Title : Glycosylation is crucial for stability of tumour and cancer stem cell antigen
EpCAM
Abstract :
- 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