Affinage

CD82

CD82 antigen · UniProt P27701

Length
267 aa
Mass
29.6 kDa
Annotated
2026-04-28
100 papers in source corpus 36 papers cited in narrative 37 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CD82/KAI1 is a tetraspanin that functions as a metastasis suppressor and membrane microdomain organizer, controlling cell migration, invasion, adhesion, and angiogenesis by reorganizing lipid raft and ganglioside-enriched domains to modulate receptor tyrosine kinase signaling, integrin trafficking, and actin cytoskeleton dynamics. CD82 attenuates EGFR dimerization by redistributing it into ganglioside-enriched membrane fractions, suppresses HGF/cMet activation through GM2/GM3–CD82 glycosynaptic complexes, promotes integrin α6 and α4 internalization or clustering in a palmitoylation-dependent manner, and inhibits cell motility by reducing Rac1 and RhoA activity and disrupting the p130CAS–CrkII signaling switch (PMID:14576349, PMID:18272501, PMID:15557282, PMID:24623721, PMID:23251627, PMID:12738793). Its expression is transcriptionally activated by p53, ΔNp63α, and Tip60/Pontin complexes downstream of PKC–MEK–ERK signaling, and its protein stability is regulated by palmitoylation at cytoplasmic cysteines and by gp78 E3 ligase-mediated proteasomal degradation (PMID:9736732, PMID:24901051, PMID:19048121, PMID:15492270, PMID:20089858). Beyond its anti-metastatic role, CD82 regulates innate immune signaling by facilitating TLR9 trafficking and myddosome assembly in macrophages and suppressing NLRP3 inflammasome activation by blocking BRCC3-mediated deubiquitination of NLRP3 (PMID:31408613, PMID:36600050).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1995 High

    Identification of KAI1/CD82 as a metastasis suppressor gene established that a tetraspanin could directly suppress cancer dissemination in vivo, opening the question of how a transmembrane scaffold protein achieves this.

    Evidence Gene transfer into metastatic rat AT6.1 prostate cancer cells with in vivo metastasis assay

    PMID:7754374

    Open questions at the time
    • Mechanism of metastasis suppression unknown
    • Downstream signaling pathways not identified
    • Relevant interacting partners not yet defined
  2. 1998 High

    Discovery that p53 directly activates KAI1/CD82 transcription linked metastasis suppression to the p53 tumor suppressor network, explaining how KAI1 is silenced in cancers with p53 loss.

    Evidence EMSA with purified p53, promoter-reporter assay, and site-directed mutagenesis of p53 binding site

    PMID:9736732

    Open questions at the time
    • Other transcriptional regulators of KAI1 not yet identified
    • Mechanism by which CD82 protein suppresses metastasis still undefined
  3. 2003 High

    Convergent studies revealed that CD82 reorganizes plasma membrane microdomains to attenuate EGFR dimerization, disrupts the p130CAS–CrkII motility switch, and partners with EWI2/PGRL, collectively establishing membrane compartmentalization and adhesion signaling as the core mechanisms of metastasis suppression.

    Evidence Sucrose gradient fractionation and Co-IP for EGFR compartmentalization; p130CAS overexpression rescue of migration; chemical cross-linking/MS for EWI2 stoichiometric association

    PMID:12738793 PMID:12750295 PMID:14576349

    Open questions at the time
    • How CD82 remodels lipid domains mechanistically (lipid species involved) not yet defined
    • Whether p130CAS downregulation is transcriptional or post-translational unclear
  4. 2004 High

    Palmitoylation at all cytoplasmic cysteines was shown to be essential for CD82 integration into tetraspanin-enriched microdomains and its anti-migratory and anti-invasive functions, establishing a critical post-translational regulatory mechanism.

    Evidence ³H-palmitate metabolic labeling, cysteine-to-alanine mutagenesis with migration/invasion and Co-IP readouts

    PMID:15492270

    Open questions at the time
    • Palmitoyltransferase responsible not yet identified (zDHHC4 identified later)
    • Whether palmitoylation is dynamically regulated in response to signals unknown
  5. 2004 High

    Demonstration that CD82 promotes integrin α6 internalization without altering total protein levels revealed a trafficking-based mechanism for reducing cell adhesion, extending the model beyond signaling attenuation to receptor surface regulation.

    Evidence Co-IP, surface biotinylation, and integrin internalization assay in epithelial cells

    PMID:15557282

    Open questions at the time
    • Endocytic route for integrin internalization not characterized
    • Whether other integrins are similarly affected not systematically tested
  6. 2008 High

    Identification of the GM2/GM3 ganglioside heterodimer as a functional partner of CD82 that inhibits HGF/cMet signaling provided a molecular explanation for how glycolipid–tetraspanin interactions suppress receptor tyrosine kinase activation in glycosynaptic microdomains.

    Evidence ESI-MS of ganglioside complex, cMet kinase assay, and functional rescue with anti-GM2/GM3 blocking antibody

    PMID:18272501

    Open questions at the time
    • Whether other RTKs are similarly regulated by this ganglioside complex unknown
    • Structural basis of CD82–ganglioside interaction unresolved
  7. 2008 High

    Polar residues within CD82 transmembrane domains were shown to be required for tetraspanin web integrity (CD9/CD151 interaction) and metastasis suppression, linking protein structural features to microdomain organization.

    Evidence TM domain polar residue mutagenesis with Co-IP, in vivo metastasis assay, and conformational stability assay

    PMID:19116362

    Open questions at the time
    • No high-resolution structure of CD82 available
    • How TM polar residues mediate specific tetraspanin–tetraspanin contacts at atomic level unknown
  8. 2008 Medium

    Characterization of KAI1 promoter regulation by competing Tip60/Pontin activator and β-catenin/Reptin repressor complexes downstream of PKC–MEK–ERK signaling revealed an epigenetic switch controlling CD82 expression in prostate cancer.

