IMR Press / FBL / Volume 13 / Issue 13 / DOI: 10.2741/3075

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on as a courtesy and upon agreement with Frontiers in Bioscience.

Glycosylation is crucial for stability of tumour and cancer stem cell antigen EpCAM
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1 Clinical Cooperation Group Molecular Oncology, GSF-Research Center for Environment and Health, and Head and Neck Research Dept. Munich, Germany
2 Department of Otorhinolaryngology, Head and Neck Surgery, Grosshadern Medical Center, Ludwig-Maximilians-University of Munich, Marchioninistr. 15, 81377 Munich, Germany
3 Leiden Institute of Chemistry, Depts of Bioorganic Synthesis and Molecular Genetics, Leiden University, The Netherlands

*Author to whom correspondence should be addressed.

Academic Editor: Olivier Gires

Front. Biosci. (Landmark Ed) 2008, 13(13), 5195–5201;
Published: 1 May 2008
(This article belongs to the Special Issue EpCAM, the revival of a long-known tumor-associated antigen)

Epithelial cell adhesion molecule EpCAM is strongly over-expressed in a variety of carcinomas where it is involved in signalling events resulting in increased expression of target genes such as c-Myc, cyclins and others, eventually conferring cells an oncogenic phenotype. However, EpCAM is also expressed in a series of healthy epithelia, albeit generally to a far lesser extend. We have uncovered differential glycosylation of EpCAM as a means to discriminate normal from malignant tissues. EpCAM was hyperglycosylated in carcinoma tissue as compared with autologous normal epithelia. All three N-glycosylation consensus sequences within EpCAM's extracellular domain were used in human and murine cells. We show that glycosylation at asparagine198 is crucial for protein stability. Mutants of EpCAM that substitute asparagine198 for alanine showed a decreased overall expression and half-life of the molecule at the plasma membrane. This is of considerable importance with respect to EpCAM variants expressed in normal tissue, where it might reveal to be less stable and thus may have repercussions on functionality.

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