Affinage

Showing CD82 — KAI1 is a alias.

CD82

CD82 antigen · UniProt P27701

Length
267 aa
Mass
29.6 kDa
Annotated
2026-06-09
100 papers in source corpus 37 papers cited in narrative 37 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CD82/KAI1 is a tetraspanin scaffold protein that organizes membrane microdomains to suppress tumor metastasis and to regulate cell migration, hematopoietic stem cell behavior, and innate immune signaling (PMID:7754374, PMID:15492270). First identified as a metastasis suppressor that blocks dissemination of prostate cancer cells in vivo (PMID:7754374), CD82 functions by physically reorganizing the plasma membrane: its palmitoylation at juxtamembrane cysteines and its transmembrane polar residues are required for incorporation into tetraspanin-enriched microdomains, association with tetraspanins CD9 and CD151, and the downstream control of migration and invasion (PMID:15492270, PMID:19116362). CD82 attenuates promigratory signaling on multiple fronts — it inhibits integrin–c-Met crosstalk and Src/FAK/p130CAS-CrkII coupling (PMID:16331263, PMID:12738793), dampens Rac1 and RhoA activity to block lamellipodia and stress-fiber formation (PMID:23251627), and compartmentalizes EGFR into ganglioside-rich domains while limiting its ligand-induced dimerization and promoting c-Cbl–dependent receptor downregulation (PMID:14576349, PMID:23897813). It restrains invasion further by upregulating TIMP1 to inactivate MMP-9 (PMID:16488391) and by binding and inhibiting the sheddase ADAM17 (PMID:33204367). CD82 engages a broad partner set through its large extracellular loop and membrane scaffolding, including EWI2/PGRL, TIMP-1, and the endothelial receptor DARC, the last of which mediates CD82-dependent induction of senescence via TBX2/p21 and is essential for metastasis suppression in vivo (PMID:16862154, PMID:12750295, PMID:28030805). Beyond cancer, CD82–DARC interaction on bone marrow macrophages stabilizes CD82 on hematopoietic stem cells to maintain quiescence through TGF-β1/Smad3-driven CDK-inhibitor expression, while CD82 loss causes Rac1 hyperactivation and impaired HSPC homing (PMID:26996598, PMID:30133344). In innate immunity, CD82 controls TLR9 trafficking and myddosome assembly to drive NF-κB signaling (PMID:31408613), and it restrains NLRP3 inflammasome activation by binding NLRP3 and the deubiquitinase BRCC3 (PMID:36600050). Transcriptionally, CD82 is a direct target of the p53-family factors ΔNp63α and TAp73, through which these tumor suppressors enforce their anti-invasive programs (PMID:24901051, PMID:29222041).

Mechanistic history

Synthesis pass · year-by-year structured walk · 24 steps
  1. 1995 High

    Established CD82 as a bona fide metastasis suppressor gene and defined its tetraspanin architecture, framing all subsequent mechanistic work.

    Evidence Molecular cloning plus gene transfection into rat prostate cancer cells with in vivo metastasis assay

    PMID:7754374

    Open questions at the time
    • Did not define the molecular partners or signaling pathways through which suppression occurs
    • Mechanism of membrane organization not addressed
  2. 2003 Medium

    Connected CD82 to motility machinery by showing it downregulates p130CAS to break the p130CAS-CrkII motility switch, defining a concrete cytoskeletal output.

    Evidence KAI1 expression in Du145 cells with migration assays, Co-IP, and p130CAS overexpression rescue

    PMID:12738793

    Open questions at the time
    • How CD82 lowers p130CAS protein levels not established
    • Link to upstream membrane scaffolding not yet made
  3. 2003 Medium

    Identified EWI2/PGRL as a direct, raft-independent CD82 partner that synergizes in migration inhibition, expanding the CD82 interactome beyond classical tetraspanins.

    Evidence Co-IP, cross-linking, mass spectrometry, and migration assays in prostate cancer cells

    PMID:12750295

    Open questions at the time
    • Functional consequence of the complex at the signaling level not defined
    • Stoichiometry in vivo unknown
  4. 2003 Medium

    Showed CD82 attenuates EGFR specifically by relocating it into ganglioside-rich membrane fractions, introducing the microdomain-compartmentalization model of receptor regulation.

    Evidence Sucrose gradient fractionation, dimerization assays, and ganglioside redistribution analysis

    PMID:14576349

    Open questions at the time
    • Selectivity for EGFR over ErbB2/3 mechanistically unexplained
    • Direct CD82-EGFR contact not demonstrated
  5. 2004 High

    Demonstrated palmitoylation is required for CD82 microdomain association and all downstream motility-suppressing functions, identifying the lipid modification as the master switch for CD82 activity.

    Evidence Palmitoylation-deficient mutant with migration/invasion, tetraspanin Co-IP, and actin imaging

    PMID:15492270

    Open questions at the time
    • Palmitoyltransferase responsible not identified in this work
    • Dynamics of palmitoylation cycling unaddressed
  6. 2006 High

    Defined CD82 inhibition of integrin–c-Met crosstalk and Src signaling, linking membrane scaffolding to receptor tyrosine kinase suppression.

    Evidence CD82 re-expression in PC3 cells with integrin-dependent signaling and invasion assays

    PMID:16331263

    Open questions at the time
    • Whether CD82 directly contacts c-Met or integrins not shown
    • Relative contribution of each kinase node unresolved
  7. 2006 High

    Discovered the DARC interaction as the in vivo effector of metastasis suppression, linking tumor-cell CD82 to endothelial-induced senescence via TBX2/p21.