    Evidence ChIP for Tip60/Pontin and Reptin at NF-κB-p50 promoter motifs, kinase inhibitor studies, histone acetylation assay

    PMID:19048121

    Open questions at the time
    • Whether this transcriptional switch operates in non-prostate contexts unclear
    • Direct interaction between β-catenin/Reptin and Tip60/Pontin at the promoter not structurally resolved
  9. 2009 High

    Discovery that CD82 itself undergoes cholesterol-dependent, clathrin-independent endocytosis to late endosomes/lysosomes — and that this endocytosis relieves its migration-inhibitory effect — established that CD82 surface levels are dynamically regulated and functionally consequential.

    Evidence Endocytosis/trafficking assays with cholesterol depletion and dominant-negative dynamin, live-cell imaging

    PMID:19497983

    Open questions at the time
    • Specific endocytic machinery mediating clathrin-independent CD82 uptake not identified
    • Signals triggering CD82 internalization in physiological contexts unknown
  10. 2010 High

    Identification of gp78 E3 ligase-mediated ERAD of CD82, with epistasis showing KAI1 knockdown rescues gp78 knockdown phenotypes, established proteasomal degradation as a key mechanism for CD82 protein level control in cancer.

    Evidence gp78 transgenic mouse, shRNA knockdown, BrdU proliferation assay, epistasis rescue

    PMID:20089858

    Open questions at the time
    • Ubiquitination sites on CD82 not mapped
    • Whether other E3 ligases target CD82 unknown
  11. 2012 High

    Mechanistic dissection of CD82's anti-migratory action showed it suppresses both Rac1 (lamellipodia) and RhoA (stress fibers/retraction) activities while reducing PIP2 at the cell periphery, unifying the cytoskeletal phenotypes under a shared membrane signaling mechanism.

    Evidence Rac1/RhoA GTPase pull-down assays, ROCK kinase assay, PIP2 imaging, live-cell imaging

    PMID:23251627

    Open questions at the time
    • How CD82 simultaneously suppresses opposing GTPases mechanistically unresolved
    • Direct effector linking CD82 to GTPase regulation not identified
  12. 2013 High

    CD82 was found to suppress EGFR ubiquitylation by increasing PKC-dependent c-Cbl phosphorylation in a ligand-selective manner (HB-EGF/amphiregulin but not EGF), refining understanding of how CD82 modulates RTK signaling at the post-activation level.

    Evidence Ubiquitylation assay, EEA1 endosome colocalization, C-terminal deletion mutant, phospho-specific antibodies

    PMID:23897813

    Open questions at the time
    • Why ligand selectivity exists (HB-EGF vs EGF) not mechanistically explained
    • Whether reduced EGFR ubiquitylation promotes degradation or recycling not resolved
  13. 2014 High

    Superresolution imaging showed CD82 increases molecular packing density of α4 integrin clusters in a palmitoylation-dependent manner, providing the first nanoscale visualization of how a tetraspanin organizes integrin membrane architecture to regulate HSPC adhesion.

    Evidence dSTORM superresolution imaging, clustering algorithms, palmitoylation-deficient mutant, cell adhesion assay

    PMID:24623721

    Open questions at the time
    • Whether CD82 similarly organizes other integrins at the nanoscale not tested
    • Structural basis for palmitoylation-dependent integrin clustering unknown
  14. 2014 High

    ΔNp63α was identified as a direct transcriptional activator of CD82, with CD82 knockdown reversing ΔNp63α-mediated invasion suppression, connecting CD82 to the p63 family of transcription factors beyond p53.

    Evidence ChIP, expression profiling, siRNA knockdown rescue, invasion assay

    PMID:24901051

    Open questions at the time
    • Whether p53 and ΔNp63α compete or cooperate at the CD82 promoter unknown
    • Relevance in non-epithelial cell types not established
  15. 2018 High

    CD82 knockout in HSPCs revealed Rac1 hyperactivation causing defective bone marrow homing and quiescence loss, rescued by Rac1 inhibition, demonstrating that CD82's restraint of Rac1 is physiologically essential for stem cell function beyond cancer.

    Evidence CD82 KO mouse, Rac1 activity assay, bone marrow transplantation, Rac1 inhibitor rescue

    PMID:30133344

    Open questions at the time
    • How CD82 restrains Rac1 activity molecularly (direct vs indirect) not defined
    • Whether quiescence defect contributes to long-term HSC exhaustion not tested
  16. 2019 High

    CD82 was shown to regulate innate immunity by associating with TLR9 from the ER through endosomal compartments and being required for myddosome formation and NF-κB activation, revealing a non-cancer function in immune signaling.

    Evidence Co-IP, confocal microscopy, myddosome formation assay, NF-κB translocation, CD82-deficient macrophages

    PMID:31408613

    Open questions at the time
    • Whether CD82 regulates other TLRs beyond TLR9 not tested
    • Mechanism by which CD82 enables myddosome assembly not defined
  17. 2023 Medium

    CD82 was found to suppress NLRP3 inflammasome activation by binding both NLRP3 and BRCC3 deubiquitinase, blocking K63 deubiquitination and promoting NLRP3 degradation — establishing CD82 as a negative regulator of inflammasome signaling.

