) anchor is a lipid and glycan modification added to the C terminus of certain proteins in the endoplasmic reticulum by the activity of a multiple sub-unit enzyme complex known as the GPI transamidase (GPIT). Several subunits of GPIT have increased expression levels in breast carcinoma. In an effort to identify GPI-anchored proteins and understand the possible role of these proteins in breast cancer progression, we employed a combination of strategies. First, alpha toxin from Clostridium septicum was used to capture GPI-anchored proteins from human breast cancer tissues, cells, and serum for proteomic analysis. We also expressed short interfering RNAs targeting the expression of the GPAA1 and PIGT subunits of GPIT in breast cancer cell lines to identify proteins in which membrane localization is dependent on GPI anchor addition. Comparative membrane proteomics using nano-ESI-RPLC- MS/MS led to the discovery of several new potential diagnostic and therapeutic targets for breast cancer. Furthermore, we provide evidence that increased levels of GPI anchor addition in malignant breast epithelial cells promotes the dedifferentiation of malignant breast epithelial cells in part by increasing the levels of cell surface markers associated with mesenchymal stem cells. © 2012 by The American Society for Biochemistry and Molecular Biology, Inc.

publication date

  • July 20, 2012

published in

Digital Object Identifier (DOI)

start page

  • 25230

end page

  • 25240

volume

  • 287

issue

  • 30