    Evidence Yeast two-hybrid screen, DARC-knockout mouse metastasis assays, and senescence assays

    PMID:16862154

    Open questions at the time
    • How DARC engagement triggers TBX2/p21 intracellularly not defined
    • Signal transduction from cell surface to nucleus unmapped
  8. 2006 Medium

    Added an extracellular-matrix arm by showing CD82 upregulates TIMP1 to inactivate MMP-9, explaining anti-invasive activity independent of motility signaling.

    Evidence CD82 transfection in H1299 cells with invasion assays and gelatin zymography

    PMID:16488391

    Open questions at the time
    • Mechanism of TIMP1 upregulation by CD82 unknown
    • Single cell line tested
  9. 2009 Medium

    Established that CD82 traffics by cholesterol-dependent endocytosis to late endosomes/lysosomes and reorganizes microdomain cholesterol, framing CD82 function as regulated by its own membrane turnover.

    Evidence Endocytosis assays with inhibitors, cholesterol depletion, and fractionation

    PMID:19497983

    Open questions at the time
    • Trigger for CD82 internalization not defined
    • Functional link between endocytosis and migration relief only correlative
  10. 2009 Medium

    Mapped TM polar residues as required for CD82 conformation and tetraspanin partnerships underlying metastasis suppression, complementing palmitoylation as a structural determinant.

    Evidence TM polar residue mutagenesis with metastasis, Co-IP, and structural modeling

    PMID:19116362

    Open questions at the time
    • No experimental structure of CD82 TM bundle
    • Single-lab functional readouts
  11. 2010 Medium

    Identified TI-VAMP/VAMP7 as the trafficking machinery delivering CD82 from Golgi to the surface, where CD82 then controls EGFR diffusion and endocytic fate.

    Evidence TI-VAMP and CD82 siRNA with quantum-dot EGFR tracking and MAPK assays

    PMID:20144992

    Open questions at the time
    • Whether VAMP7 selectively sorts CD82 versus bulk cargo unclear
    • Direct VAMP7-CD82 interaction not shown
  12. 2012 Medium

    Resolved CD82 control of actin dynamics by showing it suppresses both Rac1 (protrusion) and RhoA (retraction) activity and lowers peripheral PIP2.

    Evidence Live imaging with Rac1/RhoA/ROCK activity assays and PIP2 staining

    PMID:23251627

    Open questions at the time
    • Upstream GEF/GAP targets of CD82 not identified
    • Mechanism linking microdomains to GTPase regulation unmapped
  13. 2013 Medium

    Refined EGFR regulation by showing CD82 suppresses EGFR ubiquitylation via PKC-dependent c-Cbl phosphorylation and EGFR T654 phosphorylation, requiring the CD82 cytoplasmic tail.

    Evidence Ubiquitylation and c-Cbl phosphorylation assays with CD82ΔC mutant

    PMID:23897813

    Open questions at the time
    • How the cytoplasmic tail recruits PKC not defined
    • Reconciliation with EGFR compartmentalization model incomplete
  14. 2014 Medium

    Demonstrated with superresolution imaging that CD82 increases α4 integrin clustering density to promote adhesion, dependent on palmitoylation, giving a direct structural readout of microdomain organization.

    Evidence dSTORM superresolution imaging with clustering analysis and palmitoylation mutant

    PMID:24623721

    Open questions at the time
    • Whether CD82 directly contacts α4 integrin unresolved
    • Single integrin subunit examined
  15. 2014 Medium

    Placed CD82 downstream of ΔNp63α as a direct transcriptional target required for that factor's anti-invasive program.

    Evidence ChIP, gain/loss-of-function, and Matrigel outgrowth rescue assays

    PMID:24901051

    Open questions at the time
    • Generality of the ΔNp63α-CD82 axis across tumor types untested
    • Other ΔNp63α targets contributing to phenotype not excluded
  16. 2016 High

    Extended the DARC axis to hematopoiesis, showing macrophage DARC stabilizes CD82 on HSCs to enforce quiescence via TGF-β1/Smad3 CDK inhibitors.

    Evidence Cd82-/- mouse, macrophage ablation, and TGF-β1/Smad3 signaling/cell cycle assays

    PMID:26996598

    Open questions at the time
    • How CD82 transduces DARC engagement into TGF-β1 signaling unmapped
    • Direct CD82-Smad linkage not established
  17. 2017 Medium

    Identified CD82 as a direct TAp73 transcriptional target essential for TAp73-driven suppression of colorectal cancer invasion and metastasis.

    Evidence Luciferase reporter, ChIP, epistasis rescue, and in vivo hepatic metastasis model

    PMID:29222041

    Open questions at the time
    • Overlap with ΔNp63α regulation of the same promoter not dissected
    • Tissue specificity of the axis unclear
  18. 2017 Medium

    Defined a direct CD82–TIMP-1 interaction through the large extracellular loop that drives TIMP-1 endocytosis and its anti-migratory effect.

    Evidence Co-IP, co-localization in cells and clinical samples, and TIMP-1 endocytosis/migration assays

    PMID:28030805

    Open questions at the time
    • Structural basis of the extracellular-loop interaction unknown
    • Relationship to CD82-driven TIMP1 upregulation unresolved
  19. 2018 Medium

    Showed CD82 loss causes Rac1 hyperactivation and defective HSPC bone marrow homing, mechanistically tying CD82 GTPase control to stem-cell trafficking.