    Evidence Co-IP with NLRP3 and BRCC3, ubiquitination assay, CD82 KO mice with colitis model

    PMID:36600050

    Open questions at the time
    • Whether CD82 bridges NLRP3 and BRCC3 as a ternary complex or competes for binding not resolved
    • Single study — independent replication needed
    • Structural basis of CD82–BRCC3 interaction unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • The molecular mechanism by which CD82 simultaneously restrains multiple GTPases (Rac1, RhoA, Cdc42), the structural basis of its tetraspanin web interactions, and the relative contributions of its diverse signaling outputs to metastasis suppression in vivo remain unresolved.
  • No high-resolution structure of CD82 in a membrane context
  • No systematic in vivo epistasis distinguishing contributions of individual effector pathways
  • How CD82 coordinates cancer-cell-autonomous vs microenvironmental (endothelial, immune) functions is unclear

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 8 GO:0008289 lipid binding 3 GO:0060090 molecular adaptor activity 2
Localization
GO:0005886 plasma membrane 10 GO:0005768 endosome 2 GO:0005783 endoplasmic reticulum 2
Pathway
R-HSA-162582 Signal Transduction 6 R-HSA-1500931 Cell-Cell communication 3 R-HSA-168256 Immune System 3 R-HSA-9609507 Protein localization 3
Partners
ADAM17BRCC3EGFRIGSF8ITGA4ITGA6NLRP3TLR9
Complex memberships
GM2/GM3-CD82 glycosynaptic complextetraspanin-enriched microdomain (TEM)

