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Sci Rep. 2016 Jun 22;6:27965. doi: 10.1038/srep27965.

Intrinsic hepatocyte dedifferentiation is accompanied by upregulation of mesenchymal markers, protein sialylation and core alpha 1,6 linked fucosylation.

Author information

1
Drexel University College of Medicine, Department of Microbiology and Immunology, 245 N. 15th Street, Philadelphia, PA 19102, USA.
2
Graduate School of Biomedical Sciences and Professional Studies, Drexel University College of Medicine, Molecular and Cellular Biology and Genetics Graduate Program, 245 North 15th Street, Philadelphia, PA 19102, USA.
3
Graduate School of Biomedical Sciences and Professional Studies, Drexel University College of Medicine, Microbiology and Immunology Graduate Program, 2900 Queen Lane, Philadelphia, PA 19129, USA.
4
Drexel University College of Medicine, Department of Microbiology and Immunology, Institute for Molecular Medicine and Infectious Disease, 245 North 15th Street, Philadelphia, PA 19102, USA.
5
Drexel University College of Medicine, Department of Biochemistry and Molecular Biology, 245 N. 15th Street, Philadelphia, PA 19102, USA.

Abstract

Alterations in N-linked glycosylation have long been associated with cancer but for the most part, the reasons why have remained poorly understood. Here we show that increased core fucosylation is associated with de-differentiation of primary hepatocytes and with the appearance of markers indicative of a transition of cells from an epithelial to a mesenchymal state. This increase in core fucosylation was associated with increased levels of two enzymes involved in α-1,6 linked fucosylation, GDP-mannose 4, 6-dehydratase (Gmds) and to a lesser extent fucosyltransferase 8 (Fut8). In addition, the activation of cancer-associated cellular signaling pathways in primary rat hepatocytes can increase core fucosylation and induce additional glycoform alterations on hepatocyte proteins. Specifically, we show that increased levels of protein sialylation and α-1,6-linked core fucosylation are observed following activation of the β-catenin pathway. Activation of the Akt signaling pathway or induction of hypoxia also results in increased levels of fucosylation and sialylation. We believe that this knowledge will help in the better understanding of the genetic factors associated with altered glycosylation and may allow for the development of more clinically relevant biomarkers.

PMID:
27328854
PMCID:
PMC4916422
DOI:
10.1038/srep27965
[Indexed for MEDLINE]
Free PMC Article

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