Affinage

ICAM1

Intercellular adhesion molecule 1 · UniProt P05362

Length
532 aa
Mass
57.8 kDa
Annotated
2026-06-10
100 papers in source corpus 26 papers cited in narrative 26 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ICAM-1 (CD54) is a cell-surface adhesion and signaling receptor that orchestrates leukocyte trafficking, immune cell function, and pathogen entry (PMID:1980124, PMID:28373581). It serves as a counter-receptor for the leukocyte integrins LFA-1 and Mac-1 (CD11b/CD18), mediating firm adhesion between stimulated neutrophils and endothelial cells (PMID:1980124), and also engages CD43 as an additional counter-ligand (PMID:1683685). Beyond passive adhesion, ICAM-1 is a bidirectional signaling molecule: endothelial engagement activates ERK, p38, and JNK MAPKs, with JNK driving F-actin rearrangement and paxillin phosphorylation that promotes VE-cadherin internalization to permit lymphocyte transendothelial migration, while the same MAPKs drive inflammatory gene expression (PMID:28373581). Clustering of endothelial ICAM-1 triggers a distinct clathrin- and caveolin-independent endocytic route dependent on dynamin-2, actin, Src, and ROCK (PMID:12640043), and its membrane mobility and clustering are governed by alpha-actinin linkage and tyrosine phosphorylation (PMID:16930678). ICAM-1 also transduces survival signals: fibrinogen binding induces cytoskeleton-dependent ERK-1/2 hyperphosphorylation and anti-apoptotic A1 upregulation in endothelium (PMID:10903502). As an entry receptor for ~90% of human rhinovirus serotypes, ICAM-1 binding induces capsid conformational changes—VP4 C-terminus translocation, disruption of RNA-VP2 contacts, and genome redistribution—that prime the virus for uncoating and genome release (PMID:10812972, PMID:33947819). ICAM-1 transcription is controlled by multiple inputs including p53 via intronic response elements (PMID:12660163), the mineralocorticoid receptor (PMID:28089144), FOXO1 in dendritic cells (PMID:25786691), and NF-κB (PMID:26666474), and is repressed by NANOG via p300 displacement (PMID:31619256) and post-transcriptionally by miR-222 (PMID:26081516) and stabilized translationally by Musashi-1 (PMID:30959276). Functionally, ICAM-1 is required cell-intrinsically for ILC2 development through ERK/GATA3 signaling (PMID:30049704), supports macrophage phagocytosis downstream of TLR4/ROS (PMID:33474594), and contributes to cancer cell invasion and stem cell self-renewal via p38-Notch1 (PMID:15774488, PMID:28042317).

Mechanistic history

Synthesis pass · year-by-year structured walk · 24 steps
  1. 1990 High

    Established that ICAM-1 is not solely an LFA-1 ligand but also a counter-receptor for the integrin Mac-1, broadening its role in neutrophil-endothelial adhesion.

    Evidence Reciprocal binding with purified Mac-1 and ICAM-1, transfected COS/L cells, antibody blocking, and conjugate assays

    PMID:1980124

    Open questions at the time
    • Affinity and stoichiometry of the Mac-1 interaction not quantified
    • Downstream signaling from Mac-1 engagement not addressed
  2. 1991 Medium

    Identified CD43 as an additional ICAM-1 counter-ligand, expanding the repertoire of ICAM-1 adhesion partners beyond integrins.

    Evidence Purified immobilized CD43 binding assay with Daudi cells

    PMID:1683685

    Open questions at the time
    • Physiological context of CD43-ICAM-1 binding unclear
    • No reciprocal validation or structural mapping
  3. 1992 Medium

    Distinguished signaling routes inducing ICAM-1, showing PKC-dependent induction is mechanistically separate from cytokine/LPS-driven induction.

    Evidence Kinase inhibitors and PMA/ionomycin treatment with ELISA/IP in HUVEC

    PMID:1347198

    Open questions at the time
    • Specific cytokine-induced kinases not identified
    • Transcription factors mediating each route undefined
  4. 1994 Medium

    Showed ICAM-1 on target cells costimulates NK cytotoxicity through remote signaling rather than direct target adhesion, implicating it in NK effector function.

