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

Guojun 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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)9829-9836
Number of pages8
JournalCancer Research
Volume66
Issue number20
DOIs
StatePublished - Oct 15 2006

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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