Cleavage and Cell Adhesion Properties of Human Epithelial Cell Adhesion Molecule (HEPCAM)

Tsaktanis, Thanos; Kremling, Heidi; Pavšič, Miha; Stackelberg, Ricarda von; Mack, Brigitte; Fukumori, Akio; Steiner, Harald; Vielmuth, Franziska; Spindler, Volker; Huang, Zhe; Jakubowski, Jasmine; Stoecklein, Nikolas H.; Luxenburger, Elke; Lauber, Kirsten; Lenarčič, Brigita; Gires, Olivier

doi:10.1074/jbc.m115.662700

Cited by 40 publications

(84 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, the loss of EpCAM alone does not need to translate into changes in general cell adhesion when the EMT signaling is disrupted. The result is consistent with a recent report by Tsaktanis and colleagues (41) that a cleavage or knockout of EpCAM did not affect adhesion of cells population to the matrix. Our finding stresses possible distinct roles played by EpEX and EpICD.…”

Section: Discussionsupporting

confidence: 93%

EpCAM-Regulated Transcription Exerts Influences on Nanomechanical Properties of Endometrial Cancer Cells That Promote Epithelial-to-Mesenchymal Transition

et al. 2016

View full text Add to dashboard Cite

Overexpression of epithelial cell adhesion molecule (EpCAM) has been implicated in advanced endometrial cancer, but its roles in this progression remain to be elucidated. In addition to its structural role in modulating cell-surface adhesion, here we demonstrate that EpCAM is a regulatory molecule in which its internalization into the nucleus turns on a transcription program. Activation of EGF/EGFR signal transduction triggered cell-surface cleavage of EpCAM, leading to nuclear internalization of its cytoplasmic domain EpICD. ChIP-seq analysis identified target genes that are co-regulated by EpICD and its transcription partner, LEF-1. Network enrichment analysis further uncovered a group of 105 genes encoding functions for tight junction, adherent and cell migration. Furthermore, nanomechanical analysis by atomic force microscope (AFM) revealed increased softness and decreased adhesiveness of EGF-stimulated cancer cells, implicating acquisition of an epithelial-mesenchymal transition (EMT) phenotype. Thus, genome editing of EpCAM could be associated with altering these nanomechanical properties towards a less aggressive phenotype. Using this integrative genomic-biophysical approach, we demonstrate for the first time an intricate relationship between EpCAM-regulated transcription and altered biophysical properties of cells that promote EMT in advanced endometrial cancer.

show abstract

Section: Discussionsupporting

confidence: 93%

EpCAM-Regulated Transcription Exerts Influences on Nanomechanical Properties of Endometrial Cancer Cells That Promote Epithelial-to-Mesenchymal Transition

et al. 2016

View full text Add to dashboard Cite

show abstract

“…As described previously, a recent study suggested that EpCAM does not homo-oligomerize with another EpCAM on the other cell [31]. Since this oligomerization is a signature of homophilic interaction capable of mediating cell-cell adhesion activity, it is questionable to conclude that EpCAM has a direct role in homophilic adhesion molecule [31,58]. Of note, the closest homologue is TROP2, which shares 67% amino acid sequence similarity, hence one of EpCAM aliases is TROP-1 [59,60].…”

Section: Epcam Expression In Normal Tissuesmentioning

confidence: 88%

“…For example, overexpression of EpCAM has a negative effect on the strength of classical CAM's E-Cadherin-mediated cell adhesion where it weakens the property of adherens junctions [54,57]. Furthermore, CRISPR-Cas9 mediated EpCAM knockout in FaDu hypopharynx carcinoma cell line showed no notable effect on cell-matrix or cell-cell adhesion property [58]. Inhibition of cleavage activity also does not affect EpCAM cell adhesion property suggesting that EpCAM cell surface expression (EpEX) is intact upon RIP signalling.…”

Section: Epcam Expression In Normal Tissuesmentioning

confidence: 99%

Revisiting the Roles of Pro-Metastatic EpCAM in Cancer

et al. 2020

View full text Add to dashboard Cite

Epithelial cell adhesion molecule (EpCAM) is a cell surface protein that was discovered as a tumour marker of epithelial origins nearly four decades ago. EpCAM is expressed at basal levels in the basolateral membrane of normal epithelial cells. However, EpCAM expression is upregulated in solid epithelial cancers and stem cells. EpCAM can also be found in disseminated tumour cells and circulating tumour cells. Various OMICs studies have demonstrated that EpCAM plays roles in several key biological processes such as cell adhesion, migration, proliferation and differentiation. Additionally, EpCAM can be detected in the bodily fluid of cancer patients suggesting that EpCAM is a pathophysiologically relevant anti-tumour target as well as being utilized as a diagnostic/prognostic agent for a variety of cancers. This review will focus on the structure-features of EpCAM protein and discuss recent evidence on the pathological and physiological roles of EpCAM in modulating cell adhesion and signalling pathways in cancers as well as deliberating the clinical implication of EpCAM as a therapeutic target.

show abstract

“…20 ; a kind gift by Olivier Gires) which both lack endogenous EpCAM expression. Cells were cultured in DMEM supplemented with 10% FBS and 1% Pen/Strep.…”

Section: Methodsmentioning

confidence: 99%

EpCAM homo-oligomerization is not the basis for its role in cell-cell adhesion

Gaber

Kim

Kaake

et al. 2018

Sci Rep

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Cleavage and Cell Adhesion Properties of Human Epithelial Cell Adhesion Molecule (HEPCAM)

Cited by 40 publications

References 61 publications

EpCAM-Regulated Transcription Exerts Influences on Nanomechanical Properties of Endometrial Cancer Cells That Promote Epithelial-to-Mesenchymal Transition

EpCAM-Regulated Transcription Exerts Influences on Nanomechanical Properties of Endometrial Cancer Cells That Promote Epithelial-to-Mesenchymal Transition

Revisiting the Roles of Pro-Metastatic EpCAM in Cancer

EpCAM homo-oligomerization is not the basis for its role in cell-cell adhesion

Contact Info

Product

Resources

About