EpCAM Homo-oligomerization is Not the Basis for Its Role in Cell-cell Adhesion

Overview

Journal Sci Rep

Specialty Science

Date 2018 Sep 7

PMID 30185875

Citations 26

Authors

Aljaz Gaber

Seung Joong Kim

Robyn M Kaake

Mojca Bencina

Nevan Krogan

Andrej Sali

Miha Pavsic

Brigita Lenarcic

Affiliations

Soon will be listed here.

Abstract

Cell-surface tumor marker EpCAM plays a key role in proliferation, differentiation and adhesion processes in stem and epithelial cells. It is established as a cell-cell adhesion molecule, forming intercellular interactions through homophilic association. However, the mechanism by which such interactions arise has not yet been fully elucidated. Here, we first show that EpCAM monomers do not associate into oligomers that would resemble an inter-cellular homo-oligomer, capable of mediating cell-cell adhesion, by using SAXS, XL-MS and bead aggregation assays. Second, we also show that EpCAM forms stable dimers on the surface of a cell with pre-formed cell-cell contacts using FLIM-FRET; however, no inter-cellular homo-oligomers were detectable. Thus, our study provides clear evidence that EpCAM indeed does not function as a homophilic cell adhesion molecule and therefore calls for a significant revision of its role in both normal and cancerous tissues. In the light of this, we strongly support the previously suggested name Epithelial Cell Activating Molecule instead of the Epithelial Cell Adhesion Molecule.

Citing Articles

Regulation of the Function and Expression of EpCAM.

Xiao D, Xiong M, Wang X, Lyu M, Sun H, Cui Y Biomedicines. 2024; 12(5).

PMID: 38791091 PMC: 11117676. DOI: 10.3390/biomedicines12051129.

Early-onset tufting enteropathy in HAI-2-deficient mice is independent of matriptase-mediated cleavage of EpCAM.

Szabo R, Kawaguchi M, Kataoka H, Bugge T Development. 2023; 150(17).

PMID: 37539662 PMC: 10482385. DOI: 10.1242/dev.201801.

Ex vivo expansion of circulating tumour cells (CTCs).

Mohamed B, Ward M, Bates M, Spillane C, Kelly T, Martin C Sci Rep. 2023; 13(1):3704.

PMID: 36879003 PMC: 9988863. DOI: 10.1038/s41598-023-30733-6.

Understanding the versatile roles and applications of EpCAM in cancers: from bench to bedside.

Liu Y, Wang Y, Sun S, Chen Z, Xiang S, Ding Z Exp Hematol Oncol. 2022; 11(1):97.

PMID: 36369033 PMC: 9650829. DOI: 10.1186/s40164-022-00352-4.

Dual Functionalized Shows Tumor Antigen Targeting and Cytokine Binding .

Zahirovic A, Plavec T, Berlec A Front Bioeng Biotechnol. 2022; 10:822823.

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