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FLASH GENE

Symbol

EPCAM

contributors: mct/npt/pgu - updated : 21-06-2023

HGNC name	epithelial cell adhesion molecule
HGNC id	11529

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive intestine large intestine colon   highly Homo sapiens   intestine small intestine     highly Mus musculus Fetal   stomach       highly Skin/Tegument skin       highly Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Epithelial absorptive excretory digestive epithelium (mucosa)   highly Mus musculus Fetal

cells

System Cell Pubmed Species Stage Rna symbol Digestive epithelial cell Mus musculus Fetal not specific epidermal dendritic cell Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

pregnancy

Text	placenta
	highly expressed in embryonic stem cells (ESCs)

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a thyroglobulin type 1 repeat
	two epidermal growth factor-like extracellular domains
	one single transmembrane domain
	and one small intercellular domain (EpICD), that alone is sufficient to induce proliferation signals
	PDZ-domain identified in its C-terminal end

conjugated

GlycoP

isoforms

Precursor

N-terminal signal peptide is cleaved off during processing of EpCAM in both microsomes and human cells, and that 35 kDa is the normal size of non-glycosylated EPCAM

HOMOLOGY

intraspecies

homolog to TACSTD2

Homologene

FAMILY

EPCAM family

CATEGORY

adhesion , antigen

SUBCELLULAR LOCALIZATION	extracellular
	plasma membrane,junction,tight
	intracellular
	intracellular,cytoplasm,organelle
	intracellular,cytoplasm,cytosolic,microsome
text	CLDN7 colocalized with EPCAM at cell-cell junctions, and the two proteins were found to associate with each other
	type I integral membrane protein
	non-glycosylated, cleaved form of EPCAM in the microsomes

basic FUNCTION	playing a central role in cell adhesion function
	carcinoma associated antigen
	having a direct impact on cell cycle and proliferation, and the ability to rapidly upregulate the proto-oncogene c-myc and cyclin A/E
	having an oncogenic potential and activated by release of its intracellular domain, which can signal into the cell nucleus by engagement of elements of the wnt pathway
	functions partly via homotypic protein interactions mediating cell-to-cell adhesion of epithelial cells
	regulates morphogenetic movements through intracellular signaling
	EPCAM and its associated protein, CLDN7, play a critical role in reprogramming
	not merely a passenger gene that is up-regulated during reprogramming but a main player in a positive feedback loop among key factors that propel the reprogramming machinery
	enhances cell cycle progression via the classical cyclin-regulated pathway
	is an important regulator of movement of epithelial cells of distinct lineages with respect to each other
	is a negative regulator of adhesion between epithelial cells
	contributes to formation of intestinal barrier by recruiting claudins to cell-cell junctions
	involved in numerous cellular processes including cell adhesion, proliferation, maintenance of stemness of embryonic cells and progenitors, migration and invasion
	epithelial and cancer cell protein
	regulates the composition and function of tight junctions
	modulates adhesion and TJ function by regulating intracellular localization and degradation of selected claudins
	EPCAM acts likely as a prosurvival factor counteracting terminal differentiation processes in normal mammary glands
	EPCAM can act as an oncogene still depending on additional driver mutations and epithelial phenotype of tumor cells
	EPCAM plays a key role in proliferation, differentiation and adhesion processes in stem and epithelial cells
	important positive regulator of cell adhesion and migration, playing an essential role in embryonic morphogenesis as well as intestinal homeostasis
	EPCAM plays multiple important roles, in cell proliferation as well as in cell adhesion and migration
	essential for maintaining the homeostasis of the intestinal epithelium
	forms intercellular, homophilic adhesions, modulates epithelial junctional protein complex formation, and promotes epithelial tissue homeostasis
	overlapping functions of EPCAM and TACSTD2 as regulators of epithelial development in both intestinal and extraintestinal tissues

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component	protein constituent of membrane
	an EPCAM-CLDN7 complex, rather than EPCAM itself, can promote proliferation, apoptosis resistance, migration, and tumorigenicity

INTERACTION

DNA

RNA

small molecule

protein	MMP7 is a direct SOX18 target gene as well as other potential candidates including guidance molecules, suggesting a function of this transcription factor in the regulation of vessel formation
	MMP7 is a target gene of EPCAM signalling via EpICD nuclear translocation
	interact directly with the TJ protein claudin -7 (CLDN7 was required for association of CLDN1 with EPCAM)
	association between ERAP2 and EPCAM is a unique and novel finding that provides new ideas on EPCAM processing and on how antigen presentation may be regulated in cancer
	TACSTD2 was able to compensate for the loss of EPCAM in stabilizing CLDN7 expression and cell membrane localization in tissues that co-express both proteins
	cytosolic EPCAM cooperates with HRAS to regulate epithelial to mesenchymal transition through ZEB1

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

HNPCC1 , DIAR5

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   in esophageal carcinoma, with long survival tumoral     --over   in retinoblastoma tumoral     --over   in colorectal and lung carcinomas tumoral germinal mutation deletion     contributing to germline MLH1 hypermethylation, and to Lynch syndrome tumoral     --over   in gastric cancer tissues and cell lines tumoral     --over   is the unfavorable predictor for the shorter overall survival (OS) and disease-free survival (DFS) for Hepatocellular carcinoma (HCC) patients constitutional       loss of function loss of EPCAM may cause the reduction and mislocalization of proteins that compose adherens junctions partly via the downregulation of nectin 1 in the intestines

Susceptibility

Variant & Polymorphism

Candidate gene
Marker	significant prognostic factor in pancreatic cancer patients by suppressing cell activity, and its expression was found to be related to the suppression of pancreatic cancer cell activity and the good prognosis in pancreatic cancer patients receiving the curative resection
	marker highly expressed in carcinomas and showing a strong correlation with poor cancer prognosis
Therapy target
	System Type Disorder Pubmed cancer eye   target for therapy in retinoblastoma cancer digestive stomach potential value of EPCAM in the therapy of gastric cancer in clinic

ANIMAL & CELL MODELS

EpCAM-/- embryos become nonviable because of placental insufficiency resulting from attenuated development of the labyrinthine layer, a process that involves invasion of fetal elements into the maternal decidua