Elevated expression of C10orf3 (chromosome 10 open reading frame 3) is involved in the growth of human colon tumor

Abstract

After analysing gene-expression profiles of colon cancers on a cDNA microarray containing cDNAs corresponding to 23 040 human genes, we focused on a gene annotated as C10orf3 (chromosome 10 open reading frame 3), whose expression was elevated in colorectal cancers (CRC) as well as in tumors arising in the stomach, lung, pancreas, and breast. The gene encodes a putative 464-amino-acid protein containing a domain known as AAA (ATPases associated with a variety of cellular activities). Western blot analysis using an antibody to the gene product confirmed that the protein was overexpressed in nine of the 15 clinical cancer tissues examined, compared to corresponding noncancerous epithelial cells. A subsequent proteomics analysis revealed that C10orf3 product associated with the product of tumor susceptibility gene 101 (TSG101), and that C10orf3 downregulated TSG101 in a post-transcriptional manner. Expression of short interfering RNA in cells derived from CRC caused significant decreases in C10orf3 expression and inhibited growth of the transfected cells, which was associated with increased apoptotic cells. These data suggest that elevated C10orf3 expression might play an essential role in the growth of cancer cells, and that suppression of C10orf3-mediated signal transduction may be a novel therapeutic strategy to a wide range of human tumors.

Expression of FLJ10540 is correlated with aggressiveness of oral cavity squamous cell carcinoma by stimulating cell migration and invasion through increased FOXM1 and MMP-2 activity

“…We previously reported that FLJ10540 was overexpressed in hepatocellular carcinoma patients and it possessed a number of oncogenic characteristics, including anchorage-independent growth, enhanced cell growth at low serum levels and the induction of tumorigenesis in nude mice (Chen et al, 2007). In addition, Sakai et al (2006) also found that C10orf3 was overexpressed in clinical colon cancer tissues and it downregulated the tumor suppressor, TSG101, in a post-transcriptional manner (). Although the FLJ10540 expression is associated with cancer in humans, the causative role of FLJ10540 in tumor progression is unclear.…”

“…The application of this knowledge will lead to a better understanding of the biology of this tumor, and will provide prognostic information for defining subgroups of patients with an unfavorable prognosis as potential candidates for adjuvant or novel therapies. FLJ10540 has several names, including CEP55 (Fabbro et al, 2005), C10orf3 (Sakai et al, 2006) and URCC6. FLJ10540 is overexpressed in human colon cancer (Sakai et al, 2006), in hepatocellular carcinoma (Chen et al, 2007) and in lung cancer (Chen et al, 2009), suggesting that it may function as an oncogene in tumor development.…”

“…FLJ10540 has several names, including CEP55 (Fabbro et al, 2005), C10orf3 (Sakai et al, 2006) and URCC6. FLJ10540 is overexpressed in human colon cancer (Sakai et al, 2006), in hepatocellular carcinoma (Chen et al, 2007) and in lung cancer (Chen et al, 2009), suggesting that it may function as an oncogene in tumor development. In addition, we previously showed that the overexpression of FLJ10540 contributes to cellular transformation through the activation of PI3K/AKT (Chen et al, 2007).…”

FLJ10540-elicited cell transformation is through the activation of PI3-kinase/AKT pathway

“…In addition, at the terminal stage of cytokinesis, CEP55 is required for the midbody structure and for the completion of cytokinesis (Zhao et al, 2006). FLJ10540 is also overexpressed in colon cancer (Sakai et al, 2006). Microarray profiling of breast and lung cancers (Ma et al, 2003) also shows overexpression patterns in tumor specimens; however, no further analysis of FLJ10540 in human cancers has been reported.…”

“…FLJ10540 has several names, including CEP55 (Fabbro et al, 2005) and C10orf3 (Sakai et al, 2006). CEP55 fused with green fluorescent protein-C (GFP-C) tagged is localized at centrosome throughout mitosis (Fabbro et al, 2005).…”