    Evidence Three-cell cytotoxicity system with ICAM-1- vs LFA-3-transfected costimulators

    PMID:7518755

    Open questions at the time
    • Mechanism of 'remote' signaling not defined
    • Receptor on NK cells transmitting the signal unclear
  5. 1995 Medium

    Demonstrated ICAM-1 is coupled to intracellular signaling and can negatively modulate BCR-induced calcium flux in B cells.

    Evidence Intracellular Ca2+ measurement with mIgM/CD54 co-ligation in Burkitt lymphoma cells

    PMID:7843226

    Open questions at the time
    • Signaling intermediates linking ICAM-1 to Ca2+ suppression unknown
    • Physiological relevance to B cell biology not established
  6. 2000 High

    Revealed ICAM-1 as a survival receptor, with fibrinogen ligation activating ERK to suppress endothelial apoptosis.

    Evidence Apoptosis assays, ERK phosphorylation, recognition peptides, dominant-negative ERK, MEK inhibitor in endothelial cells

    PMID:10903502

    Open questions at the time
    • Cytoplasmic adaptor coupling ICAM-1 to ERK not identified
    • In vivo relevance of fibrinogen-ICAM-1 survival signaling untested
  7. 2000 Medium

    Showed ICAM-1 expression in vascular smooth muscle is phenotype-dependent and uses an adenylyl cyclase route distinct from NF-κB/PKC.

    Evidence Immunofluorescence, flow cytometry, pharmacological inhibitors in primary rat aortic SMC

    PMID:10704620

    Open questions at the time
    • Transcription factors downstream of adenylyl cyclase not identified
    • Single-species (rat) primary cells
  8. 2003 High

    Defined p53 as a direct transcriptional activator of ICAM-1 via intronic response elements, linking DNA damage to adhesion molecule expression independent of NF-κB.

    Evidence p53 inhibitor, p53-null cell lines, intronic element mapping, reporter assays

    PMID:12660163

    Open questions at the time
    • Physiological setting of p53-driven ICAM-1 induction unclear
    • Cofactors at intronic elements not characterized
  9. 2003 High

    Discovered that ICAM-1 clustering activates a novel dynamin/actin/Src/ROCK-dependent endocytic pathway, defining how engaged ICAM-1 is internalized.

    Evidence Anti-ICAM-1 conjugate uptake, dominant-negative dynamin-2, pathway inhibitors, colocalization, actin staining in HUVEC

    PMID:12640043

    Open questions at the time
    • Cargo and fate of internalized ICAM-1 not fully traced
    • Link between this pathway and leukocyte transmigration not established
  10. 2003 Medium

    Identified bacterial proteolysis of ICAM-1 by P. gingivalis gingipains as an immune evasion mechanism that disrupts neutrophil adhesion.

    Evidence Flow cytometry/Western of cleaved ICAM-1, fixed-cell proteolysis, PMN adhesion assay

    PMID:14514759

    Open questions at the time
    • Cleavage sites not mapped
    • In vivo contribution to periodontal immune evasion untested
  11. 2005 Medium

    Established a causal role for ICAM-1 in cancer cell invasion independent of proliferation or migration.

    Evidence siRNA knockdown and blocking antibody in Matrigel invasion assay in breast cancer cells

    PMID:15774488

    Open questions at the time
    • Molecular mediators of invasion downstream of ICAM-1 not identified
    • Limited to single cancer cell line
  12. 2006 Medium

    Linked ICAM-1 membrane mobility and clustering to alpha-actinin cytoskeletal coupling, which is lost in senescent endothelium.

    Evidence Single particle tracking, alpha-actinin co-IP, tyrosine phosphorylation assay in early vs late passage endothelial cells

    PMID:16930678

    Open questions at the time
    • Kinase phosphorylating alpha-actinin not identified
    • Functional consequence for leukocyte capture in senescence not measured
  13. 2015 High

    Identified FOXO1 as a direct ICAM-1 promoter activator and showed ICAM-1 is the key effector of FOXO1 in dendritic cell phagocytosis and chemotaxis.

    Evidence ChIP, reporter assays, lineage-specific FOXO1 knockout, ICAM-1 rescue, DC functional assays

    PMID:25786691

    Open questions at the time
    • How ICAM-1 promotes DC chemotaxis mechanistically unclear
    • Other FOXO1 targets contributing to phenotype not excluded
  14. 2015 Medium

    Showed IL-33 induces mast cell ICAM-1 via NF-κB to promote LFA-1-dependent adhesion, integrating ICAM-1 into allergic effector responses.

