SRPX2 is a novel chondroitin sulfate proteoglycan that is overexpressed in gastrointestinal cancer.

Department of Genome Biology, Kinki University School of Medicine, Osaka-Sayama, Osaka, Japan.
PLoS ONE (Impact Factor: 3.53). 01/2012; 7(1):e27922. DOI: 10.1371/journal.pone.0027922
Source: PubMed

ABSTRACT SRPX2 (Sushi repeat-containing protein, X-linked 2) has recently emerged as a multifunctional protein that is involved in seizure disorders, angiogenesis and cellular adhesion. Here, we analyzed this protein biochemically. SRPX2 protein was secreted with a highly posttranslational modification. Chondroitinase ABC treatment completely decreased the molecular mass of purified SRPX2 protein to its predicted size, whereas heparitinase, keratanase and hyaluroinidase did not. Secreted SRPX2 protein was also detected using an anti-chondroitin sulfate antibody. These results indicate that SRPX2 is a novel chondroitin sulfate proteoglycan (CSPG). Furthermore, a binding assay revealed that hepatocyte growth factor dose-dependently binds to SRPX2 protein, and a ligand-glycosaminoglycans interaction was speculated to be likely in proteoglycans. Regarding its molecular architecture, SRPX2 has sushi repeat modules similar to four other CSPGs/lecticans; however, the molecular architecture of SRPX2 seems to be quite different from that of the lecticans. Taken together, we found that SRPX2 is a novel CSPG that is overexpressed in gastrointestinal cancer cells. Our findings provide key glycobiological insight into SRPX2 in cancer cells and demonstrate that SRPX2 is a new member of the cancer-related proteoglycan family.

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    ABSTRACT: Altered development of the human cerebral cortex can cause severe malformations with often intractable focal epileptic seizures and may participate in common pathologies, notably epilepsy. This raises important conceptual and therapeutic issues. Two missense mutations in the sushi repeat-containing protein SRPX2 had been previously identified in epileptic disorders with or without structural developmental alteration of the speech cortex. In the present study, we aimed to decipher the precise developmental role of SRPX2, to have a better knowledge on the consequences of its mutations, and to start addressing therapeutic issues through the design of an appropriate animal model. Using an in utero Srpx2 silencing approach, we show that SRPX2 influences neuronal migration in the developing rat cerebral cortex. Wild-type, but not the mutant human SRPX2 proteins, rescued the neuronal migration phenotype caused by Srpx2 silencing in utero, and increased alpha-tubulin acetylation. Following in utero Srpx2 silencing, spontaneous epileptiform activity was recorded post-natally. The neuronal migration defects and the post-natal epileptic consequences were prevented early in embryos by maternal administration of tubulin deacetylase inhibitor tubacin. Hence epileptiform manifestations of developmental origin could be prevented in utero, using a transient and drug-based therapeutic protocol.
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    ABSTRACT: Background and Objectives Sushi repeat-containing protein X-linked 2 (SRPX2) was first described as a downstream target gene for E2A-HLA, which causes pro-B acute leukemia. SRPX2 is considered to promote cellular migration and adhesion in cancers. Our objective was to evaluate the relative expression of the SRPX2 gene and to determine whether such expression correlates with outcomes in patients with gastric cancer.Methods Surgical specimens of cancer tissue and adjacent normal mucosa obtained from 227 patients with previously untreated gastric cancer were examined. SRPX2 mRNA expression levels of cancer tissue and adjacent normal mucosa were measured by quantitative real-time polymerase chain reaction. We evaluated the clinicopathological significance of the relative expression of SRPX2 in patients with gastric cancer.ResultsSRPX2 expression was higher in cancer tissue than in adjacent normal mucosa (P < 0.001). On analysis of the relations between gene expression and clinicopathological factors, SRPX2 expression correlated with tumor size and distant metastasis. Overall survival was significantly lower in patients whose tumors had high SRPX2 expression than in those who had low SRPX2 expression (P = 0.003). Multivariate analysis showed that high SRPX2 expression was an independent predictor of survival (HR = 2.028, 95% CI = 1.265–3.251).ConclusionsSRPX2 expression was significantly higher in gastric cancer tissue than in adjacent normal mucosa, and overexpression of the SRPX2 gene is considered a useful independent predictor of outcomes in patients with gastric cancer. J. Surg. Oncol. © 2014 Wiley Periodicals, Inc.
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