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Author Notes:

Karen Abbott, Complex Carbohydrate Research Ctr., 315 Riverbend Rd., Athens, GA 30602., Tel.: 706-542-1701; Fax: 706-542-1759; E-mail: kabbott@uga.edu

We thank Tim Abbott and Darrell Austin Marlow for technical assistance and data annotation.

Subjects:

Research Funding:

This work was supported, in whole or in part, by National Institutes of Health Grants UO1CA128454 and P41RR018502.

This work was also supported by Department of Defense Breast Cancer Concept Award BC075534 (to K. L. A.).

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Biochemistry & Molecular Biology
  • MESENCHYMAL STEM-CELLS
  • SEPTICUM ALPHA-TOXIN
  • GPI TRANSAMIDASE
  • PROSTATE-CANCER
  • DIFFERENTIATION
  • ATTACHMENT
  • EXPRESSION
  • SEQUENCES
  • CLEAVAGE
  • INVASION

Proteomic Identification of Glycosylphosphatidylinositol Anchor-dependent Membrane Proteins Elevated in Breast Carcinoma

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Journal Title:

JOURNAL OF BIOLOGICAL CHEMISTRY

Volume:

Volume 287, Number 30

Publisher:

, Pages 25230-25240

Type of Work:

Article | Final Publisher PDF

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.

Copyright information:

© 2012 by The American Society for Biochemistry and Molecular Biology, Inc.

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