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.
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.
Wu
Guojun
G
Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA.
Guo
Zhongmin
Z
Chatterjee
Aditi
A
Huang
Xin
X
Rubin
Ethel
E
Wu
Feng
F
Mambo
Elizabeth
E
Chang
Xiaofei
X
Osada
Motonobu
M
Sook Kim
Myoung
M
Moon
Chulso
C
Califano
Joseph A
JA
Ratovitski
Edward A
EA
Gollin
Susanne M
SM
Sukumar
Saraswati
S
Sidransky
David
D
Trink
Barry
B
D000217:Acyltransferases / Q000096:biosynthesis* / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D003001:Cloning, Molecular; D005784:Gene Amplification; D018628:Gene Dosage; D017261:Glycosylphosphatidylinositols / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D009361:Neoplasm Invasiveness; D009857:Oncogenes; D051419:Paxillin / Q000378:metabolism; D010766:Phosphorylation; D021122:Protein Subunits
C093316:GPAA1 protein, human; D017261:Glycosylphosphatidylinositols; D008562:Membrane Glycoproteins; D051419:Paxillin; D021122:Protein Subunits; D000217:Acyltransferases; C081007:COOH-terminal signal transamidase