SPAG9 expression is increased in human prostate cancer and promotes cell motility, invasion and angiogenesis in vitro

Abstract

Sperm-associated antigen 9 (SPAG9) is a recently characterized oncoprotein involved in the progression of several human malignancies. To elucidate the role of SPAG9 in the development of human prostate cancer (PCa), tissue microarray (TMA) and immunohistochemistry were used to detect the clinical relevance of SPAG9 in PCa tissues. We found that SPAG9 expression was increased in the PCa tissues when compared with the level in the tumor adjacent normal prostate tissues, and increased SPAG9 staining was significantly correlated with TNM stage and tumor grade. We also examined prostate cancer cell motility, invasion and angiogenesis ability following reduced SPAG9 expression by siRNA. Our data showed that knockdown of SPAG9 in prostate cancer cell lines inhibited cell motility and invasion due to the inactivation of metalloproteinase-2 (MMP‑2)/MMP-9 by upregulation of tissue inhibitor of metalloproteinase-1 (TIMP-1)/TIMP-2. Furthermore, downregulation of vascular endothelial growth factor (VEGF) secretion greatly contributed to the reduced ability of angiogenesis. Our data indicate that SPAG9 expression is significantly increased in PCa and it may be involved in the process of prostate cancer cell motility, migration and angiogenesis.

Transcriptomic analyses reveal tissue-specific selection on genes related to apoptotic processes in the subterranean rodent,Ctenomys sociabilis

“…Three of these genes (Sperm Associated Antigen 9; SPAG9, Cell Division Cycle 7; CDC7, and Zinc Finger CCCH-Type Containing 13; ZC3H13) have been previously characterized in humans. Upregulated in cancerous cells, SPAG9 is thought to be an early marker for diagnosis (Baser et al, 2013; Chen et al, 2014). Cell Division Cycle 7 is a DNA replication regulator, and can inactivate tumor suppressor protein p53 when CDC7 is overexpressed in tumor cells (Bonte et al, 2008; Ito et al, 2012).…”

Targeting cancer testis antigens for biomarkers and immunotherapy in colorectal cancer: Current status and challenges

“…Mechanistically, SPAG9 is involved in cellular proliferation, probably by regulating cyclin proteins as reported in hepatocellular carcinoma and prostate cancer [89][90][91] . In prostate cancer, the role of SPAG9 is not only restricted to cellular growth/proliferation but also in angiogenesis [90] . In astrocytoma and prostate cancer, SPAG9 is associated with cellular migration and invasion by modulating MMPs [88,90] .…”

“…Recently, SPAG9 serum levels were determined in endometrial cancer patients and the cut off levels of 15 ng/mL could provide the sensitivity of 74% and specificity of 83% to detect endometrial cancers [85,86] . SPAG9 expression was also found in brain cancer/astrocytoma [87,88] , prostate cancer [89,90] , hepatocellular carcinoma [91] , lung cancer [92] , vulva cancer and non skin melanoma [93] . Till date, SPAG9 is the most versatile and promising CT antigen that can be clinically translated for biomarker development and immunotherapeutic use.…”

“…In prostate cancer, the role of SPAG9 is not only restricted to cellular growth/proliferation but also in angiogenesis [90] . In astrocytoma and prostate cancer, SPAG9 is associated with cellular migration and invasion by modulating MMPs [88,90] . Table 1 summarizes the gene and protein expression of SPAG9, serological analyses of SPAG9 antigen levels and antibody responses in different cancers studied so far.…”

Direct targeting sperm-associated antigen 9 by miR-141 influences hepatocellular carcinoma cell growth and metastasis via JNK pathway

“…Several studies have reported an association of aberrant SPAG9 expressions in various types of human cancers including breast, thyroid, cervical, and colon carcinoma [ 5 – 8 ]. The down-regulation of SPAG9 by siRNA approach could also inhibit tumor cell proliferation and invasion [ 9 , 10 ]. Recently, SPAG9 overexpression was identified to be correlated with poor prognosis and tumor progression in human HCC [ 11 ].…”