    Evidence IL-33 stimulation, NF-κB inhibitor, ICAM-1 siRNA, adhesion assay, in vivo IL-33 injection

    PMID:26666474

    Open questions at the time
    • Specific NF-κB subunits at the ICAM-1 promoter not defined
    • Downstream signaling from mast cell ICAM-1 not addressed
  15. 2015 Medium

    Established post-transcriptional control of ICAM-1 by microparticle-delivered miR-222, modulating endothelial monocyte adhesion in atherosclerosis.

    Evidence miRNA array, EMP-mediated miR-222 transfer, mRNA/protein readouts, adhesion assay, ApoE-/- mice

    PMID:26081516

    Open questions at the time
    • Direct ICAM-1 3'UTR target site not mapped
    • Other miR-222 targets contributing in vivo not excluded
  16. 2017 High

    Demonstrated that endothelial ICAM-1 engagement signals through ERK/p38/JNK MAPKs, with JNK driving paxillin-dependent VE-cadherin internalization to enable lymphocyte transendothelial migration and inflammatory gene expression.

    Evidence Antibody clustering/adhesion, MAPK inhibitors, co-IP of paxillin with VE-cadherin, internalization and TEM assays across two endothelial types

    PMID:28373581

    Open questions at the time
    • Direct kinase substrate linking ICAM-1 to JNK not defined
    • How JNK selectively phosphorylates paxillin not resolved
  17. 2017 Medium

    Implicated ICAM-1 in cancer stem cell self-renewal and tumorigenesis through the p38-Notch1 axis in prostate cancer.

    Evidence CD54 silencing, PDX and xenograft models, self-renewal assays, p38-Notch1 pathway dissection

    PMID:28042317

    Open questions at the time
    • How ICAM-1 activates p38 in cancer stem cells unclear
    • Receptor partner triggering this axis not identified
  18. 2017 High

    Identified the mineralocorticoid receptor as a direct transcriptional driver of endothelial ICAM-1 and showed ICAM-1 is the effector of aldosterone's pro-atherogenic effects.

    Evidence Promoter deletion/reporter assays defining an MRE, ApoE-/-/ICAM-1-/- double-knockout aldosterone atherosclerosis model

    PMID:28089144

    Open questions at the time
    • MR cofactors at the ICAM-1 promoter not characterized
    • Cell types beyond endothelium not examined
  19. 2018 High

    Revealed a cell-intrinsic requirement for ICAM-1 in ILC2 development and IL-33-driven cytokine production via ERK-dependent maintenance of GATA3.

    Evidence ICAM-1-deficient mice, CLP transfer, in vitro culture, IL-33 challenge, ERK/GATA3 analysis

    PMID:30049704

    Open questions at the time
    • How ICAM-1 cell-intrinsically activates ERK in ILC2s unknown
    • Ligand engaging ICAM-1 in this context not identified
  20. 2019 Medium

    Showed Musashi-1 binds ICAM-1 mRNA and promotes its translation to drive glioblastoma motility and invasion, defining a translational layer of ICAM-1 control.

    Evidence RNA immunoprecipitation, MSI1 knockdown, ICAM-1 overexpression rescue, motility/invasion assays

    PMID:30959276

    Open questions at the time
    • MSI1 binding site on ICAM-1 mRNA not mapped
    • Whether translation enhancement requires other RBPs unknown
  21. 2019 Medium

    Established that NANOG directly represses ICAM-1 by displacing p300 at the locus, enabling prostate cancer NK cell immune evasion.

    Evidence ChIPseq of NANOG and p300, NANOG overexpression, NK cytotoxicity, SCID xenograft

    PMID:31619256

    Open questions at the time
    • Mechanism of p300 displacement by NANOG unclear
    • Other repressive cofactors not characterized
  22. 2021 High

    Provided high-resolution structural mechanism showing ICAM-1 binding to rhinovirus 14 induces capsid conformational changes that prime genome release.

