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FLASH GENE

Symbol

CDH1

contributors: mct - updated : 14-12-2018

HGNC name	cadherin 1, type 1, E-cadherin (epithelial)
HGNC id	1748

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_004360 16 - 4815 NP_004351 - 882 - 1988 3263290 preproprotein

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 esophagus       highly   mouth palate     highly Homo sapiens Fetal Reproductive female system breast mammary gland   highly Urinary kidney nephron renal capsule glomerulus   Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Epithelial barrier lining       Homo sapiens

cells

System Cell Pubmed Species Stage Rna symbol Skin/Tegument keratinocyte Urinary podocyte Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

embryo

Text	in the frontonasal prominence

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	N terminal hydrophobic domain
	five extracellular cadherin repeats with four cysteines in the most proximal (MPED)
	a transmembrane segment (TM) and a highly conserved cytoplasmic tail required for interactions
	a juxtamembrane domain (JMD) are thought to be involved in regulating CDH1 internalization and degradation
	C terminal catenin binding domain

conjugated

GlycoP

mono polymer

homomer , dimer

HOMOLOGY

interspecies	ortholog to murine Cdh1
	ortholog to rattus cdh1

Homologene

FAMILY

cadherin superfamily of calcium dependent cell-cell adhesion glycoproteins

CATEGORY

adhesion

SUBCELLULAR LOCALIZATION	extracellular
	plasma membrane,junction,adherens
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,organelle,Golgi
	intracellular,cytoplasm,organelle,endosome
text	type I membrane protein
	in epithelial cells, concentrated within adherens junctions, where the components of the adherens complex interact with the actin cytoskeleton
	is a major cell–cell adhesion molecule present in adherens junctions

basic FUNCTION	tumor suppressor gene downregulator of cell growth
	calcium dependent cell adhesion molecule involved in cell-cell or cell-ECM interactions
	playing a critical role in WNT signaling and in tumorigenesis
	playing a major role in intercellular adhesion, cell polarity and tissue architecture
	playing a major role in craniofacial morphogenesis
	invasion-suppressor and its loss is an indicator of high tumor aggressivness
	required to form the first lateral membrane domains in development
	play an essential role in maintaining epithelial polarity by forming Ca2+-dependent adherens junctions between epithelial cells
	in addition to suppressing late-stage tumor progression, CDH1-mediated adherens junctions may also contribute to the initial emergence of a cohesive morphogenic phenotype that is a hallmark of differentiated epithelial ovarian carcinoma
	involved in cell adhesion and has distinct roles in the regulation of intercellular communication between beta-cells within islets, with potential repercussions for insulin secretion
	required for assembly of a robust spindle midzone at anaphase and for normal timings of spindle elongation and cytokinesis
	cell–cell adhesion molecule that plays a pivotal role in epithelial cell invasion and acts as major contributor to cancer progression
	regulates MGAT3 gene transcription and leads to a significant up-regulation of its mRNA transcription levels
	plays an important role in the maintenance of tissue integrity
	plays a key role in mitotic exit and has essential targets in the G(1) phase
	a novel and crucial role for PAK1 and CDH1 endocytosis in determining lumen size and shape, and also identify a mechanism for multiple lumen formation, a poorly understood process that occurs in salivary gland normal embryonic development and pathological conditions
	CDH6 functions as an inhibitor of tubulogenesis, whereas CDH1 is required for lumen formation
	cell-adhesion molecule, having important functions in pluripotency and reprogramming
	CDH1/catenin complex functions as an upstream regulator of the Hippo signaling pathway in mammalian cells
	in addition to its role in cell-cell adhesion, CDH1-mediated cell-cell contact directly regulates the Hippo signaling pathway to control cell proliferation
	its expression in cancer cells is controlled by a balance between ZEB2 and KLF4 expression levels

CELLULAR PROCESS	cell cycle

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

	pathway for the control of anoikis sensitivity by CDH1 and epithelial-to-mesenchymal transition
	CDH1-ANAPC/SMURF1/RHOA pathway that mediates axonal growth suppression in the developing mammalian brain
	METTL3/ZMYM1/CDH1 signaling is a potential therapeutic target in anti-metastatic strategy against gastric cancer

a component	constituent of transmembrane glycoprotein major adhesion receptor component of adherens junction
	complexing with CTNNB1, TCF
	component of lateral membranes in epithelial tissues

