Syndecan-2 Regulates Transforming Growth Factor-β Signaling

Chen, Ligong; Klass, Carmen M.; Woods, Anne

doi:10.1074/jbc.c300430200

Cited by 113 publications

(94 citation statements)

References 41 publications

(48 reference statements)

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“…SDC2 is a significant upstream regulator of the TGF-ß signaling pathway (6), regulating signaling by acting as a co-receptor for growth factors. SDC2 facilitates signaling by forming a ternary complex with TGF-ß and its signaling receptors, TGFRI and TGFRII (7)(8)(9).…”

Section: Introductionmentioning

confidence: 99%

Prognostic significance of altered expression of SDC2 and CYR61 in esophageal squamous cell carcinoma

Huang

Di²,

Xu³

et al. 2009

Oncol Rep

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Abstract. The transforming growth factor ß (TGF-ß) signaling pathway plays an important role in growth and development, and is critically involved in the genesis and development of tumors. Syndecan-2 (SDC2) and Cysteine-rich 61 (CYR61) are important genes in this pathway and SDC2 is known to be a significant upstream regulator of TGF-ß signaling. However, the roles of SDC2 and CYR61 in the development of esophageal squamous cell carcinoma (ESCC) remain unclear. In the present study, we investigated the relationship between SDC2 and CYR61 mRNA expression levels and disease prognosis in patients with ESCC. The mRNA expression of SDC2 and CYR61 was detected by quantitative real-time RT-PCR in 77 tissue specimens. Quantitative realtime RT-PCR showed that SDC2 and CYR61 mRNA expression levels were aberrant in ESCC tissue (P<0.01) and that SDC2 mRNA expression was significantly associated with tumor size (P=0.024) in ESCC. CYR61 mRNA expression was significantly associated with regional lymph node metastasis (P=0.034) and tumor size (P=0.03). A positive correlation between SDC2 and CYR61 (r=0.770; P<0.001) mRNA expression was observed. Moreover, we observed significant associations between altered expression of SDC2/CYR61 and regional lymph node metastasis (P=0.009) and TNM stages (P=0.033). Aberrant mRNA expression of CYR61 and SDC2/CYR61 (P=0.005 and P=0.026, respectively) were significantly associated with patient survival time. The multivariate Cox regression analysis showed that SDC2 and CYR61 were independent prognostic factors for survival. Our findings suggest that SDC2 may act as an a upstream regulator of the TGF-ß signaling pathway and regulate the expression of downstream target genes. Moreover, SDC2 and CYR61 expression affect the severity of cancer, and the survival of patients with ESCC. Importantly, we report that SDC2 and CYR61 are significant, independent prognostic factors for survival in ESCC. These findings may have implications for targeted therapies in patients with ESCC.

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Section: Introductionmentioning

confidence: 99%

Prognostic significance of altered expression of SDC2 and CYR61 in esophageal squamous cell carcinoma

Huang

Di²,

Xu³

et al. 2009

Oncol Rep

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“…5,6 Research shows that CYR61 may be regarded as both a suppressor and a promoter of cancer progression and tumour invasion. 14,17 Studies have shown that CYR61 can suppress carcinogenesis in nonsmall cell lung cancer or gastric carcinoma.…”

Section: Discussionmentioning

confidence: 99%

“…5,6 CYR61 is an important gene in the transforming growth factor-b (TGF-b) signalling pathway and it can be activated by thrombospondin-1 through its interaction with latent TGF-b binding proteins. This interaction results in activation of TGF-b so that it can bind to its receptors, thus stimulating the Smad pathway.…”

Section: Introductionmentioning

confidence: 99%

Cysteine-rich, angiogenic inducer, 61 expression in patients with ovarian epithelial carcinoma

Yang

Tian

et al. 2014

J Int Med Res

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Objective: Cysteine-rich, angiogenic inducer, 61 (CYR61) is a key gene in the transforming growth factor-b signalling pathway, which is involved in the development of many tumour types. This study aimed to clarify the status and clinical significance of CYR61 expression in patients with ovarian epithelial carcinoma. Methods: Tissue from patients with ovarian epithelial carcinoma or benign ovarian tumours were investigated retrospectively for CYR61 expression at mRNA and protein levels, using reverse transcription-polymerase chain reaction and immunohistochemistry, respectively. Correlations between immunohistochemical scores and several clinicopathological parameters were investigated. Results: In 50 patients with ovarian epithelial carcinoma and 50 patients with benign ovarian tumours, CYR61 expression on mRNA and protein levels was significantly higher in ovarian epithelial carcinoma tissue than in benign ovarian tissue. CYR61 expression was associated with regional lymph node metastases and progression of clinical disease stage. There was no difference in CYR61 expression between patients aged <50 years and !50 years. Conclusions: CYR61 expression was significantly upregulated in ovarian carcinoma tissue compared with benign ovarian tumour tissue samples. Protein CYR61 levels were associated with lymph node metastases and Union for International Cancer Control stage. Protein CYR61 may be useful in targeted diagnosis and therapy, for patients with ovarian epithelial carcinoma.

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“…Moreover, syndecan-2 can bind and regulate the signaling of tumor growth factor-ß, and the binding is through the ectodomain of the core protein, with the heparan sulfate chains having only a minor role. The binding is independent of the cytoplasmic domain (42).…”

Section: Syndecans and Growth Factor Signalingmentioning

confidence: 97%

<a name="home"></a>Specific structural features of syndecans and heparan sulfate chains are needed for cell signaling

Lopes

Dietrich

Nader

2006

Braz J Med Biol Res

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The syndecans, heparan sulfate proteoglycans, are abundant molecules associated with the cell surface and extracellular matrix and consist of a protein core to which heparan sulfate chains are covalently attached. Each of the syndecan core proteins has a short cytoplasmic domain that binds cytosolic regulatory factors. The syndecans also contain highly conserved transmembrane domains and extracellular domains for which important activities are becoming known. These protein domains locate the syndecan on cell surface sites during development and tumor formation where they interact with other receptors to regulate signaling and cytoskeletal organization. The functions of cell surface heparan sulfate proteoglycan have been centered on the role of heparan sulfate chains, located on the outer side of the cell surface, in the binding of a wide array of ligands, including extracellular matrix proteins and soluble growth factors. More recently, the core proteins of the syndecan family transmembrane proteoglycans have also been shown to be involved in cell signaling through interaction with integrins and tyrosine kinase receptors.

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Syndecan-2 Regulates Transforming Growth Factor-β Signaling

Cited by 113 publications

References 41 publications

Prognostic significance of altered expression of SDC2 and CYR61 in esophageal squamous cell carcinoma

Prognostic significance of altered expression of SDC2 and CYR61 in esophageal squamous cell carcinoma

Cysteine-rich, angiogenic inducer, 61 expression in patients with ovarian epithelial carcinoma

<a name="home"></a>Specific structural features of syndecans and heparan sulfate chains are needed for cell signaling

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