    Evidence Cryo-EM of rhinovirus 14 alone and complexed with ICAM-1 at 2.4 Å

    PMID:33947819

    Open questions at the time
    • Sequence of events between binding and uncoating at acidic pH not temporally resolved
    • Membrane penetration step not visualized
  23. 2021 Medium

    Showed macrophage ICAM-1, induced via TLR4-mediated ROS, is required for LPS-enhanced phagocytosis, linking innate sensing to ICAM-1 effector function.

    Evidence ICAM-1 neutralizing antibody, siRNA, TLR4-KO mice, ROS measurement, phagocytosis assay

    PMID:33474594

    Open questions at the time
    • How ICAM-1 promotes phagocytic uptake mechanistically unclear
    • Phagocytic ligand engaging ICAM-1 not identified
  24. 2021 Medium

    Demonstrated that ICAM-1 in non-irradiated tumors enhances CD8+ T cell activation and infiltration to promote the abscopal effect of radiotherapy.

    Evidence ICAM-1 knockout, adenoviral ICAM-1, TLR7 agonist nanodrug, imaging, CD8+ T cell flow cytometry, tumor growth

    PMID:33785590

    Open questions at the time
    • Mechanism by which tumor ICAM-1 enhances CD8+ T cell activation unresolved
    • Translatability to clinical radiotherapy untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the ICAM-1 cytoplasmic tail mechanistically couples surface engagement to the diverse MAPK, survival, and lineage-specific transcriptional programs across cell types remains undefined.
  • No unifying model of cytoplasmic adaptor recruitment
  • Cell-type specificity of ICAM-1 outside-in signaling not explained
  • Structural basis of integrin (LFA-1/Mac-1) engagement not resolved in the corpus

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0001618 virus receptor activity 2 GO:0060089 molecular transducer activity 2 GO:0098631 cell adhesion mediator activity 2
Localization
GO:0005886 plasma membrane 3
Pathway
R-HSA-168256 Immune System 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-162582 Signal Transduction 2 R-HSA-1643685 Disease 2
Partners
ACTN1CD43FGAITGALITGAMITGB2MSI1VE-CADHERIN

