Syndecan-1 supports integrin α2β1-mediated adhesion to collagen

Vuoriluoto, Karoliina; Jokinen, Johanna; Kallio, Katja; Salmivirta, Markku; Heino, Jyrki; Ivaska, Johanna

doi:10.1016/j.yexcr.2008.07.005

Cited by 65 publications

(62 citation statements)

References 38 publications

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“…In the present study, heparin reduced the contractile capacity of the mouse embryonic fibroblasts, emphasizing the important role of HS in this context. Recently, cell surface HS chains on syndecan-1 were shown to be essential for ␣2␤1-mediated adhesion of Chinese hamster ovary cells to collagen and for ␣2␤1-mediated cell spreading and actin organization on collagen (48). One of the most prevalently expressed integrins in cultured immortalized mouse embryonic fibroblasts has previously been implicated to be ␣11␤1 (30), and this was also the case in the present study.…”

Section: Figure 7 Ext1supporting

confidence: 79%

Mutation in the Heparan Sulfate Biosynthesis Enzyme EXT1 Influences Growth Factor Signaling and Fibroblast Interactions with the Extracellular Matrix

Österholm

Barczyk

Busse

et al. 2009

Journal of Biological Chemistry

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Heparan sulfate (HS) chains bind and modulate the signaling efficiency of many ligands, including members of the fibroblast growth factor (FGF) and platelet-derived growth factor families. We previously reported the structure of HS synthesized by embryonic fibroblasts from mice with a gene trap mutation of Ext1 that encodes a glycosyltransferase involved in HS chain elongation. The gene trap mutation results in low expression of Ext1, and, as a consequence, HS chain length is substantially reduced. In the present study, Ext1 mutant and wild-type mouse embryonic fibroblasts were analyzed for the functional consequences of the Ext1 mutation for growth factor signaling and interaction with the extracellular matrix. Here, we show that the phosphorylation of ERK1/2 in response to FGF2 stimulation was markedly decreased in the Ext1 mutant fibroblasts, whereas neither PDGF-BB nor FGF10 signaling was significantly affected. Furthermore, Ext1 mutants displayed reduced ability to attach to collagen I and to contract collagen lattices, even though no differences in the expression of collagen-binding integrins were observed. Reintroduction of Ext1in the Ext1 mutant fibroblasts rescued HS chain length, FGF2 signaling, and the ability of the fibroblasts to contract collagen. These data suggest that the length of the HS chains is a critical determinant of HS-protein interactions and emphasize the essential role of EXT1 in providing specific binding sites for growth factors and extracellular matrix proteins.

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Section: Figure 7 Ext1supporting

confidence: 79%

Mutation in the Heparan Sulfate Biosynthesis Enzyme EXT1 Influences Growth Factor Signaling and Fibroblast Interactions with the Extracellular Matrix

Österholm

Barczyk

Busse

et al. 2009

Journal of Biological Chemistry

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“…Flow cytometry (Gjerdrum et al, 2010), western blot (Tuomi et al, 2009) and immunofluorescence (Vuoriluoto et al, 2008) were performed as described earlier.…”

Section: Antibodies and Stainingsmentioning

confidence: 99%

Vimentin regulates EMT induction by Slug and oncogenic H-Ras and migration by governing Axl expression in breast cancer

et al. 2010

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Epithelial-to-mesenchymal transition (EMT) is a critical event in the progression toward cancer metastasis. The intermediate filament protein vimentin is an important marker of EMT and a requisite regulator of mesenchymal cell migration. However, it is not known how vimentin functionally contributes to cancer cell invasion. Here, we report that ectopic expression of oncogenic H-Ras-V12G and Slug induces vimentin expression and migration in pre-malignant breast epithelial cells. Conversely, vimentin expression is necessary for Slug-or H-Ras-V12G-induced EMT-associated migration. Furthermore, silencing of vimentin in breast epithelial cells results in specific changes in invasiveness-related gene expression including upregulation of RAB25 (small GTPase Rab25) and downregulation of AXL (receptor tyrosine kinase Axl), PLAU (plasminogen activator, urokinase) and ITGB4 (integrin b4-subunit). Importantly, gene expression profiling analyses reveal that vimentin expression correlates positively/ negatively with these genes also in multiple breast cancer cell lines and breast cancer patient samples. Focusing on the tyrosine kinase Axl, we show that induction of vimentin by EMT is associated with upregulation of Axl expression and that Axl enhances the migratory activity of pre-malignant breast epithelial cells. Using null and knock-down cells and overexpression models, we also show that regulation of breast cancer cell migration in two-and three-dimensional matrices by vimentin is Axldependent and that Axl functionally contributes to lung extravasation of breast cancer cells in mice. In conclusion, our data show that vimentin functionally contributes to EMT and is required for induction of Axl expression. Moreover, these results provide a molecular explanation for vimentin-dependent cancer cell migration during EMT by identifying Axl as a key proximal component in this process.

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“…These findings suggest that the α 2 β 1 /syndecan-1 complex is important in regulating cell adhesion to collagen and in triggering integrin downstream signalling (Vuoriluoto et al, 2008).…”

Section: Heparan Sulphate Proteoglycans (Hspg): -Syndecanmentioning

confidence: 82%

Development of monoclonal antibodies for the identification of novel invasion associated targets in human cancer

O'sullivan¹

2008

European Journal of Cancer Supplements

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Syndecan-1 supports integrin α2β1-mediated adhesion to collagen

Cited by 65 publications

References 38 publications

Mutation in the Heparan Sulfate Biosynthesis Enzyme EXT1 Influences Growth Factor Signaling and Fibroblast Interactions with the Extracellular Matrix

Mutation in the Heparan Sulfate Biosynthesis Enzyme EXT1 Influences Growth Factor Signaling and Fibroblast Interactions with the Extracellular Matrix

Vimentin regulates EMT induction by Slug and oncogenic H-Ras and migration by governing Axl expression in breast cancer

Development of monoclonal antibodies for the identification of novel invasion associated targets in human cancer

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