Syndecan-1 is required for Wnt-1-induced mammary tumorigenesis in mice

Alexander, Caroline M.; Reichsman, Frieda; Hinkes, Michael T.; Lincecum, John; Becker, Klaus; Cumberledge, Susan; Bernfield, Merton

doi:10.1038/77108

Cited by 326 publications

(272 citation statements)

References 30 publications

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“…Thus, the reducing end residue (residue 4) of the tetrasaccharide is a 2-O-sulfated ⌬ 4,5 -uronic acid, provided that HS glycuronate-2-sulfatase specifically reacts with this residue (24). 5 Taken together, these results demonstrate that fraction D contains a tetrasaccharide with a structure of ⌬UA2S-GlcNS- 4 Two minor [ 35 S]peaks were also observed, representing [ 35 S]sulfate and IdoUA2S-AnMan3S, respectively. The IdoUA2S-AnMan3S is probably the partial desulfated IdoUA2S-AnMan3S6S because of nitrous acid degradation or the product of the minor contaminants in the fraction D. 5 It should be noted that we identified the positions of five sulfate groups in the reducing end tetrasaccharide to this end.…”

Section: Structural Characterization Of Fraction D Analysis Of Fractisupporting

confidence: 54%

“…5). 4 The result suggests that the 3-O- 35 S-sulfation site is present in a disaccharide with a structure of -IdoUA2S-GlcNH 2 3S6S-, provided that a previous report (11) demonstrated that 3-OST-3A sulfates an N-unsubstituted glucosamine residue.…”

Section: Structural Characterization Of Fraction D Analysis Of Fractimentioning

confidence: 68%

“…HS play critical roles in a variety of biological interactions, including assisting viral infection, regulating blood coagulation and embryonic development, suppressing tumor growth, and controlling the eating behavior of mice by interacting with specific regulatory proteins (1)(2)(3)(4)(5). HS is initially synthesized as a copolymer of glucuronic acid and N-acetylated glucosamine by D-glucuronyl and N-acetyl-D-glucosaminyl transferase, followed by various modifications (6).…”

Section: -O-sulfotransferase Isoform 3 (3-ost-3) and It Provides Bimentioning

confidence: 99%

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Characterization of a Heparan Sulfate Octasaccharide That Binds to Herpes Simplex Virus Type 1 Glycoprotein D

Liu

Shriver

Pope

et al. 2002

Journal of Biological Chemistry

153

116

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Herpes simplex virus type 1 utilizes cell surface heparan sulfate as receptors to infect target cells. The unique heparan sulfate saccharide sequence offers the binding site for viral envelope proteins and plays critical roles in assisting viral infections. A specific 3-O-sulfated heparan sulfate is known to facilitate the entry of herpes simplex virus 1 into cells. The 3-O-sulfated heparan sulfate is generated by the heparan sulfate D-glucosaminyl-3-O-sulfotransferase isoform 3 (3-OST-3), and it provides binding sites for viral glycoprotein D (gD). Here, we report the purification and structural characterization of an oligosaccharide that binds to gD. The isolated gDbinding site is an octasaccharide, and has a binding affinity to gD around 18 M, as determined by affinity coelectrophoresis. The octasaccharide was prepared and purified from a heparan sulfate oligosaccharide library that was modified by purified 3-OST-3 enzyme. The molecular mass of the isolated octasaccharide was determined using both nanoelectrospray ionization mass spectrometry and matrix-assisted laser desorption/ionization mass spectrometry. The results from the sequence analysis suggest that the structure of the octasaccharide is a heptasulfated octasaccharide. The proposed structure of the octasaccharide is ⌬UA-GlcNSIdoUA2S-GlcNAc-UA2S-GlcNS-IdoUA2S-GlcNH 2 3S6S. Given that the binding of 3-O-sulfated heparan sulfate to gD can mediate viral entry, our results provide structural information about heparan sulfate-assisted viral entry.Heparan sulfates (HS), 1 highly sulfated polysaccharides, are present on the surface of mammalian cells and in the extracellular matrix in large quantities. HS play critical roles in a variety of biological interactions, including assisting viral infection, regulating blood coagulation and embryonic development, suppressing tumor growth, and controlling the eating behavior of mice by interacting with specific regulatory proteins (1-5). HS is initially synthesized as a copolymer of glucuronic acid and N-acetylated glucosamine by D-glucuronyl and N-acetyl-D-glucosaminyl transferase, followed by various modifications (6). These modifications include C 5 -epimerization of glucuronic acid to form iduronic acid residues, 2-O-sulfation of iduronic and glucuronic acid, N-deacetylation and N-sulfation of glucosamine, as well as 6-O-sulfation and 3-O-sulfation of glucosamine. Numerous HS biosynthetic enzymes have been cloned and characterized (for review, see Esko and Lindahl (7)).The specific sulfated saccharide sequences play critical roles in determining the functions of HS. A recent report suggests that the expression levels of various isoforms of each class of HS biosynthetic enzyme contribute to the synthesis of specific saccharide sequences in specific tissues (8). HS N-deacetylase/ N-sulfotransferase, 3-O-sulfotransferase, and 6-O-sulfotransferase are present in multiple isoforms, and each isoform is believed to recognize the saccharide sequence around the modification site to generate a specific sulfated saccharid...