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1990 ICAM-1 (CD54) functions as a counter-receptor for Mac-1 (CD11b/CD18) in addition to LFA-1. Purified Mac-1 and ICAM-1 bind each other in reciprocal cell binding assays using transfected cell lines and immunoaffinity-purified proteins; this interaction mediates adhesion between stimulated neutrophils and stimulated endothelial cells. Reciprocal cell binding assays with purified proteins, transfected COS and L cells expressing Mac-1 or ICAM-1, antibody blocking, two-color fluorescence conjugate assays The Journal of cell biology High 1980124
1991 CD43 (sialophorin/leukosialin) binds ICAM-1 (CD54). Daudi cells bind specifically to purified immobilized CD43, and ICAM-1 was identified as a ligand for CD43 on Daudi cells. Purified immobilized CD43 binding assay, identification of ICAM-1 as the Daudi cell surface ligand Nature Medium 1683685
2003 Clustering of endothelial ICAM-1 triggers a novel clathrin- and caveolin-independent endocytic pathway that requires dynamin-2, actin rearrangements, Src kinase, and Rho kinase (ROCK), and stimulates formation of actin stress fibers. Internalization requires multimeric (not monomeric) antibody conjugates. Uptake of anti-ICAM-1 conjugates by endothelial cells; dominant-negative dynamin-2 constructs; pharmacological inhibitors of clathrin, caveolae, macropinocytosis, Src, and ROCK; colocalization studies; actin staining in HUVEC Journal of cell science High 12640043
2003 p53 activates ICAM-1 transcription via two functional p53-responsive elements located in the introns of the ICAM-1 gene, in an NF-κB-independent manner. DNA damage-induced ICAM-1 expression is abolished by the p53 inhibitor pifithrin-alpha and abrogated in p53-deficient cell lines. p53 inhibitor (pifithrin-alpha), p53-deficient cell lines, mapping of p53-responsive elements in ICAM-1 introns, reporter assays, NF-κB inhibition experiments The EMBO journal High 12660163
2000 Fibrinogen (Fg) binding to ICAM-1 mediates endothelial cell survival through an anti-apoptotic mechanism. Fg:ICAM-1 ligation induces hyperphosphorylation of ERK-1/2 (8-10 fold) in a cytoskeleton-dependent manner, activating the MAP kinase pathway and upregulating survival factor A1; blocking with ICAM-1(8-22) peptide or dominant-negative ERK-1/2 causes apoptosis. Annexin V binding apoptosis assay, ERK-1/2 phosphorylation assays, recognition peptides (Fg-gamma-(117-133) and ICAM-1(8-22)), MEK-1 inhibitor (PD 98059), cytoskeleton disruption (cytochalasin B, nocodazole), dominant-negative ERK-1/2 transfection European journal of biochemistry High 10903502
2000 ICAM-1 expression by vascular smooth muscle cells (SMC) is phenotype-dependent: freshly isolated SMC with high myofilament content express little ICAM-1 (non-inducible by IL-1β), whereas phenotypically modulated SMC with low myofilament content constitutively express ICAM-1 and upregulate it further with IL-1β. Signaling involves adenylyl cyclase but not protein kinase C or NF-κB. Immunofluorescence staining, flow cytometry, pharmacological inhibitors of PKC (chelerythrine), PTK (genistein), NF-κB (PDTC), and adenylyl cyclase (forskolin) in primary rat aortic SMC Atherosclerosis Medium 10704620
1992 Protein kinase C activation (by PMA) induces ICAM-1 expression through a staurosporine-sensitive pathway, whereas IL-1β, TNF-α, and LPS induce ICAM-1 via distinct kinase pathway(s) insensitive to staurosporine. Ionomycin acts synergistically with PMA but not with cytokines or LPS in upregulating ICAM-1. Protein kinase inhibitors (H-7, HA1004, staurosporine), ionomycin treatment, ELISA and immunoprecipitation of biosynthetically labeled ICAM-1 in HUVEC The American journal of physiology Medium 1347198
2017 Endothelial ICAM-1 engagement activates ERK, p38, and JNK MAPKs; JNK (and to a lesser degree p38) is the principal MAPK mediating lymphocyte diapedesis across both cerebral and dermal microvascular endothelial cells, whereas ERK is additionally required for TEM across dermal MVECs. JNK drives ICAM-1-induced F-actin rearrangements and phosphorylation of paxillin, which associates with VE-cadherin and promotes its internalization, facilitating lymphocyte TEM. ERK, p38, and JNK also regulate ICAM-1-dependent inflammatory gene expression (TNF-α, CXCL8, CCL3, CCL4, VCAM-1, COX-2). ICAM-1 engagement by lymphocyte adhesion and antibody clustering; MAPK inhibitors; F-actin staining; paxillin phosphorylation/co-immunoprecipitation with VE-cadherin; VE-cadherin internalization assays; CD4+ lymphocyte TEM assays across cerebral and dermal MVECs Journal of immunology (Baltimore, Md. : 1950) High 28373581
