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Overexpression of glycosylphosphatidylinositol (GPI) transamidase subunits phosphatidylinositol glycan class T and/or GPI anchor attachment 1 induces tumorigenesis and contributes to invasion in human breast cancer.

Abstract
Based on the oncogenic role of phosphatidylinositol glycan (PIG) class U in human tumors, we explored the role of two additional subunits of the glycosylphosphatidylinositol (GPI) transamidase complex in human breast cancer. We found that PIG class T (PIG-T) and GPI anchor attachment 1 (GPAA1) were overexpressed in breast cancer cell lines and primary tumors. Forced expression of PIG-T and GPAA1 transformed NIH3T3 cells in vitro and increased tumorigenicity and invasion of these cells in vivo. Suppression of PIG-T expression in breast cancer cell lines led to inhibition of anchorage-independent growth. Moreover, we found that PIG-T and GPAA1 expression levels positively correlated with paxillin phosphorylation in invasive breast cancer cell lines. Furthermore, suppression of PIG-T and GPAA1 expression led to a decrease in paxillin phosphorylation with a concomitant decrease in invasion ability. These results suggest that the GPI transamidase complex is composed of a group of proto-oncogenes that individually or as a group contribute to breast cancer growth. This aberrant growth is mediated, at least partially, by phosphorylation of paxillin, contributing to invasion and progression of breast cancer.
AuthorsGuojun Wu, Zhongmin Guo, Aditi Chatterjee, Xin Huang, Ethel Rubin, Feng Wu, Elizabeth Mambo, Xiaofei Chang, Motonobu Osada, Myoung Sook Kim, Chulso Moon, Joseph A Califano, Edward A Ratovitski, Susanne M Gollin, Saraswati Sukumar, David Sidransky, Barry Trink
JournalCancer research (Cancer Res) Vol. 66 Issue 20 Pg. 9829-36 (Oct 15 2006) ISSN: 0008-5472 [Print] United States
PMID17047043 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References
  • GPAA1 protein, human
  • Glycosylphosphatidylinositols
  • Membrane Glycoproteins
  • Paxillin
  • Protein Subunits
  • Acyltransferases
  • COOH-terminal signal transamidase
Topics
  • Acyltransferases (biosynthesis, genetics)
  • Breast Neoplasms (genetics, metabolism, pathology)
  • Cell Line, Tumor
  • Cell Transformation, Neoplastic (genetics, metabolism, pathology)
  • Cloning, Molecular
  • Gene Amplification
  • Gene Dosage
  • Glycosylphosphatidylinositols (biosynthesis, genetics)
  • Humans
  • Membrane Glycoproteins (biosynthesis, genetics)
  • Neoplasm Invasiveness
  • Oncogenes
  • Paxillin (metabolism)
  • Phosphorylation
  • Protein Subunits

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