Profiling the expression pattern of GPI transamidase complex subunits in human cancer

Abstract

The glycosylphosphatidylinositol transamidase complex (GPIT) consists of five subunits: PIG-U, PIG-T, GPAA1, PIG-S and GPI8, and is important in attaching GPI anchors to target proteins. On the basis of our previous reports incriminating PIG-U as an oncogene in bladder cancer and PIG-T and GPAA1 as oncogenes in breast cancer, we evaluated the expression pattern of the GPIT subunits in 19 different human cancers at both mRNA and protein levels. In general, our results demonstrate a more frequent expression of GPIT subunits in cancers than in normal. Among the 19 anatomic sites compared; breast, ovary and uterus showed consistent evidence of overexpression of specific GPIT subunits. There was also overexpression of PIG-U and GPI8 in lymphoma. In addition, non-small cell lung carcinoma showed significant overexpression of the GPIT subunits as compared to small cell lung carcinoma and normal lung tissue. Also, deregulation of specific GPIT subunits was seen in various other cancers. Forced overexpression of two GPIT subunits; PIG-S and GPI8 alone or in combination induced increased proliferation and invasion of breast cancer cells. Collectively, our study defines a trend involving the deregulated expression and the functional contribution of the GPIT subunits in various cancers with potential implications in diagnosis, prognosis and therapeutic intervention.

Discovery of non-ETS gene fusions in human prostate cancer using next-generation RNA sequencing

“…PIGU protein has been found to be upregulated in prostate cancer (Nagpal et al 2008). Indeed, the fact that we see no obvious change in PIGU expression in the fusion positive case when compared to the entire data set stands in contrast to the previous fusions that we identified.…”

A single nucleotide polymorphism in the human PIGK gene associates with low PIGK expression in colorectal cancer patients

“…In an earlier study, we observed a low expression of PIGK protein in tumors compared to paired normal tissues of some CRC patients (11). We hypothesized that such low expression could be due to mutation in the coding regions of the PIGK gene.…”

“…However, the role of PIGK in tumorigenesis remains largely unknown. Recently, we reported a low expression of PIGK protein in some CRC, hepatocellular (HCC) and urothelial cell carcinoma (UCC) patients (11). We hypothesize that the altered expression of PIGK could be due to mutation in the coding regions of this gene.…”

“…The GPIT complex is composed of 5 subunits namely PIGU, PIGT, GPAA1, PIGS and PIGK (10). Among these 5 subunits, PIGK (GPI8) plays a crucial role in protein-GPI anchoring (10,11). It is well established that PIGK catalyzes the endoproteolysis and amidation steps involved in transfer of GPI to proteins (10).…”

The Protein Lipidation and Its Analysis

“…Several roles have been suggested for the GPI posttranslational modification apart from the membrane anchoring of proteins. Hence, GPI anchors may be involved in cell contact and adhesion and have a role in cellular communication, signal transduction, oncogenesis [18] and immune response [19]. Furthermore, this lipid modification has been shown to be relevant for prion disease pathogenesis and for parasites, which use the GPI anchor to increase their infectivity [15].…”