    Evidence CD82-knockout mouse with in vivo homing assay and Rac1-inhibitor rescue

    PMID:30133344

    Open questions at the time
    • How CD82 restrains Rac1 in HSPCs mechanistically unclear
    • Adhesion versus migration contributions not separated
  20. 2018 Medium

    Revealed a pathogen-co-opted CD82 function: M. tuberculosis induces CD82 to arrest phagosome maturation via a CD82-RUNX1-Rab5/22 axis promoting bacterial survival.

    Evidence CD82 promoter methylation analysis, KO/knockdown macrophages, Rab interaction and phagosome maturation assays, in vivo infection

    PMID:29760437

    Open questions at the time
    • How CD82 engages RUNX1 and Rab GTPases molecularly undefined
    • Whether this reflects normal CD82 endosomal function unclear
  21. 2019 Medium

    Established CD82 as a positive regulator of TLR9 trafficking and myddosome assembly, broadening CD82 into innate immune receptor handling.

    Evidence Co-IP of CD82-TLR9, myddosome formation and NF-κB assays in CD82-deficient macrophages

    PMID:31408613

    Open questions at the time
    • Direct versus indirect CD82-TLR9 association not resolved
    • Step in TLR9 trafficking controlled by CD82 not pinpointed
  22. 2019 Medium

    Showed CD82 blocks TGF-β1- and Wnt-driven EMT in prostate cancer by inhibiting Smad and β-catenin nuclear signaling, linking metastasis suppression to EMT control.

    Evidence Reporter assays, Smad4/β-catenin localization, GSK-3β analysis, and invasion assays

    PMID:31212375

    Open questions at the time
    • Reconciliation with HSC TGF-β1/Smad3 promotion versus tumor TGF-β1/Smad inhibition unaddressed
    • Direct CD82 effector on these pathways unknown
  23. 2021 Medium

    Identified zDHHC4 as the palmitoyltransferase for CD82 in pericytes and showed CD82 directly binds VEGF/PDGF and induces LIF to suppress angiogenesis.

    Evidence KAI1-knockout mice, palmitoylation assay identifying zDHHC4, VEGF/PDGF binding, and in vivo supplementation

    PMID:34530889

    Open questions at the time
    • Whether zDHHC4 modifies CD82 in other cell types untested
    • Stoichiometry of CD82-VEGF/PDGF binding unknown
  24. 2023 Medium

    Defined a CD82 inflammasome-restraining function by showing CD82 binds NLRP3 and BRCC3 to block deubiquitination and promote NLRP3 degradation.

    Evidence Co-IP of CD82-NLRP3 and CD82-BRCC3, K63 ubiquitination assays, and KO colitis model

    PMID:36600050

    Open questions at the time
    • Whether CD82 acts at the membrane or in cytosol for this function unclear
    • Structural basis of CD82-BRCC3 interaction unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single tetraspanin scaffold integrates its contradictory context-dependent roles — suppressing TGF-β1/Smad signaling in tumor cells yet promoting it in HSCs, and acting at the plasma membrane versus endosomes versus the nucleus-adjacent transcriptional axes — remains unresolved.
  • No structural model unifying palmitoylation, TM packing, and partner selection
  • Mechanism of signal transduction from CD82 surface engagement to intracellular outputs largely undefined
  • Cell-type determinants of opposing CD82 outputs not identified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 5 GO:0060090 molecular adaptor activity 4 GO:0098631 cell adhesion mediator activity 2
Localization
GO:0005768 endosome 4 GO:0005886 plasma membrane 4 GO:0005783 endoplasmic reticulum 1 GO:0005794 Golgi apparatus 1
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-1474244 Extracellular matrix organization 3 R-HSA-1643685 Disease 3 R-HSA-168256 Immune System 3
Partners
ADAM17BRCC3CD151DARCEWI2NLRP3TIMP1TLR9
Complex memberships
tetraspanin-enriched microdomain