INTERACTION

DNA

RNA

small molecule	metal binding,
	ion CA2+

protein	hemophilic, calcium dependent interactions
	interacting by its C terminus with the cytoskeleton via beta-catenin
	interacting with MGAT3, MGAT5 (regulatory mechanism between CDH1, MGAT3 and MGAT5 by enzymatic competition which could underlie a possible novel signaling pathway in carcinogenesis)
	ligand for integrin alpha-E/beta-7
	interacting with PVRL1
	binds directly to ANK3 and this interaction is required for exit of CDH1 from the trans-Golgi network and for maintenance at the lateral membrane of cultured epithelial cells
	activated CDC2 binds to E-cadherin in a GTP-dependent manner, and the binding of Cdc42 is essential for CDC42 to induce the dissolution of adherens junctions
	role for SNX1 in retrieval of CDH1 from a degradative endosomal pathway and in membrane trafficking pathways that regulate CDH1 recycling
	targeting of Aurora kinases at anaphase by APC/C(CDH1) participates in the control of mitotic exit and cytokinesis
	correlation between CBX7 and E-cadherin (CDH1) expression in thyroid carcinomas
	interaction between DDB1 and CDH1 plays a critical role in regulating APC/CDH1 activity
	USP37 binds CDH1 and removes degradative polyubiquitin from cyclin A
	interacting with GNB2L1 (GNB2L1 has a novel function in maintaining the junctional homeostasis of intestinal epithelial cells by regulation of the SRC- and growth factor-induced endocytosis of CDH1)
	novel roles for IRS2 and FOXO3 in the regulation of kidney epithelial cells by CDH1
	EPHB1, EPHB3, interact with E-cadherin and with the metalloproteinase ADAM10 at sites of adhesion and their activation induces shedding of CDH1 by ADAM10 at interfaces with EPHB1-expressing cells
	GAB2 inhibits CDH1 expression and enhances the expression of ZEB1, a transcription factor involved in epithelial-to-mesenchymal transition (EMT), and cell migration and invasion through the activation of the PI3K pathway
	TCF12 functioned as a transcriptional repressor of CDH1 and its overexpression was significantly correlated with the occurrence of CRC metastasis
	TCF12 functions as a regulator of EMT by affecting the expression of CDH1 as well as that of GJA1 and GJB2
	promotes the E3 ligase activity of SMURF1 (upstream component that governs SMURF1 activity)
	SNAI1 enhances the binding of AKT2 to the E-cadherin (CDH1) promoter and AKT2 interference prevents SNAI1 repression of CDH1 gene
	ATR can have a central role in inhibiting the initiation of DNA replication by the regulation of CDC6 by CDH1
	ZEB1 may mediate STAT3-induced down-regulation of CDH1 via directly inhibiting transcriptional activity of the CDH1 promoter in colorectal cancer
	ETV5 modulated ZEB1 expression and CDH1 repression leading to a complete reorganization of cell-cell and cell-substrate contacts
	is a key regulator of CDH1 expression, and thereby contributes to the stability of intercellular junctions
	WASF2 is recruited to the zonula adherens (ZA) in response to CDH1 adhesion
	CDH1 expression is repressed by ZEB2 while it is induced by KLF4
	switch from activation of the anaphase-promoting complex/cyclosome (APC/C) by CDC20 to CDH1 during anaphase is crucial for accurate mitosis
	CDH1 was found to be involved in the PSMD10 induced invasion of breast cancer cells due to hypoxia
	PROM1 associates with membrane CTNNB1 in early placodes, and its continued expression correlates with loss of CTNNB1 and CDH1 from the cell membrane at a time when CDH1 transcriptional repressors SNAI1 and SNAI2 are not implicated
	cooperative functions of the two F-BAR proteins TRIP10 and NOSTRIN in the regulation of CDH1 in epithelial morphogenesis
	CDH1 is a novel ADAM12 substrate
	CDH1 promotes nucleotide excision repair through positively regulating the expression of xeroderma pigmentosum complementation group C (XPC) and DNA damage-binding protein 1 (DDB1)
	AHNAK is required for the expression of functional CDH1
	major role for GRHL3 in the induction of migration and invasion by the downregulation of CDH1 in cancer cells
	ANXA1 promotes the proliferation of esophageal squamous cell carcinoma (ESCC) cells, and increases the expression of SNAI1, whereas it inhibits that of CDH1, thus enhancing the migration and invasion of ESCC cells
	DSC3 suppresses Colorectal cell growth through inhibition of AKT1 pathway and regulation of CDH1
	HSPD1 might repress CDH1 expression and promote metastatic characters of Buccal mucosa squamous cell carcinoma (BMSCC) cells for poor prognosis of BMSCC patients
	S100P contribute to a cancer pathway dependent on the context of CDH1 function
	S100P has a dual role in gastric cancer, acting as an oncogenic factor in the context of CDH1 loss and as a tumour suppressor in a functional CDH1 setting

