TSG-6 binds via its CUB_C domain to the cell-binding domain of fibronectin and increases fibronectin matrix assembly

Кузнецова, Светлана А.; Mahoney, David J.; Martin‐Manso, Gema; Ali, Tariq; Nentwich, Hilke A.; Sipes, John M.; Zeng, Bixi; Vogel, Thomas; Day, Anthony J.; Roberts, D. A.

doi:10.1016/j.matbio.2007.10.003

Cited by 36 publications

(42 citation statements)

References 32 publications

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“…Downregulation of CSMD1 expression in MCF10A cells decreased adhesion to Matrigel and fibronectin. The stimulatory role of CSMD1 in cell-matrix adhesion is consistent with the effects of other structurally similar proteins such as neuropilin-1 (33), bone morphogenetic protein 1 and TNF-stimulating gene 6 (34,35) in this process.…”

Section: Discussionsupporting

confidence: 73%

Loss of CSMD1 expression disrupts mammary duct formation while enhancing proliferation, migration and invasion

et al. 2017

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Abstract. The CUB and sushi multiple domains 1 (CSMD1) gene maps to chromosome 8p23, a region deleted in many cancers. Loss of CSMD1 expression is associated with poor prognosis in breast cancer suggesting that it acts as a tumour suppressor in this cancer. However, the function of CSMD1 is largely unknown. Herein, we investigated CSMD1 functions in cell line models. CSMD1 expression was suppressed in MCF10A and LNCaP cells using short hairpin RNA. Functional assays were performed focusing on the 'normal' MCF10A cell line. Suppression of CSMD1 significantly increased the proliferation, cell migration and invasiveness of MCF10A cells compared to shcontrols. shCSMD1 cells also showed significantly reduced adhesion to Matrigel and fibronectin. In a three-dimensional Matrigel model of MCF10A cells, reduced CSMD1 expression resulted in the development of larger and more poorly differentiated breast acini-like structures that displayed impaired lumen formation. Loss of CSMD1 expression disrupts a model of mammary duct formation while enhancing proliferation, migration and invasion. Our data suggest that CSMD1 is involved in the suppression of a transformed phenotype. IntroductionCUB and sushi multiple domains-1 (CSMD1) is a very large gene which contains 71 exons that span over 2 Mb of genomic DNA on chromosome 8p23 (1). Multiple splice variants exist for CSMD1 and these encode proteins of varying length. The largest transcript is 14.3 kb long and this encodes a 3,565 amino acid protein (1). The full-length protein is a membrane protein with an extracellular region containing 14 CUB and 28 sushi domains, a single transmembrane domain and a short cytoplasmic domain that contains a putative tyrosine phosphorylation site. CSMD1 belongs to the CSMD gene family whose members also include the structurally similar proteins CSMD2 and CSMD3 (1-3). The function of CSMD1 is largely unknown. Although CSMD1 has been shown to inhibit C3 deposition onto the surface of cells leading to the inhibition of the classical complement pathway (4,5). The structure of CSMD1 predicts that CSMD1 is a receptor for unknown ligand(s) and is involved in signal transduction (1).CSMD1 is believed to act as a tumour suppressor based on a number of observations. CSMD1 is located on chromosome 8p23, a region that is frequently deleted in different types of cancer (1,6-10). In addition, reduced CSMD1 mRNA and protein expression has been observed in different cancers (11-17). An array comparative genomic hybridization study revealed a high rate of loss of 8p23.2 containing the CSMD1 gene in advanced prostrate cancer samples. A further small real-time PCR study identified a decrease in CSMD1 mRNA levels in higher stage prostrate cancer samples (11). Similarly reduced CSMD1 expression at the mRNA level has been identified in colorectal cancer associated with reduced patient survival (12). Furthermore, somatic mutations were detected in CSMD1 in 11% (6/54) of colorectal cancer patients along side DNA methylation and allele loss, predominantly in early onset ...