Evidence

Reading pass · 37 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 KAI1/CD82 was identified as a metastasis suppressor gene encoding a 267-amino acid protein with four transmembrane domains and one large extracellular hydrophilic domain with N-glycosylation sites, belonging to the tetraspanin/transmembrane 4 superfamily; introduction of KAI1 into metastatic rat prostate cancer cells suppressed metastasis in vivo. Gene transfer into rat AT6.1 prostate cancer cells, in vivo metastasis assay, molecular cloning Science High 7754374
1998 The tumor suppressor p53 directly activates KAI1/CD82 transcription by binding to a tandem p53 consensus sequence ~860 bp upstream of the transcriptional initiation site, as demonstrated by gel-shift mobility assay with purified p53 protein and mutational analysis of the binding sequence. Gel-shift mobility assay (EMSA), promoter-reporter assay, site-directed mutagenesis, immunohistochemistry Proceedings of the National Academy of Sciences of the United States of America High 9736732
2003 CD82 specifically attenuates ligand-induced dimerization of EGFR and causes redistribution of EGFR into lipid raft-like light sucrose gradient fractions enriched in gangliosides GD1a and GM1; the large extracellular loop of CD82 alone is insufficient for this effect, implicating other domains. CD82 is also associated with ErbB2 and ErbB3 but does not affect ErbB2-ErbB3 dimerization. Sucrose gradient fractionation, co-immunoprecipitation, confocal microscopy, expression of recombinant CD82 domains Journal of cell science High 14576349
2003 KAI1/CD82 inhibits cancer cell migration by downregulating p130CAS protein levels, thereby reducing formation of the p130CAS-CrkII complex (a 'molecular switch' in cell motility); overexpression of p130CAS in KAI1/CD82-expressing cells restored migration, confirming the pathway. Stable transfection, Western blot, co-immunoprecipitation, migration assay, p130CAS overexpression rescue experiment The Journal of biological chemistry High 12738793
2003 EWI2/PGRL (an immunoglobulin superfamily member) directly and stoichiometrically associates with KAI1/CD82 in a cholesterol-independent, likely direct interaction; overexpression of EWI2/PGRL inhibits prostate cancer cell migration and synergizes with KAI1/CD82 in migration suppression. Chemical cross-linking, co-immunoprecipitation, mass spectrometry peptide sequencing, migration assay, cholesterol depletion Cancer research High 12750295
2003 C33/CD82/KAI1 induces apoptosis by generating reactive oxygen intermediates (ROIs) via a non-mitochondrial pathway; it promotes cell death by causing release of intracellular antioxidant glutathione (GSH) from cells and activates the GTPase Cdc42, which mediates GSH release and apoptosis induction. Apoptosis screen (gain-of-function), ROI detection, GSH measurement, Cdc42 activation assay FASEB journal Medium 14597553
2003 KAI1/CD82 promotes homotypic aggregation of prostate cancer cells through a Src kinase-dependent intracellular signaling pathway; ligation of CD82 increases endogenous Src kinase activity, and a kinase-negative Src mutant abolished CD82-mediated aggregation. Stable transfection, kinase-negative Src mutant re-transfection, antibody-induced CD82 cross-linking, Src kinase activity assay Experimental & molecular medicine Medium 12642901
2004 KAI1/CD82 is palmitoylated at all cytoplasmic cysteine residues proximal to the plasma membrane; palmitoylation-deficient CD82 mutant largely reverses inhibitory effects on migration and invasion, disrupts tetraspanin web association, alters subcellular distribution, and abolishes inhibition of lamellipodia formation and p130CAS-CrkII coupling. [3H]-palmitate metabolic labeling, site-directed mutagenesis of cysteine residues, migration/invasion assay, co-immunoprecipitation, actin cytoskeleton imaging Cancer research High 15492270
2004 CD82 attenuates integrin α6-mediated cell adhesion and morphogenesis by associating with integrin α6 and promoting its internalization, thereby reducing α6 integrin surface expression without changing total cellular α6 protein levels. Co-immunoprecipitation, surface biotinylation, internalization assay, Matrigel morphogenesis assay, integrin-blocking antibodies The Journal of biological chemistry High 15557282
2004 KITENIN/VANGL1, a tetraspanin family member, interacts specifically with the C-terminal cytoplasmic domain of KAI1 (identified by yeast two-hybrid); KITENIN overexpression increases tumor invasiveness and metastasis, antagonizing KAI1 metastasis suppressor function. Yeast two-hybrid screening, in vivo metastasis model, invasion and adhesion assays Cancer research Medium 15205336
2008 Ganglioside GM2/GM3 complex (heterodimer stabilized by Ca2+) interacts with CD82 in glycosynaptic microdomains to inhibit HGF-induced cMet tyrosine kinase activity and cell motility; an antibody blocking GM2/GM3 dimer-CD82 interaction restores cell motility, confirming functional specificity. ESI mass spectrometry, cell motility assay, cMet kinase activity assay, blocking antibody (mAb 8E11), nanosphere coating with glycosphingolipids Proceedings of the National Academy of Sciences of the United States of America High 18272501
2008 CD82 requires polar residues (Asn, Gln, Glu) within its transmembrane domains for its migration-, invasion-, and metastasis-suppressive activities; mutation of these residues disrupts interaction with tetraspanins CD9 and CD151 (but not α3β1 integrin association), reduces conformational stability, and abolishes inhibition of microprotrusion formation and microvesicle release. Site-directed mutagenesis of TM domain polar residues, co-immunoprecipitation, in vivo metastasis assay, structural modeling, denaturation assay The American journal of pathology High 19116362