Evidence

Reading pass · 37 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 KAI1/CD82 encodes a 267-amino acid tetraspanin protein with four hydrophobic transmembrane domains and one large extracellular hydrophilic domain with three potential N-glycosylation sites; its introduction into rat AT6.1 prostate cancer cells suppressed metastasis, establishing it as a metastasis suppressor gene. Gene transfection into rat prostate cancer cells with in vivo metastasis assay; molecular cloning and sequence analysis Science High 7754374
2006 KAI1/CD82 on tumor cells directly interacts with DARC (gp-Fy/CD234) on vascular endothelial cells; this interaction inhibits tumor cell proliferation and induces senescence by modulating TBX2 and p21 expression, and is essential for metastasis suppression in vivo. Yeast two-hybrid screen to identify DARC as KAI1 binding partner; DARC knockout mouse metastasis assays; cell proliferation and senescence assays Nature medicine High 16862154
2016 CD82/KAI1 on long-term hematopoietic stem cells (LT-HSCs) interacts with DARC expressed on bone marrow macrophages, stabilizing CD82 on LT-HSCs and maintaining their quiescence through TGF-β1/Smad3-mediated induction of CDK inhibitors; ablation of DARC+ macrophages reduces surface CD82 and causes LT-HSC cell-cycle entry and differentiation. Cd82−/− mouse model; macrophage ablation experiments; TGF-β1/Smad3 signaling assays; cell cycle analysis Cell stem cell High 26996598
2006 CD82/KAI1 suppresses invasion by inhibiting integrin-dependent crosstalk with c-Met receptor and Src kinases; restoration of CD82 in PC3 prostate cancer cells reduced integrin-induced activation of c-Met (including HGF/SF-stimulated activation), Src kinase phosphorylation, and downstream substrates p130Cas and FAK Y861. CD82 re-expression in metastatic PC3 cells; integrin-dependent signaling assays; c-Met inhibition; Src kinase inhibition; Matrigel invasion assay Oncogene High 16331263
2003 CD82 specifically attenuates ligand-induced dimerization of EGFR but not ErbB2-ErbB3 complexes; CD82 causes redistribution of EGFR into cholesterol/ganglioside-rich light membrane fractions and increases surface expression of gangliosides GD1a and GM1, with GD1a mediating CD82-dependent compartmentalization of EGFR and thereby attenuating EGF signaling. Sucrose gradient fractionation; dimerization assays; ganglioside redistribution analysis; soluble CD82 large extracellular loop recombinant protein experiments Journal of cell science Medium 14576349
2013 CD82/KAI1 specifically suppresses ubiquitylation of EGFR after stimulation with heparin-binding EGF or amphiregulin, dependent on the heparin-binding domain of the ligand; CD82 acts by promoting PKC-dependent serine phosphorylation of c-Cbl (the E3 ubiquitin ligase for EGFR), and increases phosphorylation of threonine 654 in the EGFR juxtamembrane domain; deletion of the CD82 C-terminal cytoplasmic domain disrupts this activity. Ubiquitylation assays; c-Cbl phosphorylation assays; CD82 deletion mutant (CD82ΔC); EEA1-positive endosome trafficking assays; endocytic trafficking experiments The Journal of biological chemistry Medium 23897813
2003 KAI1/CD82 expression decreases p130CAS protein levels in metastatic prostate cancer cells, thereby reducing formation of the p130CAS-CrkII complex ('molecular switch' for cell motility); overexpression of p130CAS in CD82-expressing cells rescues migration, confirming that p130CAS-CrkII coupling is required for KAI1/CD82-mediated inhibition of cell motility. KAI1 expression in Du145 cells; migration assays; Western blot for FAK, Lyn, p130CAS; Co-IP for p130CAS-CrkII complex; p130CAS overexpression rescue The Journal of biological chemistry Medium 12738793
2003 EWI2/PGRL (an immunoglobulin superfamily member) directly and stoichiometrically associates with KAI1/CD82, independent of cholesterol-enriched lipid rafts and independent of CD81 and CD9; EWI2/PGRL overexpression inhibits prostate cancer cell migration and synergizes with KAI1/CD82 in migration inhibition. Co-immunoprecipitation; chemical cross-linking; sucrose gradient fractionation; peptide mass spectrometry identification; migration assays on fibronectin and laminin Cancer research Medium 12750295
2004 KAI1/CD82 is palmitoylated at cytoplasmic cysteine residues proximal to the plasma membrane; palmitoylation is required for CD82's inhibitory effects on migration and invasion, its subcellular distribution, its association with tetraspanin-enriched microdomains, lamellipodia formation, actin cytoskeleton organization, and the p130CAS-CrkII coupling that mediates motility inhibition. Palmitoylation assay; palmitoylation-deficient CD82 mutant; migration/invasion assays; tetraspanin co-immunoprecipitation; actin cytoskeleton imaging Cancer research High 15492270
2008 KAI1/CD82 transmembrane polar residues (Asn, Gln, Glu) mediate TM-domain interactions required for migration, invasion, and metastasis suppression; mutation of all three polar residues disrupts KAI1/CD82's interactions with tetraspanins CD9 and CD151 (but not with α3β1 integrin), inhibits formation of microprotrusions and microvesicle release, and destabilizes CD82 conformation. TM polar residue mutagenesis; metastasis assay; Co-IP with CD9 and CD151; migration/invasion assays; microprotrusion and microvesicle release assays; denaturation sensitivity assay; structural modeling The American journal of pathology Medium 19116362
2009 CD82 undergoes cholesterol/lipid-dependent endocytosis (not requiring dynamin or clathrin) and traffics to late endosomes and lysosomes; CD82 redistributes cholesterol into tetraspanin-enriched microdomains (TEMs), reorganizing TEMs and lipid rafts; CD82 endocytosis appears to alleviate CD82-mediated inhibition of cell migration. Endocytosis assays with dynamin and clathrin inhibitors; cholesterol depletion/sequestration; sucrose gradient fractionation; co-localization imaging FASEB journal Medium 19497983