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Section: Discussionsupporting

confidence: 73%

Loss of CSMD1 expression disrupts mammary duct formation while enhancing proliferation, migration and invasion

et al. 2017

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“…7 Recently, it is reported that some type of CUB domain binds to fibronectin and modulates interaction of the other matrix components. 21 Moreover, CDCP1 interacts with a number of adhesion and matrix proteins including cadherins and syndecans. 6 It is also proposed that special subsets of integrin affect phosphorylation of CDCP1.…”

Section: Discussionmentioning

confidence: 99%

CUB-Domain-Containing Protein 1 Regulates Peritoneal Dissemination of Gastric Scirrhous Carcinoma

Uekita¹,

Tanaka²,

Takigahira³

et al. 2008

The American Journal of Pathology

102

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CUB-domain-containing protein 1 (CDCP1) is a type-I transmembrane protein that is highly expressed in colon, breast, and lung cancers. We recently revealed that CDCP1 is associated with and phosphorylated by Src family kinases and is involved in the regulation of anchorage independence of certain lung cancer cell lines. In this study, we examined whether CDCP1 is involved in the regulation of tumor progression of scirrhous gastric cancer, which is a diffusely infiltrative carcinoma with high invasion potential. Expression and phosphorylation levels of CDCP1 correlated with the invasive potential of scirrhous gastric cancers. Reduction of CDCP1 expression by siRNA suppressed migration, invasion, and anchorage independence without affecting the proliferation of highly invasive scirrhous gastric cancer cells. However, CDCP1 overexpression promoted gastric cancer cell migration with low potential of invasion. Loss of CDCP1 suppressed invasion and dissemination of cancer cells that were orthotopically implanted in the gastric wall of nude mice. Expression and phosphorylation of CDCP1 were also detected in cancer cells of surgically resected tissues of human scirrhous gastric cancer by immunohistochemical analysis. Our results suggest that CDCP1 promotes invasion and peritoneal dissemination of cancer cells through the regulation of cell migration and anchorage independence. Therefore, it is both a potential prognostic and therapeutic target in certain types of gastrointestinal cancers, and suppression of its phosphorylation might be a useful strategy for modulating cancer metastasis. (Am J Pathol

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“…Protein TSG6 is not constitutively expressed in normal adult tissue but rather in inflammatory or inflammatory-like circumstances such as ovulation (18 -20). By its link module, TSG6 can bind many substances such as glycosaminoglycan, including HA, to modulate the tissue microenvironment (21,22). Heavy chains of inter-␣-inhibitor (I␣I) and HA were shown to form covalent complexes in the knee joint with rheumatoid arthritis (23).…”

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confidence: 99%

Acute and Temporal Expression of Tumor Necrosis Factor (TNF)-α-stimulated Gene 6 Product, TSG6, in Mesenchymal Stem Cells Creates Microenvironments Required for Their Successful Transplantation into Muscle Tissue

Torihashi

Kawakubo

et al. 2015

Journal of Biological Chemistry

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Background:Transplanted MSCs cannot settle in intact muscles. Results: When MSCs release TSG6 in the intact muscle, they can settle after transplantation. TSG6 forms the SHAP-hyaluronan complex with hyaluronan and I␣I. Conclusion: TSG6, hyaluronan, and I␣I are crucial factors forming footholds for the settlement and differentiation of MSCs. Significance: TSG6, hyaluronan, and I␣I serve for improvement of regenerative medicine.

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TSG-6 binds via its CUB_C domain to the cell-binding domain of fibronectin and increases fibronectin matrix assembly

Cited by 36 publications

References 32 publications

Loss of CSMD1 expression disrupts mammary duct formation while enhancing proliferation, migration and invasion

Loss of CSMD1 expression disrupts mammary duct formation while enhancing proliferation, migration and invasion

CUB-Domain-Containing Protein 1 Regulates Peritoneal Dissemination of Gastric Scirrhous Carcinoma

Acute and Temporal Expression of Tumor Necrosis Factor (TNF)-α-stimulated Gene 6 Product, TSG6, in Mesenchymal Stem Cells Creates Microenvironments Required for Their Successful Transplantation into Muscle Tissue

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