Involvement of α 1‐2‐fucosyltransferase I (FUT1) and surface‐expressed lewis<sup>y</sup> (CD174) in first endothelial cell–cell contacts during angiogenesis

Michel, Thomas; Sauer, Sandra; Witzel, Maximilian; Andrulis, Mindaugas; García-Vallejo, Juan J.; Grobholz, Rainer; Willhauck‐Fleckenstein, Martina; Greiner, Andreas; Goldschmidt, Hartmut; Schwartz‐Albiez, Reinhard

doi:10.1002/jcp.21285

Cited by 41 publications

(57 citation statements)

References 23 publications

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“…6, 36). Several lines of evidence suggest that FUT1 and FUT2 play important roles in angiogenesis (37,38). Our findings of GHCer-induced angiogenesis provide yet another mechanism by which FUT1 and FUT2 contribute to increased angiogenesis.…”

Section: Discussionmentioning

confidence: 66%

“…4A, top), GHCer was detected only at the surface membrane before starting endocytosis. GHCer appeared in the cytoplasm as early as 1 minute after warming to 37 C and increased with time. On the other hand, in the presence of Filipin III, GHCer persisted on the surface membrane with very little GHCer detectable in the cytoplasm for up to 10 minutes (Fig.…”

Section: Endocytosis Of Ghcer Is Necessary For Forming Complex With Traxmentioning

confidence: 99%

“…Briefly, cells were incubated with various amount of GHCer for 5 minutes at 37 C then fixed and permeabilized, washed twice in cold PBS, and then labeled with antibodies tagged with donor (PE) or acceptor (Cy5) dyes. GHC staining was performed using unlabeled mouse antibody (mAbVK9) and a saturating amount of PE-labeled anti-mouse IgG (Biolegend).…”

Section: Fluorescence Resonance Energy Transfermentioning

confidence: 99%

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Globo-H Ceramide Shed from Cancer Cells Triggers Translin-Associated Factor X-Dependent Angiogenesis

et al. 2014

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Tumor angiogenesis is a critical element of cancer progression, and strategies for its selective blockade are still sought. Here, we examine the angiogenic effects of Globo-H ceramide (GHCer), the most prevalent glycolipid in a majority of epithelial cancers and one that acts as an immune checkpoint. Here, we report that GHCer becomes incorporated into endothelial cells through the absorption of microvesicles shed from tumor cells. In endothelial cells, GHCer addition induces migration, tube formation, and intracellular Ca 2þ mobilization in vitro and angiogenesis in vivo. Breast cancer cells expressing high levels of GHCer displayed relatively greater tumorigenicity and angiogenesis compared with cells expressing low levels of Globo-H. Clincally, GHCer þ breast cancer specimens contained higher vessel density than GHCer À breast cancer specimens. Mechanistic investigations linked the angiogenic effects of GHCer to its endocytosis and binding to TRAX, with consequent release of PLCb1 from TRAX to trigger Ca 2þ mobilization. Together, our findings highlight the importance of GHC as a target for cancer therapy by providing new information on its key role in tumor angiogenesis. Cancer Res; 74(23); 6856-66. Ó2014 AACR.

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Section: Discussionmentioning

confidence: 66%

Section: Endocytosis Of Ghcer Is Necessary For Forming Complex With Traxmentioning

confidence: 99%

Section: Fluorescence Resonance Energy Transfermentioning

confidence: 99%

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Globo-H Ceramide Shed from Cancer Cells Triggers Translin-Associated Factor X-Dependent Angiogenesis

et al. 2014

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“…Most studies have reported low survival in crc patients with high levels of α(1,2)Ft activity (5,8) or a high expression of its fucosylated products (27). However, recent studies with endothelial and tumour cell lines have demonstrated the inhibition of angiogenesis and metastatic capacity in these cells through the up-regulation of FUT1 and H 2 /le y determinant expression (17,28). the importance of sialylated le a and le x antigens in endothelial extravasation via e-selectin is well known (30).…”

