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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
Corresponding disease
HDGC hereditary diffuse gastric carcinoma
MRCPH mental retardation, cleft palate, heart malformation
Location 16q22.1      Physical location : 68.771.194 - 68.869.444
Synonym name
  • calcium-dependent adhesion protein, epithelial
  • uvomorulin
  • CD324 antigen
  • cell-CAM 120/80
  • cell surface adhesion protein epithelial (E)-cadherin
  • E-Cadherin
    • Synonym symbol(s) CDHE, UVO, ECAD, LCAM, CAD1, Arc-1, CD324,
    DNA
    TYPE functioning gene
    STRUCTURE 98.25 kb     16 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    cytosine-phosphate-guanine/HTF
    text structure
  • E-box element in the proximal promoter
  • CDC6 repressed CDH1 transcription by binding to the E-boxes of its promoter, leading to dissociation of the chromosomal insulator CTCF, displacement of the histone variant H2A.Z, and promoter heterochromatinization
  • region of the promoter bound by KLF4 which is necessary for the activation of theCDH1 promoter activity after KLF4 overexpression, and promoter contains several CACCC sequences and a GC-rich region, located between the two ZEB2 binding sites
    • MAPPING cloned Y linked N status confirmed
    Map see TSG16H
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    16 - 4815 - 882 - 1988 3263290
    preproprotein
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveesophagus   highly
     mouthpalate  highly Homo sapiensFetal
    Reproductivefemale systembreastmammary gland highly
    Urinarykidneynephronrenal capsuleglomerulus  Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialbarrier lining    Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Skin/Tegumentkeratinocyte
    Urinarypodocyte 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)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein 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
    SystemTypeDisorderPubmed
    osteoarticularboneostéoporosis
    is a potential therapeutic option for treatment of osteoporosis
    ANIMAL & CELL MODELS
    important adhesion molecule for chick retinal ganglion cells neurite outgrowth