cell & other

REGULATION

induced by	WNT7A in lung cancer cells
		KLF4 binding to the GC-rich/E box region of the promoter

inhibited by	TCF8 only in cancer cell lines
	GH1 that decreases CDH1 expression in the glomerular podocyte

repressed by	SNAI1, SNAI2
		MPHOSPH8 which represses E-cadherin expression through DNA methylation
		ZEB2, a transcriptional repressor of CDH1 and CDH3 gene expression

Other	cleavage by ADAM10 mediates epithelial cell sorting downstream of EPHB signalling
	cleavage by MMP20 (cleaves CDH1 and influences ameloblast development)
	ubiquitination of the JMD inhibits CTNND1 binding, and targets CDH1 for degradation

ASSOCIATED DISORDERS

corresponding disease(s)

HDGC , MRCPH

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral   deletion     during development of carcinomas (see TSG16H and TSG16A) tumoral somatic mutation       mutated in signet ring cell carcinoma of stomach (with poor clinical outcome), in colorectal, intestines and lobular breast cancers (see TSG16A) tumoral   LOH     aberrant methylation of the promoter leading to LOH in gastric cancer and in ulcerative colitis with potential progression to colorectal cancer tumoral germinal mutation     loss of function loss of function by germinal mutation in sporadic, early-onset diffuse gastric carcinoma and colorectal, breast, prostate cancer (late stage) tumoral   LOH     in invasive breast lobular carcinoma with or without gene mutation tumoral     --low   in invasive and metastatic gastric tumours, but enhanced motility and invasion associated with mutant CDH1 is sensitive to inhibition of RAC1 and RHOA, RHOB tumoral     --over   in ovarian carcinoma cells, associated with increased CDH1 promoter activity, increased adherens junction formation, decreased beta-catenin signaling-dependent LEF1 activity tumoral     --low   required to initiate metastatic outgrowth of breast cancer constitutional     --low   is a key initiating event in EMT (epithelial-mesenchymal transition) tumoral     --low   were significantly decreased in oral squamous cell carcinoma cells that expressed SNAIl tumoral     --low   by hypermethylation in B-cell lymphoma

Susceptibility

to listeria monocytogenes to cleft lip, with or without cleft palate to recurrence of bladder cancer to primary open angle glaucoma to prostate cancer

Variant & Polymorphism SNP , insertion/deletion	single-nucleotide polymorphism in the promoter modifiyng the risk of prostate cancer
	deletion, removing the extracellular cadherin repeat domains, associated to cleft lip/palate in families with hereditary diffuse gastric cancer
	promoter polymorphism (C-160A)increasing the risk of recurrence of bladder cancer
	3'-UTR C/T polymorphism associated with primary open angle glaucoma
	the C/A variant -160 base pairs associated with prostate cancer risk, and bladder cancer risk

Candidate gene	detection of methylation of the gene in blood might have utility in monitoring and detecting tumor recurrence in early-stage non-small cell lung cancer after curative surgical resection
Marker	represent promising epigenetic markers which may be suitable for monitoring of B-cell lymphoma
Therapy target
	System Type Disorder Pubmed osteoarticular bone ostéoporosis is a potential therapeutic option for treatment of osteoporosis

ANIMAL & CELL MODELS

important adhesion molecule for chick retinal ganglion cells neurite outgrowth