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PMID: 25972125 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Glycosyltransferases involved in the synthesis of MUC-associated metastasis-promoting selectin ligands.

Glycobiology ·Vol. 25 ·No. 9 ·2015-09-00 ·Pages 963-75

Chachadi VB, Bhat G, Cheng PW

Abstract

The sialyl Lewis a and x (sLe(a/x)) antigens frequently displayed on the surface of tumor cells are involved in metastasis. Their synthesis has been attributed to altered expression of selective glycosyltransferases. Identification of these glycosyltransferases and the glycoproteins that carry these carbohydrate antigens should help advance our understanding of selectin-mediated cancer metastasis. In this study, quantitative real-time polymerase chain reaction analysis coupled with in situ proximity ligation assay and small interference RNA treatment shows involvement of β3galactosyltransferase-V in the synthesis of MUC16-associated sLe(a) in H292 cells. Also, α3fucosyltransferase-V, which is absent in BEAS-2B human immortalized bronchial epithelial cells and A549 lung carcinoma cells, participates in the synthesis of MUC1-associated sLe(x) in CFT1 human immortalized bronchial epithelial cells and H292 lung carcinoma cells. Neither selectin ligand is found on MUC1 in BEAS-2B and A549 cells. Knockdown of either enzyme suppresses migration, and selectin tethering and rolling properties of H292 cells under dynamic flow as determined by wound healing and parallel plate flow chamber assays, respectively. These results provide insights into how the synthesis of mucin-associated selectin ligands and the metastatic properties of cancer cells can be regulated by selective glycosyltransferases that work on mucins. They may help develop novel anticancer drugs.

Keywords
cell adhesion glycosylation glycosyltransferases lung cancer metastasis sialyl Lewis antigens
MeSH Terms
CA-19-9 Antigen Cell Adhesion Cell Line, Tumor Cell Movement Epithelial Cells/metabolism,physiology Galactosyltransferases/metabolism Humans Membrane Glycoproteins/genetics,metabolism Mucins/metabolism Oligosaccharides/metabolism Sialyl Lewis X Antigen
Chemicals
CA-19-9 Antigen Membrane Glycoproteins Mucins Oligosaccharides P-selectin ligand protein Sialyl Lewis X Antigen Galactosyltransferases beta-1,4-galactosyltransferase V
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Chachadi Vishwanath B
Department of Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE, USA Department of Biochemistry and Molecular Biology, College of Medicine.
Bhat Ganapati
Department of Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE, USA Department of Biochemistry and Molecular Biology, College of Medicine.
Cheng Pi-Wan
Department of Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE, USA Department of Biochemistry and Molecular Biology, College of Medicine Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, 985870 Nebraska Medical Center, Omaha, NE 68198-5870, USA pcheng@unmc.edu.
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Article Info
Journal
Glycobiology
Abbr.
Glycobiology
ISSN
1460-2423
DOI
10.1093/glycob/cwv030
Email
pcheng@unmc.edu
Published
2015-09-00
Epub
2015-00-13
Pages
963-75
Language
English
Region
England
NLM ID
9104124
PMCID
PMC4518684
Subset
IM
Grants
NHLBI NIH HHS · 2R01HL48282 · United States
External Links
PubMed source DOI: 10.1093/glycob/cwv030 PMC Full Text View journal details
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