2009 CD82 undergoes cholesterol-dependent, dynamin- and clathrin-independent endocytosis to late endosomes and lysosomes; cholesterol depletion blocks CD82 internalization. CD82 also redistributes cholesterol into tetraspanin-enriched microdomains (TEMs), reorganizing TEMs and lipid rafts. CD82 endocytosis alleviates its inhibitory effect on cell migration. Endocytosis/trafficking assays, cholesterol depletion (methyl-β-cyclodextrin), dominant-negative dynamin expression, sucrose gradient fractionation, live-cell imaging FASEB journal High 19497983
2010 The E3 ubiquitin ligase gp78 targets KAI1/CD82 for degradation via ER-associated degradation (ERAD); gp78 overexpression reduces KAI1 expression and gp78 knockdown increases KAI1 expression; gp78 regulation of cell proliferation is mediated by KAI1, demonstrated by KAI1 knockdown rescuing reduced proliferation in stable gp78 knockdown cells. MMTV-gp78 transgenic mouse model, siRNA/shRNA knockdown, Western blot, BrdU proliferation assay, epistasis rescue experiment The Journal of biological chemistry High 20089858
2012 KAI1/CD82 inhibits cell migration by attenuating the plasma membrane-dependent actin organization: it reduces Rac1 activity (diminishing lamellipodia and actin cortical network), blocks growth factor-stimulated RhoA activity (preventing stress fiber formation and retraction), reduces cofilin enrichment at the cell periphery, and decreases Rho kinase activity. Additionally, phosphatidylinositol 4,5-bisphosphate becomes less detectable at the cell periphery. Live imaging, Rac1/RhoA activity assays (pull-down), ROCK kinase assay, phospholipid imaging, stable transfection PloS one High 23251627
2013 CD82/KAI1 suppresses ubiquitylation of EGFR after stimulation with heparin-binding EGF or amphiregulin (but not EGF itself), delays EGFR recruitment to EEA1-positive early endosomes, and increases PKC-dependent serine phosphorylation of c-Cbl E3 ubiquitin ligase; phosphorylation of EGFR Thr654 (PKC site) is also increased in CD82-expressing cells. The C-terminal cytoplasmic domain of CD82 is required for its endocytic trafficking and this regulatory function. Ubiquitylation assay, endocytic trafficking assay (EEA1 co-localization), C-terminal deletion mutant (CD82ΔC), phospho-specific antibodies, Western blot The Journal of biological chemistry High 23897813
2013 CD82 positively regulates the STAT5/IL-10 signaling pathway in leukemia stem cells: CD82 knockdown dephosphorylates STAT5 and decreases IL-10 levels, while forced CD82 expression increases p-STAT5 and IL-10; ChIP assay demonstrates STAT5A binds to the IL-10 gene promoter, and reporter assay confirms transcriptional activation of IL-10 by CD82-driven STAT5. shRNA knockdown, lentiviral overexpression, ChIP assay, luciferase reporter assay, Western blot International journal of cancer Medium 23797738
2014 CD82 overexpression increases the molecular density of α4 integrin subunits within plasma membrane clusters, thereby increasing cell adhesion; this packing depends on CD82 palmitoylation and the presence of α4 integrin ligands. CD82 regulates HSPC adhesion and homing to bone marrow through modulation of integrin membrane organization. Direct stochastic optical reconstruction microscopy (dSTORM) superresolution imaging, protein clustering algorithms, palmitoylation-deficient mutant, cell adhesion assay Molecular biology of the cell High 24623721
2014 ΔNp63α directly transcriptionally activates CD82/KAI1 as a target gene to inhibit cancer cell invasion; chromatin immunoprecipitation confirmed ΔNp63α binding to the CD82 promoter; CD82 knockdown reversed ΔNp63α-mediated invasion suppression; GSK3β inhibition downregulates both ΔNp63α and CD82 independently of β-catenin. ChIP, Affymetrix gene expression profiling, siRNA knockdown rescue, Matrigel invasion assay, luciferase reporter Cell death & disease High 24901051
2014 CD82 restrains angiogenesis in endothelial cells by inhibiting lipid raft clustering and CD44 membrane trafficking; CD82 ablation increases ganglioside levels and lipid raft clustering in the plasma membrane, reduces clathrin-independent endocytosis of CD44, and elevates CD44 surface expression, leading to enhanced outside-in signaling and EC migration. Cd82-null mouse model, in vivo and ex vivo angiogenesis assays, lipid raft fractionation, CD44 trafficking assay, ganglioside analysis Circulation High 25149363
2016 CD82 suppresses U2AF2-mediated CD44 alternative splicing (specifically CD44v8-10 production) by inducing ubiquitination and degradation of the splicing factor U2AF2, thereby inhibiting melanoma metastasis; U2AF2-dependent CD44v8-10 promotes migration via Src/FAK/RhoA activation and CD44-E-selectin binding. In vivo metastasis assay, in vitro migration, ubiquitination assay, siRNA knockdown, Affymetrix expression, immunoprecipitation Oncogene High 27041584
2017 CD82 inhibits fibronectin-induced epithelial-to-mesenchymal transition (EMT) in prostate cancer cells by forming lateral interactions with fibronectin-binding α3β1 and α5β1 integrins and attenuating downstream FAK-Src and ILK signaling pathways. Co-immunoprecipitation, immunofluorescence, Western blot for FAK/Src/ILK phosphorylation, invasion/migration assay, human tissue immunostaining Oncotarget Medium 27926483
2018 CD82 deficiency in hematopoietic stem and progenitor cells (HSPCs) causes hyperactivation of Rac1, impaired bone marrow homing and engraftment, and reduced stem cell quiescence (cell cycle activation); pharmacological Rac1 inhibition rescues the homing defect of CD82KO HSPCs. CD82 knockout mouse model, Rac1 activity assay, bone marrow transplantation homing assay, cell cycle analysis, Rac1 inhibitor rescue Molecular biology of the cell High 30133344
2019 CD82 is a key regulator of TLR9 trafficking and signaling: CD82 associates with TLR9 in the endoplasmic reticulum and post-ER compartments in macrophages; CD82 is essential for CpG-stimulated TLR9-dependent myddosome formation and NF-κB nuclear translocation leading to inflammatory cytokine production. Co-immunoprecipitation, confocal microscopy, myddosome formation assay, NF-κB nuclear translocation assay, cytokine measurement, CD82-deficient macrophages FASEB journal High 31408613
