N-Glycomic and Transcriptomic Changes Associated with CDX1 mRNA Expression in Colorectal Cancer Cell Lines.

Stephanie Holst,Yoann Rombouts,Jennifer Wilding,Kamila Koprowska,Manfred Wuhrer

doi:10.3390/cells8030273

Abstract

The caudal-related homeobox protein 1 (CDX1) is a transcription factor, which is important in the development, differentiation, and homeostasis of the gut. Although the involvement of CDX genes in the regulation of the expression levels of a few glycosyltransferases has been shown, associations between glycosylation phenotypes and CDX1 mRNA expression have hitherto not been well studied. Triggered by our previous study, we here characterized the N-glycomic phenotype of 16 colon cancer cell lines, selected for their differential CDX1 mRNA expression levels. We found that high CDX1 mRNA expression associated with a higher degree of multi-fucosylation on N-glycans, which is in line with our previous results and was supported by up-regulated gene expression of fucosyltransferases involved in antenna fucosylation. Interestingly, hepatocyte nuclear factors (HNF)4A and HNF1A were, among others, positively associated with high CDX1 mRNA expression and have been previously proven to regulate antenna fucosylation. Besides fucosylation, we found that high CDX1 mRNA expression in cancer cell lines also associated with low levels of sialylation and galactosylation and high levels of bisection on N-glycans. Altogether, our data highlight a possible role of CDX1 in altering the N-glycosylation of colorectal cancer cells, which is a hallmark of tumor development.

Highlights

Glycans form an important part of the outer layer of the cell and are involved in major biological processes, including cell differentiation, adhesion, and interactions with other cells, pathogens, or the extracellular matrix, as well as cellular transformations such as cancer [1,2,3]
By screening different colorectal cancer cell lines, we previously showed an association of caudal-related homeobox protein 1 (CDX1) mRNA expression with increased multi-fucosylation, which is indicative for antenna fucosylation [9]
To validate our previous results and to further explore expression profiles of associated fucosyltransfereases, we characterized the N-glycosylation of an independent set of colorectal cancer cell lines with high (8 cell lines; CDX1high ) vs. low (8 cell lines; CDX1low ) expression of CDX1 mRNA

Summary

Introduction

Glycans form an important part of the outer layer of the cell and are involved in major biological processes, including cell differentiation, adhesion, and interactions with other cells, pathogens, or the extracellular matrix, as well as cellular transformations such as cancer [1,2,3]. Glycans occur in many structural variants as modifications on proteins and lipids. T is threonine) [4] These so-called N-glycans share a common pentasaccharide core-structure and form, depending on the elongation, high-mannose type, complex-type, or hybrid-type N-glycans (Figure 1A) [4]. Changes of specific N-glycans and other glycans have been associated with several. Cells 2019, 8, 273 diseases and cancers [5,6,7] and colorectal cancer associated glycan changes have been recently reviewed by us [8].

Results

Discussion

Conclusion