1995 Co-ligation of ICAM-1 (CD54) with membrane IgM on B cells inhibits BCR-induced intracellular Ca2+ mobilization (both from intracellular stores and extracellular influx), demonstrating that ICAM-1 is coupled to intracellular signaling pathways and can negatively modulate B cell receptor signaling. Intracellular Ca2+ measurement in Burkitt lymphoma B cells (MTLM4); co-ligation of mIgM and CD54 with limiting anti-IgM concentrations; multiple anti-CD54 mAb tested; Ca2+ measurements in presence and absence of extracellular Ca2+ European journal of immunology Medium 7843226
1994 ICAM-1 (CD54) on target cells provides costimulation for NK cell-mediated cytotoxicity via LFA-1/MAC-1 interactions. In a three-cell experimental system, ICAM-1-transfected cells (but not LFA-3-transfected cells) significantly enhanced NK cell lysis of K562 targets and anti-CD16-coated targets, acting through remote signaling rather than direct adhesion to target. Three-cell experimental system with NK cells, 51Cr-labeled target cells, and ICAM-1-transfected or LFA-3-transfected murine cells as costimulators; cytotoxicity assays Cellular immunology Medium 7518755
2005 ICAM-1 downregulation suppresses human breast cancer cell invasion through Matrigel without affecting proliferation or migration. Anti-ICAM-1 antibody blocks invasion of MDA-MB-435 cells dose-dependently, establishing a causal role for ICAM-1 in cancer cell invasion. ICAM-1 siRNA knockdown, anti-ICAM-1 antibody blocking, Matrigel invasion assay, cell proliferation assay in human breast cancer cell lines Carcinogenesis Medium 15774488
2021 Cryo-EM structure of rhinovirus 14 complexed with ICAM-1 at 2.4 Å resolution shows that ICAM-1 binding induces conformational changes in the rhinovirus 14 capsid, including translocation of VP4 C-termini, blocking of RNA-VP2 interactions, exposure of positively charged residues, and redistribution of the viral genome — priming the virus for activation and genome release at acidic pH. Cryo-EM structure determination of rhinovirus 14 alone (2.6 Å) and in complex with ICAM-1 (2.4 Å); structural analysis of conformational changes Proceedings of the National Academy of Sciences of the United States of America High 33947819
2003 Gingipains (cysteine proteinases) from Porphyromonas gingivalis directly cleave ICAM-1 on human oral epithelial cell surfaces in a time- and dose-dependent manner, disrupting ICAM-1-dependent PMN adhesion to epithelial cells, representing a mechanism of immune evasion. Flow cytometry and Western blotting of ICAM-1 on KB and HSC-2 cells; treatment with purified gingipain forms; fixed-cell proteolysis assay; PMN adhesion assay Journal of dental research Medium 14514759
2017 Aldosterone promotes endothelial ICAM-1 transcription through the mineralocorticoid receptor (MR). Luciferase reporter assays with deletion constructs of the ICAM-1 promoter in HUVECs identified a region containing an MR-responsive element (MRE) required for MR-dependent ICAM-1 transcriptional regulation. In vivo, ApoE/ICAM-1 double-knockout mice are protected from aldosterone-induced atherosclerotic plaque growth, confirming ICAM-1 as the effector of aldosterone's pro-atherogenic effects. Luciferase reporter assays with ICAM-1 promoter deletion constructs in HUVECs; ApoE-/-/ICAM-1-/- double-knockout mice; aldosterone-treatment atherosclerosis model International journal of cardiology High 28089144
2018 ICAM-1 is required cell-intrinsically for the development and function of group 2 innate lymphoid cells (ILC2s). ICAM-1-deficient mice have fewer ILC2s in bone marrow and peripheral tissues; CLP transfer and in vitro culture assays confirm cell-intrinsic regulation. ICAM-1 deficiency impairs ILC2 cytokine production in response to IL-33 via ERK signaling-dependent downregulation of GATA3. ICAM-1-deficient mice; CLP transfer assays; in vitro culture; IL-33 challenge; cytokine measurement; ERK signaling analysis; GATA3 protein quantification The Journal of experimental medicine High 30049704
2015 FOXO1 directly binds the ICAM-1 promoter, stimulates ICAM-1 transcriptional activity, and regulates ICAM-1 expression in dendritic cells (DCs). Transfection of ICAM-1-expressing plasmid into FOXO1-deleted DCs rescues impaired bacterial phagocytosis and chemotaxis, placing ICAM-1 as a key downstream effector of FOXO1 in DC function. ChIP showing FOXO1 binding to ICAM-1 promoter; FOXO1 promoter-luciferase reporter assays; lineage-specific FOXO1 knockout (CD11c.Cre+FOXO1L/L mice); rescue with ICAM-1-expressing plasmid; phagocytosis, chemotaxis, and DC homing assays Journal of immunology (Baltimore, Md. : 1950) High 25786691