2010 TI-VAMP (VAMP7) transports CD82 from the Golgi apparatus to the cell surface; depletion of TI-VAMP reduces surface CD82 levels, restrains EGFR diffusion at the cell surface, impairs MAPK signaling, and enhances clathrin-dependent endocytosis of activated EGFR via increased AP-2 recruitment. TI-VAMP siRNA depletion; CD82 siRNA; quantum dots video-microscopy of EGFR dynamics; MAPK signaling assays; AP-2 recruitment assays; Golgi secretion assays Journal of cell science Medium 20144992
2006 KAI1/CD82 suppresses tumor invasion by upregulating TIMP1, which inactivates MMP-9 activity; CD82-transfected H1299 lung carcinoma cells showed reduced invasion, reduced MMP-9 enzyme activity (despite elevated MMP-9 mRNA and protein), and elevated TIMP1 levels. CD82 transfection; cell invasion assay; gelatin zymography for MMP-9 activity; Western blot and RT-PCR Biochemical and biophysical research communications Medium 16488391
2003 C33/CD82/KAI1 induces apoptosis through generation of reactive oxygen intermediates (ROIs); this is not derived from the mitochondrial respiratory chain but involves CD82-induced release of intracellular glutathione (GSH) and activation of GTPase Cdc42, which mediates GSH release and apoptosis induction. Apoptosis screen; cell death assays; ROI measurement; GSH release assay; Cdc42 activation assay FASEB journal Medium 14597553
2012 KAI1/CD82 inhibits polarized protrusion and retraction events in migrating cells by disrupting actin reorganization; specifically, CD82 reduces Rac1 activity (diminishing lamellipodia and actin cortical network) and blocks growth factor-stimulated RhoA activity (suppressing stress fibers and retraction), and reduces PIP2 at the cell periphery. Live imaging of CD82-expressing cells; Rac1 and RhoA GTPase activity assays; ROCK activity assay; cofilin localization imaging; PIP2 staining PloS one Medium 23251627
2014 CD82 overexpression increases the molecular density of α4 integrin subunits within membrane clusters, thereby increasing cellular adhesion; this clustering depends on CD82 palmitoylation and the presence of α4 integrin ligands. Direct stochastic optical reconstruction microscopy (dSTORM) superresolution imaging; protein clustering algorithms; palmitoylation mutant of CD82; adhesion assays Molecular biology of the cell Medium 24623721
2018 CD82 deficiency disrupts bone marrow homing and engraftment of HSPCs; this homing defect is due at least in part to hyperactivation of Rac1, as pharmacological Rac1 inhibition rescues homing capacity of CD82-knockout HSPCs. CD82 knockout mouse model; in vivo HSPC homing assay; Rac1 inhibitor rescue experiment; migration and cell spreading assays Molecular biology of the cell Medium 30133344
2019 CD82/KAI1 inhibits TGF-β1- and Wnt-induced epithelial-to-mesenchymal transition (EMT) in prostate cancer cells; high CD82 expression prevents phosphorylation of Smad2, nuclear translocation of Smad4, and TRE promoter transactivation downstream of TGF-β1; it also maintains GSK-3β activity to phosphorylate β-catenin, preventing Wnt/β-catenin nuclear signaling. Luciferase reporter assay for TRE and Tcf/Lef promoters; immunofluorescence and subcellular fractionation for Smad4 and β-catenin localization; invasion assays; GSK-3β phosphorylation analysis The Prostate Medium 31212375
2019 CD82 is a key regulator of TLR9 trafficking and signaling; CD82 associates with TLR9 in macrophages (in the ER and post-ER compartments), is essential for TLR9-dependent myddosome formation in response to CpG stimulation, and modulates TLR9-dependent NF-κB nuclear translocation and inflammatory cytokine production. Co-immunoprecipitation of CD82 and TLR9; myddosome formation assay; NF-κB nuclear translocation assay; CD82-deficient cells; CpG stimulation experiments FASEB journal Medium 31408613
2018 Virulent M. tuberculosis induces CD82 promoter hypomethylation, leading to CD82 expression in macrophages; CD82 targets RUNX1 and this CD82-RUNX1 axis arrests phagosome maturation via interaction with Rab5/Rab22, promoting intracellular mycobacterial survival; knockdown or knockout of CD82 or RUNX1 increased phagolysosome biogenesis and antimicrobial activity. CD82 promoter methylation analysis; CD82 KO/knockdown in macrophages; RUNX1 targeting; Rab5/Rab22 interaction assays; phagosome maturation assay; in vivo MTB infection model Experimental & molecular medicine Medium 29760437
2011 N-glycosylation of recombinant human CD82 occurs at three sites including a previously unreported site at Asn157; the glycans include bisecting N-acetylglucosamine, (α-2,6) N-acetylneuraminic acid, and core fucose epitopes, which are associated with cell adhesion and cancer metastasis functions. Glycosidase and protease digestions; glycan permethylation; mass spectrometry; site-directed mutagenesis; lectin blots Journal of proteomics Medium 22123080
2013 CD82 positively regulates the STAT5/IL-10 signaling pathway in acute myelogenous leukemia (AML) stem cells; CD82 knockdown dephosphorylates STAT5 and reduces IL-10 levels, while forced CD82 expression increases p-STAT5 and IL-10; STAT5A binds the IL-10 gene promoter as shown by ChIP assay. shRNA knockdown; lentiviral CD82 overexpression; Western blot for p-STAT5; ELISA for IL-10; chromatin immunoprecipitation (ChIP); luciferase reporter assay; in vivo mouse model International journal of cancer Medium 23797738
2016 CD82 regulates PKCα-mediated signaling in AML cells; using a palmitoylation-deficient CD82 mutant (which disrupts membrane organization), CD82 was shown to control PKCα expression and membrane activation, stabilize PKCα activation at the membrane, regulate the size of PKCα membrane clusters, and produce sustained ERK1/2 activation resulting in enhanced AML colony formation. Palmitoylation mutant CD82; single-molecule and ensemble imaging (TIRF, confocal); PKCα membrane cluster analysis; ERK1/2 phosphorylation assays; colony formation assay Scientific reports Medium 27417454
2021 KAI1/CD82 expressed in pericytes localizes to the membrane surface after palmitoylation by zDHHC4 enzyme and induces LIF expression through the Src/p53 pathway; LIF released from pericytes suppresses angiogenic factors in endothelial cells; additionally, KAI1 directly binds VEGF and PDGF and inhibits activation of their receptors. KAI1 knockout mice (enhanced angiogenesis phenotype); palmitoylation assay identifying zDHHC4; Src/p53 pathway analysis; VEGF/PDGF direct binding assays; in vivo cancer models with KAI1 supplementation; KAI1 large extracellular loop peptide in vivo Journal of hematology & oncology Medium 34530889