Section: Discussionmentioning

confidence: 99%

α(1,2)fucosylation in human colorectal carcinoma

Muinelo-Romay

Gil‐Martín²,

Fernández-Briera³

2010

Oncology Letters

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Abstract. lewis b and lewis y (le) antigens are known to be elevated in colorectal tumours. Alterations in the catalytic behaviour of gDP-l-fucose:β-D-galactoside α(1,2) fucosyltransferase [α(1,2)Ft, ec: 2.4.1.69], the key enzyme in their synthesis, have been suggested as being responsible for these changes. In particular, an aberrant tumour-specific α(1,2)Ft activity that converts le a and le x to le b and le y determinants, respectively, has been reported in colorectal cancer tissues. to clarify the catalytic function of this enzyme during colorectal tumorigenesis, we analyzed α(1,2)Ft activity levels in healthy and tumour colon specimens using different acceptor substrates and determined the kinetic properties of the enzyme. to complete the study, the aberrant le a /le x α(1,2) fucosylation was determined in healthy and tumour colorectal tissues. A correlation analysis between the activity levels and various standard clinicopathological features, such as tumour stage, was also carried out to elucidate the role of these activities in tumour progression. The results obtained confirm the enhanced α(1,2)fucosylation in colorectal neoplastic tissues and the importance of the aberrant le a /le x α(1,2)Ft activity in this increase. However, taking into account the high levels of le a /le x fucosylation observed in healthy control tissues, we must rule out the idea of a colorectal tumour-specific α(1,2) FT. On the other hand, no significant association was observed between α(1,2)Ft activity levels and the clinicopathological characteristics. overall, our results suggest that α(1,2)Ft activity plays a critical role in the accumulation of le b and le y antigens in human colorectal carcinoma. IntroductionAlterations in glycosylation patterns are one of the characteristics associated with differentiation and malignant transformation (1). the oligosaccharide portions of cellular glycoconjugates, glycolipids and glycoproteins, convey specific immunodeterminants, such as the blood group and related antigens (2). these antigens are known to play an important role in cell recognition, interaction, adhesion and motility. Accordingly, changes in these antigens during carcinogenesis may be crucial in tumour progression and may be involved in extravasation and metastatic phenomena (3).ABo and related determinants are the result of the sequential addition of monosaccharide units to one of the five disaccharide precursors described. type 1 [galβ (1,3)glcnac β1-r] and 2 [gal β(1,4)glcnac β1-r] precursors produce H 1 and H 2 structures, respectively, after the addition of a fucose in α(1,2) linkage to the terminal β-galactosyl residue. H 1 and H 2 determinants can subsequently be converted into le b and le y difucosylated antigens by fucosylation in α(1,4) or α(1,3) linkage, respectively. their positional isomers, the le a and le x antigens, show a similar structure, but the antigens are not fucosylated in α(1,2) (4). Specific alterations of Lewis antigens have been reported in multiple carcinomas and have been correlated with the pr...

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“…DUSP5, NRARP) regulate angiogenesis ( Fig. 9H) (Al-Greene et al, 2013;Bellou et al, 2009;Herbert et al, 2012;Iaccarino et al, 2005;Mirza et al, 2013;Moehler et al, 2008;Phng et al, 2009;Pin et al, 2012;Prahst et al, 2014;Toffoli et al, 2009;Zhou et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Dynamic regulation of VEGF-inducible genes by an ERK-ERG-p300 transcriptional network

et al. 2017

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The transcriptional pathways activated downstream of vascular endothelial growth factor (VEGF) signaling during angiogenesis remain incompletely characterized. By assessing the signals responsible for induction of the Notch ligand delta-like 4 (DLL4) in endothelial cells, we find that activation of the MAPK/ERK pathway mirrors the rapid and dynamic induction of DLL4 transcription and that this pathway is required for DLL4 expression. Furthermore, VEGF/ERK signaling induces phosphorylation and activation of the ETS transcription factor ERG, a prerequisite for DLL4 induction. Transcription of DLL4 coincides with dynamic ERG-dependent recruitment of the transcriptional co-activator p300. Genome-wide gene expression profiling identified a network of VEGF-responsive and ERG-dependent genes, and ERG chromatin immunoprecipitation (ChIP)-seq revealed the presence of conserved ERG-bound putative enhancer elements near these target genes. Functional experiments performed in vitro and in vivo confirm that this network of genes requires ERK, ERG and p300 activity. Finally, genome-editing and transgenic approaches demonstrate that a highly conserved ERG-bound enhancer located upstream of HLX (which encodes a transcription factor implicated in sprouting angiogenesis) is required for its VEGFmediated induction. Collectively, these findings elucidate a novel transcriptional pathway contributing to VEGF-dependent angiogenesis.

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Involvement of α 1‐2‐fucosyltransferase I (FUT1) and surface‐expressed lewis^y (CD174) in first endothelial cell–cell contacts during angiogenesis

Cited by 41 publications

References 23 publications

Globo-H Ceramide Shed from Cancer Cells Triggers Translin-Associated Factor X-Dependent Angiogenesis

Globo-H Ceramide Shed from Cancer Cells Triggers Translin-Associated Factor X-Dependent Angiogenesis

α(1,2)fucosylation in human colorectal carcinoma

Dynamic regulation of VEGF-inducible genes by an ERK-ERG-p300 transcriptional network

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Involvement of α 1‐2‐fucosyltransferase I (FUT1) and surface‐expressed lewisy (CD174) in first endothelial cell–cell contacts during angiogenesis

Cited by 41 publications

References 23 publications

Globo-H Ceramide Shed from Cancer Cells Triggers Translin-Associated Factor X-Dependent Angiogenesis

Globo-H Ceramide Shed from Cancer Cells Triggers Translin-Associated Factor X-Dependent Angiogenesis

α(1,2)fucosylation in human colorectal carcinoma

Dynamic regulation of VEGF-inducible genes by an ERK-ERG-p300 transcriptional network

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Involvement of α 1‐2‐fucosyltransferase I (FUT1) and surface‐expressed lewis^y (CD174) in first endothelial cell–cell contacts during angiogenesis