2019 CD82 represses TGF-β1/Smad signaling and Wnt/β-catenin signaling to suppress EMT in prostate cancer: CD82 blocks Smad2 phosphorylation, Smad4 nuclear translocation, and TRE promoter transactivation; it also prevents GSK-3β inactivation downstream of Wnt3a, maintaining β-catenin phosphorylation and blocking its nuclear translocation. Luciferase reporter assay (TRE and Tcf/Lef promoters), subcellular fractionation, confocal immunofluorescence, Western blot, invasion assay The Prostate Medium 31212375
2021 KAI1/CD82 expressed in pericytes inhibits angiogenesis through two mechanisms: (1) it localizes to the membrane surface after palmitoylation by zDHHC4 and induces LIF production through the Src/p53 pathway, with secreted LIF suppressing angiogenic factors in endothelial cells; (2) CD82 directly binds VEGF and PDGF and inhibits activation of their receptors. A peptide derived from the large extracellular loop of CD82 reproduces anti-angiogenic effects in vivo. Kai1 knockout mice, in vitro/in vivo angiogenesis assay, direct binding assay (VEGF/PDGF), palmitoylation assay, Src/p53 pathway analysis, LIF measurement Journal of hematology & oncology Medium 34530889
2023 CD82 suppresses NLRP3 inflammasome activation by binding both NLRP3 and BRCC3 (a K63-specific deubiquitinase); CD82 binding blocks BRCC3-dependent K63 deubiquitination of NLRP3, promoting NLRP3 degradation. CD82 deficiency elevates NLRP3 inflammasome activation and reduces colitis severity in mice. Co-immunoprecipitation (NLRP3 and BRCC3 binding partners), CD82 KO mice, NLRP3 inflammasome activation assay, ubiquitination assay, in vivo colitis model Cellular & molecular immunology Medium 36600050
2020 CD82 interacts with ADAM17 metalloprotease and inhibits its metalloprotease activity, thereby suppressing ADAM17-mediated E-cadherin ectodomain cleavage from the cell membrane and reducing prostate cancer cell migration. Co-immunoprecipitation, ADAM17 metalloprotease activity assay, E-cadherin shedding assay, migration assay Disease markers Medium 33204367
2011 CD82 inhibits invasiveness of endometrial stromal cells by downregulating CCL2 secretion and CCR2 expression via MAPK and integrin-β1 signaling pathways, and in turn upregulating TIMP1 and TIMP2 in an autocrine manner; TCDD and 17β-estradiol promote invasion by suppressing CD82 expression. siRNA knockdown, invasion assay, MAPK inhibition, Western blot for TIMP1/TIMP2/CCL2 Journal of molecular endocrinology Medium 21685244
2006 KAI1/CD82 overexpression in H1299 lung carcinoma cells suppresses tumor invasiveness by inducing MMP9 inactivation through upregulation of TIMP1, while MMP9 mRNA and protein levels are paradoxically elevated. Stable transfection, invasion assay, gelatin zymography, RT-PCR, Western blot Biochemical and biophysical research communications Medium 16488391
2012 CD82 inhibits trophoblast invasion and migration by suppressing MMP9 gelatinolytic activity; CD82 siRNA enhances trophoblast invasion/migration and MMP9 activity, while CD82 overexpression decreases both, in villous explant and HTR8/SVneo trophoblast cell models. siRNA knockdown, CD82 overexpression, villous explant culture, invasion/migration assay, gelatin zymography PloS one Medium 22679510
2007 KAI1/CD82 suppresses HGF-induced cMet tyrosine kinase activation in the glycosynaptic microdomain as part of GM2/tetraspanin complex, inhibiting cell motility. cMet kinase activity assay, cell motility assay, glycosynaptic microdomain co-immunoprecipitation Proceedings of the National Academy of Sciences of the United States of America Medium 18272501
2007 KAI1/CD82-expressing tumor cells interact with Duffy antigen receptor for chemokines (DARC) on vascular endothelial cells, transmitting a senescent signal to cancer cells; cells that lost KAI1 expression escape this senescence and proliferate, enabling metastasis. In vitro cell-cell interaction assay, in vivo metastasis model, senescence assay Cancer research Medium 17308076
2008 KAI1/CD82 transcription in prostate cancer cells is regulated by competition between a β-catenin/Reptin repressor complex and a Tip60/Pontin activator complex at the proximal promoter; phorbol ester (PMA) induces KAI1 transcription via cPKC→MEK1/2→ERK1/2 signaling, causing recruitment of Tip60/Pontin to NFκB-p50 motifs in the promoter and enhanced histone H3 acetylation. Chromatin immunoprecipitation (ChIP), kinase inhibitor studies, histone acetylation assay, PMA stimulation Neoplasia Medium 19048121
2011 N-glycosylation of CD82 occurs at three confirmed sites (including a novel site at Asn157); the glycans include bisecting N-acetylglucosamine, α-2,6-linked N-acetylneuraminic acid, and core fucose; these glycan epitopes are relevant to cell adhesion and cancer metastasis functions of CD82. Glycosidase and protease digestion, glycan permethylation, MS analysis, site-directed mutagenesis, lectin blot Journal of proteomics Medium 22123080
2012 KAI1/CD82 suppresses HIF-1α and VEGF expression in prostate cancer by blocking CDCP1-enhanced Src kinase activation; KAI1 expression reduces CDCP1-Src signaling and increases VHL protein levels, promoting HIF-1α degradation. Stable transfection, Western blot, VEGF luciferase reporter, in vivo xenograft, immunohistochemistry BMC cancer Medium 22390300
1995 Cross-linking of CD82 together with Fc receptors on U937 monocytic cells induces a PLC-dependent increase in intracellular calcium (via PtdIns(1,4,5)P3) followed by extracellular calcium entry, and tyrosine phosphorylation of various proteins; CD82 cross-linking alone is insufficient and requires co-engagement with FcR, suggesting formation of a CD82-FcR multimolecular signaling complex. Antibody cross-linking, calcium imaging (intracellular calcium measurement), tyrosine phosphorylation assay, pharmacological inhibitors (PLC inhibition) Journal of leukocyte biology Medium 7790779