2020 CD82 overexpression increases TRPM7 α-kinase cleavage via caspase-3 activation and induces Numb phosphorylation at Thr346 and Ser348; CD82 overexpression promotes beta-amyloid peptide (Aβ) secretion, reversible by Numb T346S348 mutants; hippocampus-related memory functions are improved in Cd82−/− mice. AAV-CD82 hippocampal injection; TRPM7 cleavage assays; caspase-3 activation; Numb phosphorylation at specific residues; Numb phospho-mutant rescue; Aβ secretion measurement; Cd82−/− behavioral testing GeroScience Medium 32088828
2023 CD82 suppresses NLRP3 inflammasome activation by binding both NLRP3 and BRCC3 (a K63-specific deubiquitinase); CD82 binding to BRCC3 blocks BRCC3-dependent K63-specific deubiquitination of NLRP3, leading to increased NLRP3 degradation. Co-immunoprecipitation identifying CD82-NLRP3 and CD82-BRCC3 complexes; K63 ubiquitination assays; CD82 KO mouse colitis model; in vitro NLRP3 inflammasome activation assays Cellular & molecular immunology Medium 36600050
2014 ΔNp63α directly activates CD82 transcription as shown by chromatin immunoprecipitation; CD82 is required for ΔNp63α-mediated inhibition of cell invasion, as CD82 ablation reverses the anti-invasive effect and ectopic CD82 rescues invasion upon ΔNp63α knockdown; GSK3β inhibition downregulates both ΔNp63α and CD82 and increases invasion independently of β-catenin. Affymetrix gene expression profiling; gain- and loss-of-function analysis; chromatin immunoprecipitation (ChIP); Matrigel outgrowth assay; siRNA knockdown; GSK3β pharmacological inhibition and siRNA Cell death & disease Medium 24901051
2017 TAp73 directly activates KAI1/CD82 transcription; KAI1 expression is indispensable for TAp73-mediated inhibition of colorectal cancer cell invasion and migration; induction of TAp73 elevated KAI1 expression and decreased hepatic metastasis in vivo, while TAp73-mediated anti-invasive effects were abrogated by KAI1 knockdown. Luciferase reporter assay; ChIP; TAp73 induction/knockdown; KAI1 knockdown; invasion/migration assays; in vivo hepatic metastasis model Cancer letters Medium 29222041
2017 CD82 directly binds to TIMP-1 through its large extracellular loop and co-localizes with TIMP-1; CD82 facilitates membrane-bound TIMP-1 endocytosis, which contributes to TIMP-1's anti-migration effect; CD82 silencing partially eliminates TIMP-1-mediated anti-migration activity. Co-immunoprecipitation; co-localization assays in cancer cell lines and clinical samples; CD82 siRNA knockdown; TIMP-1 endocytosis assays; migration assays Oncotarget Medium 28030805
2020 CD82 interacts with ADAM17 and inhibits its metalloprotease activity, thereby suppressing ADAM17-mediated cleavage/shedding of E-cadherin from the cell membrane in prostate cancer cells, and reducing cell migration. Co-immunoprecipitation of CD82 and ADAM17; ADAM17 metalloprotease activity assay; E-cadherin shedding assay; cell migration assay Disease markers Medium 33204367
2012 CD82 inhibits trophoblast invasion and migration by reducing MMP-9 gelatinolytic activity; CD82 siRNA knockdown in trophoblast cells promoted invasion, migration, and MMP-9 activity, while CD82 overexpression decreased invasion, migration, and MMP-9 activity. CD82 siRNA and overexpression in HTR8/SVneo cells; villous explant culture on Matrigel; invasion/migration assays; gelatin zymography for MMP-9 activity PloS one Low 22679510
2009 KAI1/CD82 decreases Rac1 protein expression (but not mRNA) and GTPase activity through the PI3K/Akt/mTOR pathway in lung carcinoma cells; CD82-expressing cells showed lower mTOR expression, suggesting mTOR regulates Rac1 protein translation. Rac1 GTPase activity assay; RT-PCR for Rac1 mRNA; mTOR expression analysis; cell morphology and migration assays Cell biochemistry and function Low 19107873
2012 KAI1/CD82 suppresses HIF-1α and VEGF expression in prostate cancer cells by blocking CDCP1-enhanced Src activation, leading to increased VHL protein levels that promote HIF-1α degradation; this mechanism was validated in vivo in xenograft tumors. KAI1 stable transfection in PC3 cells; Western blot for HIF-1α, VEGF, CDCP1, Src phosphorylation, VHL; VEGF reporter assay; in vivo xenograft; immunohistochemistry BMC cancer Low 22390300
2003 KAI1/CD82 induces homotypic cell aggregation in prostate cancer cells through a Src family kinase-dependent pathway; anti-CD82 antibody ligation increases endogenous Src kinase activity, and kinase-negative Src mutant expression abolishes CD82-mediated homotypic aggregation. KAI1 cDNA transfection in DU145 cells; aggregation assay; Src kinase inhibitor (PP1); Src kinase activity assay; kinase-negative Src mutant transfection Experimental & molecular medicine Low 12642901
1995 Cross-linking of CD82 (IA4) on U937 monocytic cells induces a PLC-dependent increase in intracellular calcium (via IP3) followed by extracellular calcium entry, and causes tyrosine phosphorylation of various proteins; this transducing signal requires dual engagement of both CD82 and Fc receptors. Cross-linking with anti-CD82 antibody; intracellular calcium measurement; phospholipase C inhibitor; tyrosine phosphorylation assay; Fc receptor co-engagement experiments Journal of leukocyte biology Low 7790779
2015 CD82 enhances expression of miR-203, which directly downregulates FZD2 mRNA and protein expression, thereby inhibiting canonical Wnt signaling and cell migration. miRNA expression profiling after CD82 expression; miR-203 mimic/inhibitor transfection; luciferase reporter assay for FZD2 3'UTR targeting; migration assay PloS one Low 26132195
2007 KAI1/CD82 attenuates the maturation of β1 integrin precursor to its functional mature form at the cell surface in lung carcinoma cells, thereby suppressing cell migration; this was confirmed by CD82-specific siRNA knockdown reversing the effect. Western blot for mature vs. precursor β1 integrin; biotinylation assay for surface β1 integrin; wound-healing and Boyden chamber migration assays; CD82 siRNA Biochemical and biophysical research communications Low 17560548

