Sperm-associated antigen 9 promotes astrocytoma cell invasion through the upregulation of podocalyxin

Abstract

Abstract. Podocalyxin (PODXL) has been found to increase the aggressive phenotype of a number of cancers, including astrocytoma. In addition, the progression of astrocytoma has been associated with sperm-associated antigen 9 (SPAG9), a recently characterized oncoprotein. In the present study, the association between SPAG9 and PODXL in human astrocytoma invasion and the underlying mechanisms were investigated for the first time, to the best of our knowledge. Overexpression and knockdown of SPAG9 were performed in SW1783 (grade III astrocytoma) and U87 (grade IV astrocytoma; glioblastoma) cells, respectively. PODXL expression at both the mRNA and the protein level, as well as the PODXL gene promoter activity, were significantly increased and decreased in parallel with the overexpression and knockdown of SPAG9 in astrocytoma cells; these effects were blocked by the selective c-Jun N-terminal kinase (JNK) inhibitor SP600125 (5 µM) and restored by the JNK agonist anisomycin (25 ng/ml), respectively. SPAG9 overexpression significantly increased cell invasion and matrix metalloproteinase-9 (MMP-9) expression in SW1783 cells, and this effect was reversed by knockdown of PODXL. In U87 cells, knockdown of SPAG9 markedly decreased cell invasion and MMP-9 expression, which was completely restored by overexpression of PODXL. In conclusion, it was demonstrated in the present study that SPAG9 upregulates PODXL expression in human astrocytoma cells at the PODXL gene promoter/transcriptional level through a JNK-dependent mechanism and that PODXL is a critical mediator of the promoting effect of SPAG9 on astrocytoma cell invasion, possibly through upregulation of MMP-9 expression. This study provides novel insights into the molecular mechanisms involved in astrocytoma invasion.

Identifications of potential therapeutic targets and drugs in angiotensin II-induced hypertension

“…It was an inhibitor of protein synthesis through blocking synthesis of peptide band and was a specific antagonist of JNK (MAPK subfamilies) with a concentration of 25 ng/mL. [ 40 , 41 ] In this study, MAPK signaling pathway was enriched in AngII-induced hypertension mice, including 20 DEGs. Similarly, AngII-induced hypertension production is possibly mediated by p38 MAPK.…”

Ten genes associated with MGMT promoter methylation predict the prognosis of patients with glioma

“…SPAG9 is overexpressed in astrocytomas and can act as a critical oncoprotein by mediating cell proliferation and invasion (37). SPAG9 contributes to the invasion of astrocytoma cells through improving the expression of podocalyxin-like via a c-Jun N-terminal kinase-dependent mechanism (38,39). WDR1 overexpression is an independent predictor of unfavorable prognosis for the patients with primary glioblastoma, indicating that WDR1 is a promising prognostic marker and a candidate therapeutic target for the disease (40).…”

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

“…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.…”