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Increase of O-glycosylated oncofetal fibronectin in high glucose-induced epithelial-mesenchymal transition of cultured human epithelial cells.
- Source :
-
PloS one [PLoS One] 2013 Apr 12; Vol. 8 (4), pp. e60471. Date of Electronic Publication: 2013 Apr 12 (Print Publication: 2013). - Publication Year :
- 2013
-
Abstract
- Growing evidences indicate that aberrant glycosylation can modulate tumor cell invasion and metastasis. The process termed "epithelial-mesenchymal transition" (EMT) provides a basic experimental model to shed light on this complex process. The EMT involves a striking decline in epithelial markers, accompanied by enhanced expression of mesenchymal markers, culminating in cell morphology change and increased cell motility. Few recent studies have established the participation glycosylation during EMT. Studies now come into knowledge brought to light the involvement of a site-specific O-glycosylation in the IIICS domain of human oncofetal fibronectin (onfFN) during the EMT process. Herein we show that high glucose induces EMT in A549 cells as demonstrated by TGF-β secretion, cell morphology changes, increased cellular motility and the emergence of mesenchymal markers. The hyperglycemic conditions increased onfFN protein levels, promoted an up regulation of mRNA levels for ppGalNAc-T6 and FN IIICS domain, which contain the hexapeptide (VTHPGY) required for onfFN biosynthesis. Glucose effect involves hexosamine (HBP) biosynthetic pathway as overexpression of glutamine: fructose-6-phosphate amidotransferase increases mesenchymal markers, onfFN levels and mRNA levels for FN IIICS domain. In summary, our results demonstrate, for the first time that the metabolism of glucose through HBP promotes O-glycosylation of the oncofetal form of FN during EMT modulating tumorogenesis.
- Subjects :
- Amino Acid Sequence
Biomarkers metabolism
Cell Line, Tumor
Cell Movement drug effects
Cell Shape drug effects
Epithelial Cells drug effects
Glycosylation drug effects
Hexosamines biosynthesis
Humans
Hyperglycemia pathology
Mesoderm drug effects
Mesoderm metabolism
Molecular Sequence Data
Nitrogenous Group Transferases metabolism
Peptides chemistry
Peptides pharmacology
Transforming Growth Factor beta1 pharmacology
Epithelial Cells metabolism
Epithelial-Mesenchymal Transition drug effects
Fibronectins metabolism
Glucose pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 8
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 23593224
- Full Text :
- https://doi.org/10.1371/journal.pone.0060471