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Section: Structural Characterization Of Fraction D Analysis Of Fractisupporting

confidence: 54%

Section: Structural Characterization Of Fraction D Analysis Of Fractimentioning

confidence: 68%

Section: -O-sulfotransferase Isoform 3 (3-ost-3) and It Provides Bimentioning

confidence: 99%

See 1 more Smart Citation

Characterization of a Heparan Sulfate Octasaccharide That Binds to Herpes Simplex Virus Type 1 Glycoprotein D

Liu

Shriver

Pope

et al. 2002

Journal of Biological Chemistry

153

116

View full text Add to dashboard Cite

show abstract

“…In this regard, several different proteoglycans and/or their glycosaminoglycan chain components that are abundantly present at the cell surface have been reported to stimulate the Wnt/β-catenin pathway. These include free heparan sulfate (4), heparin chains (5-7), and heparan sulfate proteoglycans, such as glypican-3 (8) and syndecan-1 (9).…”

mentioning

confidence: 99%

Modulation of canonical Wnt signaling by the extracellular matrix component biglycan

Berendsen

Fisher

Kilts

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

135

136

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Although extracellular control of canonical Wnt signaling is crucial for tissue homeostasis, the role of the extracellular microenvironment in modulating this signaling pathway is largely unknown. In the present study, we show that a member of the small leucine-rich proteoglycan family, biglycan, enhances canonical Wnt signaling by mediating Wnt function via its core protein. Immunoprecipitation analysis revealed that biglycan interacts with both the canonical Wnt ligand Wnt3a and the Wnt coreceptor low-density lipoprotein receptor-related protein 6 (LRP6), possibly via the formation of a trimeric complex. Biglycan-deficient cells treated with exogenous Wnt3a had less Wnt3a retained in cell layers compared with WT cells. Furthermore, the Wnt-induced levels of LRP6 phosphorylation and expression of several Wnt target genes were blunted in biglycan-deficient cells. Both recombinant biglycan proteoglycan and biglycan core protein increased Wnt-induced β-catenin/T cell-specific factor–mediated transcriptional activity, and this activity was completely inhibited by Dickkopf 1. Interestingly, recombinant biglycan was able to rescue impaired Wnt signaling caused by a previously described missense mutation in the extracellular domain of human LRP6 (R611C). Furthermore, biglycan's modulation of canonical Wnt signaling affected the functional activities of osteoprogenitor cells, including the RUNX2-mediated transcriptional activity and calcium deposition. Use of a transplant system and a fracture healing model revealed that expression of Wnt-induced secreted protein 1 was decreased in bone formed by biglycan-deficient cells, further suggesting reduced Wnt signaling in vivo. We propose that biglycan may serve as a reservoir for Wnt in the pericellular space and modulate Wnt availability for activation of the canonical Wnt pathway.

