CDX2 homeoprotein is involved in the regulation of ST6GalNAc-I gene in intestinal metaplasia

Pinto, Rita; Barros, Rita; Pereira-Castro, Isabel; Mesquita, Patrı́cia; Bennett, Eric; Almeida, Raquel; David, Leonor

doi:10.1038/labinvest.2015.52

Cited by 14 publications

(13 citation statements)

References 43 publications

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“…Interestingly, when we looked more in general for proteins that were different between the high binding cell lines (HT29 and HCT116) and the low MGL-binding cell line (LS174T), we observed the cluster of mucins ( Figure S4 ) in close proximity to the transcription factor CDX-2. Together with CDX-1, this protein acts as a transcription factor that in cooperation with HNF4A and 1A, is involved in the regulation of multiple intestinal specific genes [ 26 ], as well as fucosyltransferases [ 27 ] and α2,6-sialyltransferase [ 28 ]. CDX-1 is very similar to CDX-2, and these proteins share several tryptic peptides, but we did not observe a unique CDX-1 peptide in our dataset.…”

Section: Resultsmentioning

confidence: 99%

N-Glycoproteins Have a Major Role in MGL Binding to Colorectal Cancer Cell Lines: Associations with Overall Proteome Diversity

Pirro

Mohammed

Vliet

et al. 2020

IJMS

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Colorectal cancer (CRC) is the second-leading cause of cancer death worldwide due in part to a high proportion of patients diagnosed at advanced stages of the disease. For this reason, many efforts have been made towards new approaches for early detection and prognosis. Cancer-associated aberrant glycosylation, especially the Tn and STn antigens, can be detected using the macrophage galactose-type C-type lectin (MGL/CLEC10A/CD301), which has been shown to be a promising tool for CRC prognosis. We had recently identified the major MGL-binding glycoproteins in two high-MGL-binding CRC cells lines, HCT116 and HT29. However, we failed to detect the presence of O-linked Tn and STn glycans on most CRC glycoproteins recognized by MGL. We therefore investigated here the impact of N-linked and O-linked glycans carried by these proteins for the binding to MGL. In addition, we performed quantitative proteomics to study the major differences in proteins involved in glycosylation in these cells. Our results showed that N-glycans have a significant, previously underestimated, importance in MGL binding to CRC cell lines. Finally, we highlighted both common and cell-specific processes associated with a high-MGL-binding phenotype, such as differential levels of enzymes involved in protein glycosylation, and a transcriptional factor (CDX-2) involved in their regulation.

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Section: Resultsmentioning

confidence: 99%

N-Glycoproteins Have a Major Role in MGL Binding to Colorectal Cancer Cell Lines: Associations with Overall Proteome Diversity

Pirro

Mohammed

Vliet

et al. 2020

IJMS

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“…Another group studied the gastric cancer cell line MKN45, which expresses very high levels of ST6GalNAc-I and, consequently, higher sialyl-Tn levels. In this cell line, loss of ST6GalNAc-I resulted in reduced proliferation, migration, invasion, and reduced STAT5b phosphorylation and IGF-1 expression [66,67]. Ozaki et al reported increased peritoneal metastasis of sialyl-Tn-expressing gastric carcinoma cell lines when transplanted into nude mice [68].…”

Section: St6galnac-i Dependent Mucin Glycosylation In Gastric Cancermentioning

confidence: 96%

A Systematic Review on the Implications of O-linked Glycan Branching and Truncating Enzymes on Cancer Progression and Metastasis

Gupta

Leon

Rauth

et al. 2020

Cells

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Glycosylation is the most commonly occurring post-translational modifications, and is believed to modify over 50% of all proteins. The process of glycan modification is directed by different glycosyltransferases, depending on the cell in which it is expressed. These small carbohydrate molecules consist of multiple glycan families that facilitate cell–cell interactions, protein interactions, and downstream signaling. An alteration of several types of O-glycan core structures have been implicated in multiple cancers, largely due to differential glycosyltransferase expression or activity. Consequently, aberrant O-linked glycosylation has been extensively demonstrated to affect biological function and protein integrity that directly result in cancer growth and progression of several diseases. Herein, we provide a comprehensive review of several initiating enzymes involved in the synthesis of O-linked glycosylation that significantly contribute to a number of different cancers.

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“…ST6GalNAc-I has been also identified to be overexpressed in IM and its detection co-localizes, at the cellular level, with STn expression, being restricted to the perinuclear region [ 85 ]. The CDX2 homeobox transcriptor factor, normally expressed in intestinal cells, has been shown to regulate ST6GALNAC1 gene leading to the overexpression of STn [ 86 ].…”

Section: O- Glycosylation Alterations During Gamentioning

confidence: 99%

Mucin-Type O-Glycosylation in Gastric Carcinogenesis

et al. 2016

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Mucin-type O-glycosylation plays a crucial role in several physiological and pathological processes of the gastric tissue. Modifications in enzymes responsible for key glycosylation steps and the consequent abnormal biosynthesis and expression of their glycan products constitute well-established molecular hallmarks of disease state. This review addresses the major role played by mucins and associated O-glycan structures in Helicobacter pylori adhesion to the gastric mucosa and the subsequent establishment of a chronic infection, with concomitant drastic alterations of the gastric epithelium glycophenotype. Furthermore, alterations of mucin expression pattern and glycan signatures occurring in preneoplastic lesions and in gastric carcinoma are also described, as well as their impact throughout the gastric carcinogenesis cascade and in cancer progression. Altogether, mucin-type O-glycosylation alterations may represent promising biomarkers with potential screening and prognostic applications, as well as predictors of cancer patients’ response to therapy.

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CDX2 homeoprotein is involved in the regulation of ST6GalNAc-I gene in intestinal metaplasia

Cited by 14 publications

References 43 publications

N-Glycoproteins Have a Major Role in MGL Binding to Colorectal Cancer Cell Lines: Associations with Overall Proteome Diversity

N-Glycoproteins Have a Major Role in MGL Binding to Colorectal Cancer Cell Lines: Associations with Overall Proteome Diversity

A Systematic Review on the Implications of O-linked Glycan Branching and Truncating Enzymes on Cancer Progression and Metastasis

Mucin-Type O-Glycosylation in Gastric Carcinogenesis

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