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 969 9311998
1995 KAI1, a metastasis suppressor gene for prostate cancer on human chromosome 11p11.2. Science (New York, N.Y.) 721 7754374
2006 Interaction of KAI1 on tumor cells with DARC on vascular endothelium leads to metastasis suppression. Nature medicine 185 16862154
1998 Correlation of reduction in MRP-1/CD9 and KAI1/CD82 expression with recurrences in breast cancer patients. The American journal of pathology 162 9736046
2019 R2-P2 rapid-robotic phosphoproteomics enables multidimensional cell signaling studies. Molecular systems biology 154 31885202
2016 CD82/KAI1 Maintains the Dormancy of Long-Term Hematopoietic Stem Cells through Interaction with DARC-Expressing Macrophages. Cell stem cell 135 26996598
2006 Tetraspanin KAI1/CD82 suppresses invasion by inhibiting integrin-dependent crosstalk with c-Met receptor and Src kinases. Oncogene 129 16331263
2005 KAI1/CD82, a tumor metastasis suppressor. Cancer letters 119 16260083
2003 Tetraspanin CD82 regulates compartmentalisation and ligand-induced dimerization of EGFR. Journal of cell science 105 14576349
1999 Motility-related protein (MRP-1/CD9) and KAI1/CD82 expression inversely correlate with lymph node metastasis in oesophageal squamous cell carcinoma. British journal of cancer 94 10098753
2004 The palmitoylation of metastasis suppressor KAI1/CD82 is important for its motility- and invasiveness-inhibitory activity. Cancer research 92 15492270
2003 EWI2/PGRL associates with the metastasis suppressor KAI1/CD82 and inhibits the migration of prostate cancer cells. Cancer research 88 12750295
2008 Controlling cell surface dynamics and signaling: how CD82/KAI1 suppresses metastasis. Cellular signalling 84 18822372
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
2000 Mutation and expression of the metastasis suppressor gene KAI1 in esophageal squamous cell carcinoma. Cancer 75 10964324
1996 Expression of the KAI1 protein in benign prostatic hyperplasia and prostate cancer. The American journal of pathology 74 8909232
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
2015 Integration, Regulation, and Long-Term Stability of R2 Retrotransposons. Microbiology spectrum 69 26104703
1998 Frequent downregulation of the KAI1(CD82) metastasis suppressor protein in human cancer cell lines. Oncogene 69 9671393
2010 Role of TI-VAMP and CD82 in EGFR cell-surface dynamics and signaling. Journal of cell science 60 20144992
2005 KAI1 promoter activity is dependent on p53, junB and AP2: evidence for a possible mechanism underlying loss of KAI1 expression in cancer cells. Oncogene 60 15580298
2009 Spleen R2 and R2* in iron-overloaded patients with sickle cell disease and thalassemia major. Journal of magnetic resonance imaging : JMRI 59 19161188
2014 The membrane scaffold CD82 regulates cell adhesion by altering α4 integrin stability and molecular density. Molecular biology of the cell 57 24623721
2013 Metastasis suppressor tetraspanin CD82/KAI1 regulates ubiquitylation of epidermal growth factor receptor. The Journal of biological chemistry 56 23897813
2021 Astrocytic IP3Rs: Beyond IP3R2. Frontiers in cellular neuroscience 50 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
2018 Structure and Analysis of R1 and R2 Pyocin Receptor-Binding Fibers. Viruses 48 30110933
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 47 19497983
2005 KAI1 tetraspanin and metastasis suppressor. The international journal of biochemistry & cell biology 47 15618009
2003 Metastasis-suppressor KAI1/CD82 induces homotypic aggregation of human prostate cancer cells through Src-dependent pathway. Experimental & molecular medicine 45 12642901
2023 The retrotransposon R2 maintains Drosophila ribosomal DNA repeats. Proceedings of the National Academy of Sciences of the United States of America 44 37252996
2011 Metastasis suppressor KAI1/CD82 attenuates the matrix adhesion of human prostate cancer cells by suppressing fibronectin expression and β1 integrin activation. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 44 21691075
2021 KAI1(CD82) is a key molecule to control angiogenesis and switch angiogenic milieu to quiescent state. Journal of hematology & oncology 43 34530889
2008 Transmembrane interactions are needed for KAI1/CD82-mediated suppression of cancer invasion and metastasis. The American journal of pathology 42 19116362
2014 ΔNp63α activates CD82 metastasis suppressor to inhibit cancer cell invasion. Cell death & disease 40 24901051
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
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
2023 Structural RNA components supervise the sequential DNA cleavage in R2 retrotransposon. Cell 36 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
2015 Hepatitis B virus induces RNR-R2 expression via DNA damage response activation. Journal of hepatology 34 26026873
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
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
2004 CD82, and CD63 in thyroid cancer. International journal of molecular medicine 31 15375577