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1997 TRAIL-R2: a novel apoptosis-mediating receptor for TRAIL. The EMBO journal 967 9311998
1995 KAI1, a metastasis suppressor gene for prostate cancer on human chromosome 11p11.2. Science (New York, N.Y.) 720 7754374
2007 PRMT6-mediated methylation of R2 in histone H3 antagonizes H3 K4 trimethylation. Genes & development 242 18079182
1996 KAI1 expression is up-regulated in early pancreatic cancer and decreased in the presence of metastases. Cancer research 159 8895737
2019 R2-P2 rapid-robotic phosphoproteomics enables multidimensional cell signaling studies. Molecular systems biology 150 31885202
1990 Type I (R1) and type II (R2) ribosomal DNA insertions of Drosophila melanogaster are retrotransposable elements closely related to those of Bombyx mori. Journal of molecular biology 134 1690812
1999 Loss of KAI1 expression in the progression of colorectal cancer. Cancer research 123 10582691
1998 The expression of the KAI1 gene, a tumor metastasis suppressor, is directly activated by p53. Proceedings of the National Academy of Sciences of the United States of America 122 9736732
2005 KAI1/CD82, a tumor metastasis suppressor. Cancer letters 118 16260083
2003 Tetraspanin CD82 regulates compartmentalisation and ligand-induced dimerization of EGFR. Journal of cell science 103 14576349
2008 Ganglioside GM2/GM3 complex affixed on silica nanospheres strongly inhibits cell motility through CD82/cMet-mediated pathway. Proceedings of the National Academy of Sciences of the United States of America 93 18272501
2004 The palmitoylation of metastasis suppressor KAI1/CD82 is important for its motility- and invasiveness-inhibitory activity. Cancer research 91 15492270
2003 EWI2/PGRL associates with the metastasis suppressor KAI1/CD82 and inhibits the migration of prostate cancer cells. Cancer research 88 12750295
2004 KAI1 COOH-terminal interacting tetraspanin (KITENIN), a member of the tetraspanin family, interacts with KAI1, a tumor metastasis suppressor, and enhances metastasis of cancer. Cancer research 87 15205336
2015 High nigral iron deposition in LRRK2 and Parkin mutation carriers using R2* relaxometry. Movement disorders : official journal of the Movement Disorder Society 79 26011561
2005 CD82 metastasis suppressor gene: a potential target for new therapeutics? Trends in molecular medicine 79 16271511
2011 Dissecting the diverse functions of the metastasis suppressor CD82/KAI1. FEBS letters 77 21875585
2019 Exosomal protein CD82 as a diagnostic biomarker for precision medicine for breast cancer. Molecular carcinogenesis 76 30604894
2004 Tetraspanin CD82 attenuates cellular morphogenesis through down-regulating integrin alpha6-mediated cell adhesion. The Journal of biological chemistry 73 15557282
2003 Requirement of the p130CAS-Crk coupling for metastasis suppressor KAI1/CD82-mediated inhibition of cell migration. The Journal of biological chemistry 73 12738793
2007 Adenoviral transduction of MRP-1/CD9 and KAI1/CD82 inhibits lymph node metastasis in orthotopic lung cancer model. Cancer research 71 17308116
1993 Sequence relationship of retrotransposable elements R1 and R2 within and between divergent insect species. Molecular biology and evolution 70 8383793
2015 Integration, Regulation, and Long-Term Stability of R2 Retrotransposons. Microbiology spectrum 68 26104703
2008 Michigan molecular interactions r2: from interacting proteins to pathways. Nucleic acids research 68 18978014
1997 Genomic organization of the human KAI1 metastasis-suppressor gene. Genomics 68 9126478
1998 Reduced KAI1 expression in pancreatic cancer is associated with lymph node and distant metastases. International journal of cancer 64 9699525
2020 High G2M Pathway Score Pancreatic Cancer is Associated with Worse Survival, Particularly after Margin-Positive (R1 or R2) Resection. Cancers 61 33036243
2014 The membrane scaffold CD82 regulates cell adhesion by altering α4 integrin stability and molecular density. Molecular biology of the cell 56 24623721
2013 Metastasis suppressor tetraspanin CD82/KAI1 regulates ubiquitylation of epidermal growth factor receptor. The Journal of biological chemistry 54 23897813
2021 Astrocytic IP3Rs: Beyond IP3R2. Frontiers in cellular neuroscience 49 34393726
2006 KAI1/CD82 suppresses tumor invasion by MMP9 inactivation via TIMP1 up-regulation in the H1299 human lung carcinoma cell line. Biochemical and biophysical research communications 49 16488391
2014 CRF-R2 and the heterosynaptic regulation of VTA glutamate during reinstatement of cocaine seeking. The Journal of neuroscience : the official journal of the Society for Neuroscience 47 25080599
2009 KAI-1/CD82, the molecule and clinical implication in cancer and cancer metastasis. Histology and histopathology 47 19224455
2009 CD82 endocytosis and cholesterol-dependent reorganization of tetraspanin webs and lipid rafts. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 46 19497983
2002 Microscopic (R1) and macroscopic (R2) residual disease in patients with resected non-small cell lung cancer. European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery 46 11932154
2003 Metastasis-suppressor KAI1/CD82 induces homotypic aggregation of human prostate cancer cells through Src-dependent pathway. Experimental & molecular medicine 45 12642901
2001 KAI1 metastasis suppressor gene is frequently down-regulated in cervical carcinoma. The American journal of pathology 43 11696423
2008 Transmembrane interactions are needed for KAI1/CD82-mediated suppression of cancer invasion and metastasis. The American journal of pathology 42 19116362
2023 The retrotransposon R2 maintains Drosophila ribosomal DNA repeats. Proceedings of the National Academy of Sciences of the United States of America 41 37252996
2021 KAI1(CD82) is a key molecule to control angiogenesis and switch angiogenic milieu to quiescent state. Journal of hematology & oncology 40 34530889
2002 Rates of R1 and R2 retrotransposition and elimination from the rDNA locus of Drosophila melanogaster. Genetics 40 12399390
2014 ΔNp63α activates CD82 metastasis suppressor to inhibit cancer cell invasion. Cell death & disease 39 24901051
2014 CD82 restrains pathological angiogenesis by altering lipid raft clustering and CD44 trafficking in endothelial cells. Circulation 39 25149363
2003 The metastasis suppressor gene C33/CD82/KAI1 induces apoptosis through reactive oxygen intermediates. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 39 14597553
1999 Frequent loss of KAI1 expression in squamous and lymphoid neoplasms. An immunohistochemical study of archival tissues. The American journal of pathology 39 10362791
1995 CD82, tetra-span-transmembrane protein, is a regulated transducing molecule on U937 monocytic cell line. Journal of leukocyte biology 38 7790779
2016 CD82 suppresses CD44 alternative splicing-dependent melanoma metastasis by mediating U2AF2 ubiquitination and degradation. Oncogene 37 27041584
2015 Tetraspanin CD82: a suppressor of solid tumors and a modulator of membrane heterogeneity. Cancer metastasis reviews 37 26335499
2009 Identifying CD82 (KAI1) as a marker for human chromophobe renal cell carcinoma. Histopathology 37 20002769
2005 HTLV-1 Gag protein associates with CD82 tetraspanin microdomains at the plasma membrane. Virology 37 16325219
