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Journal article
Intrinsic hepatocyte dedifferentiation is accompanied by upregulation of mesenchymal markers, protein sialylation and core alpha 1,6 linked fucosylation
Scientific reports, v 6(1), pp 27965-27965
22 Jun 2016
PMID: 27328854
Featured in Collection : UN Sustainable Development Goals @ Drexel
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 alpha-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 alpha-1,6-linked core fucosylation are observed following activation of the beta-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.
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Details
- Title
- Intrinsic hepatocyte dedifferentiation is accompanied by upregulation of mesenchymal markers, protein sialylation and core alpha 1,6 linked fucosylation
- Creators
- Anand Mehta - Drexel UniversityMary Ann Comunale - Drexel UniversitySiddhartha Rawat - Drexel UniversityJessica C. Casciano - Drexel UniversityJason Lamontagne - Drexel UniversityHarmin Herrera - Drexel UniversityAarti Ramanathan - Drexel UniversityLucy Betesh - Drexel UniversityMengjun Wang - Drexel UniversityPamela Norton - Drexel UniversityLaura F. Steel - Drexel UniversityMichael J. Bouchard - Drexel University
- Publication Details
- Scientific reports, v 6(1), pp 27965-27965
- Publisher
- Springer Nature
- Number of pages
- 14
- Grant note
- S10OD016400 / OFFICE OF THE DIRECTOR, NATIONAL INSTITUTES OF HEALTH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA R01 CA120206; U01 CA168856; F31 CA171712; F31 CA171850 / National Cancer Institute (NCI); United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) R01CA120206 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology; Microbiology and Immunology
- Web of Science ID
- WOS:000378218300001
- Scopus ID
- 2-s2.0-84975747554
- Other Identifier
- 991019168818704721
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- Web of Science research areas
- Biochemistry & Molecular Biology