2015 miR-203 Inhibits Frizzled-2 Expression via CD82/KAI1 Expression in Human Lung Carcinoma Cells. PloS one 30 26132195
2013 CD82/KAI expression prevents IL-8-mediated endothelial gap formation in late-stage melanomas. Oncogene 30 23873025
2009 Expression and clinical significance of p53, JunB and KAI1/CD82 in human hepatocellular carcinoma. Hepatobiliary & pancreatic diseases international : HBPD INT 30 19666408
2008 KAI1/CD82 is a novel target of estrogen receptor-mediated gene repression and downregulated in primary human breast cancer. International journal of cancer 30 18712725
2014 Identification of RNA binding motifs in the R2 retrotransposon-encoded reverse transcriptase. Nucleic acids research 29 24957604
2007 Effect of KAI1/CD82 on the beta1 integrin maturation in highly migratory carcinoma cells. Biochemical and biophysical research communications 29 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 28 31212375
1997 MRP-1/CD9 and KAI1/CD82 expression in normal and various cancer tissues. International journal of oncology 28 21528303
2021 PEDF is an endogenous inhibitor of VEGF-R2 angiogenesis signaling in endothelial cells. Experimental eye research 27 34742690
2012 KAI1 suppresses HIF-1α and VEGF expression by blocking CDCP1-enhanced Src activation in prostate cancer. BMC cancer 27 22390300
2003 GABAB receptor subunits, R1 and R2, in brainstem catecholamine and serotonin neurons. Brain research 27 12706246
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 The metastasis suppressor CD82/KAI1 regulates cell migration and invasion via inhibiting TGF-β 1/Smad signaling in renal cell carcinoma. Oncotarget 26 28881668
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 Role of Metastasis Suppressor KAI1/CD82 in Different Cancers. Journal of oncology 25 34306081
2016 Immunohistochemical expression pattern of metastasis suppressors KAI1 and KISS1 in endometriosis and normal endometrium. European journal of obstetrics, gynecology, and reproductive biology 25 26918694
2019 CD82 controls CpG-dependent TLR9 signaling. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 24 31408613
2012 Expression and clinical significance of CD82/KAI1 and E-cadherin in non-small cell lung cancer. Archives of Iranian medicine 24 23102249
2011 N-Glycosylation pattern of recombinant human CD82 (KAI1), a tumor-associated membrane protein. Journal of proteomics 24 22123080
2014 Clinicopathological significance of cancer stem cells marked by CD133 and KAI1/CD82 expression in laryngeal squamous cell carcinoma. World journal of surgical oncology 23 24758564
2009 KAI1/CD82 decreases Rac1 expression and cell proliferation through PI3K/Akt/mTOR pathway in H1299 lung carcinoma cells. Cell biochemistry and function 23 19107873
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
2018 CD82 hypomethylation is essential for tuberculosis pathogenesis via regulation of RUNX1-Rab5/22. Experimental & molecular medicine 21 29760437
2014 Alternative splicing of KAI1 abrogates its tumor-suppressive effects on integrin αvβ3-mediated ovarian cancer biology. Cellular signalling 21 25435431
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
2023 Inhibition of CD82 improves colitis by increasing NLRP3 deubiquitination by BRCC3. Cellular & molecular immunology 20 36600050
2018 Tetraspanin CD82 affects migration, attachment and invasion of rheumatoid arthritis synovial fibroblasts. Annals of the rheumatic diseases 20 29980577
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
2018 The tetraspanin CD82 regulates bone marrow homing and engraftment of hematopoietic stem and progenitor cells. Molecular biology of the cell 19 30133344
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
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
2020 CD82 Suppresses ADAM17-Dependent E-Cadherin Cleavage and Cell Migration in Prostate Cancer. Disease markers 17 33204367
2017 TIMP-1 and CD82, a promising combined evaluation marker for PDAC. Oncotarget 17 28030805
2002 Expression of metastasis suppressor gene (KAI1/CD82) in oral squamous cell carcinoma and its clinico-pathological significance. Oral oncology 17 12167433
2022 Tau R2 and R3 are essential regions for tau aggregation, seeding and propagation. Biochimie 16 35623497
2016 Tetraspanin CD82 Regulates the Spatiotemporal Dynamics of PKCα in Acute Myeloid Leukemia. Scientific reports 16 27417454
2009 Expression of KAI1/CD82 in distant metastases from estrogen receptor-negative breast cancer. Cancer science 16 19549254
2023 Structure of a ribonucleotide reductase R2 protein radical. Science (New York, N.Y.) 15 37797025
2022 Tetraspanin CD82 restrains phagocyte migration but supports macrophage activation. iScience 15 35754722
2020 CD82-TRPM7-Numb signaling mediates age-related cognitive impairment. GeroScience 15 32088828
2017 Overexpression of KAI1/CD82 suppresses in vitro cell growth, migration, invasion and xenograft growth in oral cancer. Molecular medicine reports 15 28260006
2017 TAp73 inhibits cell invasion and migration by directly activating KAI1 expression in colorectal carcinoma. Cancer letters 15 29222041

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