2002 High prevalence of decreased expression of KAI1 metastasis suppressor in human oral carcinogenesis. Clinical cancer research : an official journal of the American Association for Cancer Research 37 11895916
2011 CD82 gene suppression in endometrial stromal cells leads to increase of the cell invasiveness in the endometriotic milieu. Journal of molecular endocrinology 36 21685244
2023 Structural RNA components supervise the sequential DNA cleavage in R2 retrotransposon. Cell 35 37301196
2012 Tetraspanin CD82 inhibits protrusion and retraction in cell movement by attenuating the plasma membrane-dependent actin organization. PloS one 35 23251627
1994 Further characterization of CD82/IA4 antigen (type III surface protein): an activation/differentiation marker of mononuclear cells. Cellular immunology 35 7510585
1998 Decreased expression of the metastasis suppressor gene KAI1 in gastric cancer. Cancer letters 34 9719466
2017 The metastasis suppressor CD82/KAI1 inhibits fibronectin adhesion-induced epithelial-to-mesenchymal transition in prostate cancer cells by repressing the associated integrin signaling. Oncotarget 33 27926483
2015 Hepatitis B virus induces RNR-R2 expression via DNA damage response activation. Journal of hepatology 33 26026873
2013 CD82 regulates STAT5/IL-10 and supports survival of acute myelogenous leukemia cells. International journal of cancer 32 23797738
1998 KAI1 is unchanged in metastatic and nonmetastatic esophageal and gastric cancers. Cancer research 32 9485031
2000 Relationship between expression of the KAI1 metastasis suppressor and other markers of advanced bladder cancer. The Journal of pathology 31 10767717
2007 Interaction of Duffy antigen receptor for chemokines and KAI1: a critical step in metastasis suppression. Cancer research 30 17308076
2003 KAI1 metastasis suppressor protein is down-regulated during the progression of human endometrial cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 30 12684410
2022 Conjugation of VEGFR1/R2-targeting peptide with gold nanoparticles to enhance antiangiogenic and antitumoral activity. Journal of nanobiotechnology 29 34983556
2014 Identification of RNA binding motifs in the R2 retrotransposon-encoded reverse transcriptase. Nucleic acids research 28 24957604
2007 Effect of KAI1/CD82 on the beta1 integrin maturation in highly migratory carcinoma cells. Biochemical and biophysical research communications 28 17560548
2019 The metastasis suppressor CD82/KAI1 represses the TGF-β 1 and Wnt signalings inducing epithelial-to-mesenchymal transition linked to invasiveness of prostate cancer cells. The Prostate 27 31212375
2019 Trophoblast-derived CXCL12 promotes CD56bright CD82- CD29+ NK cell enrichment in the decidua. American journal of reproductive immunology (New York, N.Y. : 1989) 27 31650642
2012 KAI1 suppresses HIF-1α and VEGF expression by blocking CDCP1-enhanced Src activation in prostate cancer. BMC cancer 27 22390300
2010 A role for KAI1 in promotion of cell proliferation and mammary gland hyperplasia by the gp78 ubiquitin ligase. The Journal of biological chemistry 27 20089858
2022 Bifidobacterium bifidum H3-R2 and Its Molecular Communication within the Context of Ulcerative Colitis. Journal of agricultural and food chemistry 26 36095239
2020 Repeated introduction and spread of the MRSA clone t304/ST6 in northern Europe. Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases 26 32439595
2017 KAI1/CD82, Metastasis Suppressor Gene as a Therapeutic Target for Non-Small-Cell Lung Carcinoma. Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer 26 29283339
2021 PEDF is an endogenous inhibitor of VEGF-R2 angiogenesis signaling in endothelial cells. Experimental eye research 25 34742690
2021 Role of Metastasis Suppressor KAI1/CD82 in Different Cancers. Journal of oncology 23 34306081
2019 CD82 controls CpG-dependent TLR9 signaling. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 23 31408613
2011 N-Glycosylation pattern of recombinant human CD82 (KAI1), a tumor-associated membrane protein. Journal of proteomics 23 22123080
2003 Chromosomal location of a race-specific resistance gene to Mycosphaerella graminicola in the spring wheat ST6. TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik 22 12898022
1997 Evolution of R1 and R2 in the rDNA units of the genus Drosophila. Genetica 22 9440258
2014 Alternative splicing of KAI1 abrogates its tumor-suppressive effects on integrin αvβ3-mediated ovarian cancer biology. Cellular signalling 21 25435431
2013 Evolution of the R2 retrotransposon ribozyme and its self-cleavage site. PloS one 21 24066021
2009 Effect of expressional alteration of KAI1 on breast cancer cell growth, adhesion, migration and invasion. Cancer genomics & proteomics 21 19656997
2005 Functional expression of TRAIL and TRAIL-R2 during human megakaryocytic development. Journal of cellular physiology 21 15828026
1999 CD82 (KAI1), a member of the tetraspan family, is expressed on early haemopoietic progenitor cells and up-regulated in distinct human leukaemias. British journal of haematology 21 10583248
2020 Population Structure of Non-ST6 Listeria monocytogenes Isolated in the Red Meat and Poultry Value Chain in South Africa. Microorganisms 20 32751410
2011 Detection and characterization of a ST6 clone of vanB2-Enterococcus faecalis from three different hospitals in Spain. European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology 20 21626450
2023 Inhibition of CD82 improves colitis by increasing NLRP3 deubiquitination by BRCC3. Cellular & molecular immunology 19 36600050
2018 Tetraspanin CD82 affects migration, attachment and invasion of rheumatoid arthritis synovial fibroblasts. Annals of the rheumatic diseases 19 29980577
2018 Liprin-α1 modulates cancer cell signaling by transmembrane protein CD82 in adhesive membrane domains linked to cytoskeleton. Cell communication and signaling : CCS 19 30005669
2018 The tetraspanin CD82 regulates bone marrow homing and engraftment of hematopoietic stem and progenitor cells. Molecular biology of the cell 19 30133344
2008 Phorbol ester enhances KAI1 transcription by recruiting Tip60/Pontin complexes. Neoplasia (New York, N.Y.) 19 19048121
2004 Promoter of TRAIL-R2 gene. Vitamins and hormones 19 15110170
2001 KAI1, CAR, and Smad4 expression in the progression of colorectal tumor. Journal of gastroenterology 19 11480790
1997 Cloning, sequencing and expression of ribonucleotide reductase R2 from Trypanosoma brucei. FEBS letters 19 9315738
2020 MicroRNA-633 enhances melanoma cell proliferation and migration by suppressing KAI1. Oncology letters 18 33376521
2012 Expression of CD82 in human trophoblast and its role in trophoblast invasion. PloS one 18 22679510
2006 Characterization of an antibody that can detect the Kai1/CD82 murine metastasis suppressor. The Prostate 18 16372335
2021 Neurochemically and Hodologically Distinct Ascending VGLUT3 versus Serotonin Subsystems Comprise the r2-Pet1 Median Raphe. The Journal of neuroscience : the official journal of the Society for Neuroscience 17 33547164
2020 CD82 Suppresses ADAM17-Dependent E-Cadherin Cleavage and Cell Migration in Prostate Cancer. Disease markers 17 33204367
2012 Regulation of estradiol and progesterone production by CRH-R1 and -R2 is through divergent signaling pathways in cultured human placental trophoblasts. Endocrinology 17 22865371