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“…It has been suggested that syndecan-1 is involved in Wnt-1 induced tumor in the mouse mammary gland (Alexander et al, 2000). It has been found that syndecan-1 promotes the metastases in lung squamous carcinoma cells (Hirabayashi et al, 1998).…”

Section: Soluble Syndecans and Tumormentioning

confidence: 99%

Syndecan as a Messenger to Link Diabetes and Cancer

Kim

Raman²

2011

Biomolecules and Therapeutics

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Cell surface syndecans are membrane-anchored proteoglycans. These glycoproteins have covalently linked glycosaminoglycan side chains. They interact via their extracellular part with various growth factors, extracellular matrix components, other cell surface molecules, and proteins involved in the regulation of blood coagulation. Thus the syndecans involve in synchronized expression patterns during embryogenesis and malignant transformation. These cell-cell interactions via their extracellular matrix ligands control cell proliferation, dynamic cytoskeletal remodeling, apoptosis and gene expression.Over the last few years, it has been widely accepted that heparan sulfate proteoglycans play a role in growth control, cell spreading, cellular recognition, cellular adhesion, and signaling, possibly as co -receptors with integrins, IGF-1R and cell -cell adhesion molecules, including fi bronectin, vitronectin, laminins, and the fi brillar collagens (Bernfi eld et al., 1999;Woods, 2001;Alexopoulou et al., 2007;Beauvais and Rapraeger, 2010). In addition, all syndecans have dibasic peptide sequence adjacent to the plasma membrane. Thus, the extracellular domains of syndecans could be cleaved by extracellular proteases. Syndecan's ectodomains have been shown to regulate a multitude of biological functions in celldependent and cell-independent approaches (Li et al., 2002;Endo et al., 2003;Elenius et al., 2004). Soluble syndecans also convert the membrane-bound receptors into soluble effectors/or antagonists. The soluble ectodomains of syndecans can compete with intact syndecans for extracellular ligands (Steinfeld et al., 1996). In this review, we will discuss the general Syndecans are membrane-anchored proteoglycans and implicated in the pathogenesis of cancer progression and metastasis. Syndecans also play important roles in interacting with growth factors, extracellular matrix and other cell surface molecules such as IGF-1 receptor. In the present review, we discuss about the syndecan structure, their role in signaling with other receptors, in addition to its general biology. The emerging roles of syndecans in the pathophysiology of human diseases, especially insulin resistance, diabetes and cancer is discussed. Abstractfeatures and their conventional roles in signaling with co-receptors. Finally, we will explore the emerging roles of syndecans in the pathophysiology of human diseases, especially type 2 diabetes. SYNDECAN STRUCTUREAll the syndecans are a type 1 transmembrane proteins that are expressed in almost every cell of the body. Four members of syndecan family have been identifi ed in mammalians such as syndecan-1, 2, 3, and 4. Syndecan-1 analogs are also identifi ed in other mammals such as mouse, rat, dog, chimpanzee, guinea pig, Chinese hamster, cat and chicken. The extracellular domains of human and mouse syndecan-1 display approximately 70% sequence homology whereas the transmembrane domain and cytoplasmic domain show 96 % and 100% sequence homology, respectively. Synthesis of four syndecan core proteins are ...

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Syndecan-1 is required for Wnt-1-induced mammary tumorigenesis in mice

Cited by 326 publications

References 30 publications

Characterization of a Heparan Sulfate Octasaccharide That Binds to Herpes Simplex Virus Type 1 Glycoprotein D

Characterization of a Heparan Sulfate Octasaccharide That Binds to Herpes Simplex Virus Type 1 Glycoprotein D

Modulation of canonical Wnt signaling by the extracellular matrix component biglycan

Syndecan as a Messenger to Link Diabetes and Cancer

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