2019 Musashi-1 (MSI1) promotes ICAM-1 translation in glioblastoma cells. RNA immunoprecipitation assays demonstrate that MSI1 physically interacts with ICAM-1 mRNA, and MSI1 knockdown suppresses ICAM-1 expression, cell motility, and invasion; overexpression of ICAM-1 reverses these effects. RNA immunoprecipitation (RIP) assay; MSI1 knockdown; ICAM-1 overexpression rescue; cell motility and invasion assays Neoplasia (New York, N.Y.) Medium 30959276
2017 CD54 (ICAM-1) mediates cancer stem cell self-renewal and tumorigenesis in prostate cancer through the p38-Notch1 signaling axis. Silencing CD54 reduces tumorigenesis in vitro and in vivo; dissection of downstream signaling identified p38-Notch1 as the principal pathway. CD54 silencing (siRNA/shRNA); patient-derived xenograft model; in vitro self-renewal assays; in vivo xenograft; pathway inhibition/dissection for p38-Notch1 Theranostics Medium 28042317
2021 ICAM-1 expression in non-irradiated tumors enhances activation and tumor infiltration of CD8+ T cells, thereby promoting the abscopal effect of radiotherapy. Genetic or pharmacologic upregulation of ICAM-1 markedly increases abscopal responses in animal models. ICAM-1 knockout; intratumoral injection of recombinant adenovirus encoding ICAM-1; TLR7 agonist nanodrug; PET/optical imaging of ICAM-1 expression; flow cytometry of CD8+ T cells; tumor growth measurements Proceedings of the National Academy of Sciences of the United States of America Medium 33785590
2021 Macrophage ICAM-1 expression, induced by LPS via TLR4-mediated ROS production, is required for LPS-enhanced macrophage phagocytosis. ICAM-1 neutralizing antibody or ICAM-1 siRNA silencing reduces LPS-induced phagocytosis; TLR4 knockout inhibits cytoplasmic and mitochondrial ROS production, which in turn attenuates ICAM-1 expression. ICAM-1 neutralizing antibody; ICAM-1 siRNA; TLR4 knockout mice; flow cytometry; confocal microscopy; ROS measurement; phagocytosis assay Inflammation research Medium 33474594
2006 In senescent endothelial cells, ICAM-1 transitions from directed to random motion within the membrane. Single particle tracking shows 44% reduced ICAM-1 mobility in late-passage cells after PKC stimulation, partly explained by reduced alpha-actinin linking with ICAM-1 and markedly reduced tyrosine phosphorylation of alpha-actinin (required for ICAM-1 clustering) in senescent cells. Single particle tracking; PKC activator (PMA); immunoprecipitation of alpha-actinin with ICAM-1; tyrosine phosphorylation assay; early vs. late passage HPAEC comparison Mechanisms of ageing and development Medium 16930678
2019 NANOG directly binds to the region upstream of the ICAM-1 gene, and increased NANOG binding is associated with diminished p300 binding at this region, resulting in decreased ICAM-1 expression. This mechanism enables prostate cancer cells to evade NK cell attack during tumorigenesis. RNAseq; ChIPseq of NANOG and p300 at the ICAM-1 upstream region; NANOG overexpression; NK cell cytotoxicity assays; xenograft in SCID mice Journal of experimental & clinical cancer research Medium 31619256
2015 MicroRNA-222 (miR-222) transported into endothelial cells by endothelial microparticles (EMP) post-transcriptionally downregulates ICAM-1 expression (mRNA and protein), reducing monocyte adhesion in vitro and endothelial ICAM-1 expression in ApoE-/- mice in vivo. Taqman microRNA array; miR-222 transfer via EMP; ICAM-1 mRNA and protein measurement; monocyte adhesion assay; ApoE-/- mouse in vivo model; miR-222 mimic/inhibitor experiments Journal of cellular and molecular medicine Medium 26081516
1996 CD30L and CD40L (but not 4-1BBL) upregulate ICAM-1 (CD54) surface expression and shedding in Hodgkin and Reed-Sternberg (H-RS) cells via transcriptional gene activation, as demonstrated at both mRNA and protein levels. Enhanced surface ICAM-1 is accompanied by increased shedding of an 82 kDa soluble CD54 form. CD30L and CD40L stimulation of H-RS cell lines; ICAM-1 mRNA and protein measurement; soluble CD54 measurement in culture supernatants Leukemia Low 8656679
2000 90% of human rhinovirus (HRV) serotypes use ICAM-1 as a cell-entry receptor. ICAM-1 positions the virus near the membrane and triggers a conformational change in the viral capsid leading to genome delivery across the lipid bilayer. Structural models from crystal structures of HRV and ICAM-1 fragments combined with EM reconstructions of complexes define receptor recognition and uncoating mechanism. Combined crystal structures of HRVs and ICAM-1 fragments with electron microscopy reconstructions of rhinovirus-ICAM-1 complexes Pharmaceutica acta Helvetiae Medium 10812972
2015 IL-33 induces ICAM-1 expression in murine mast cells via the NF-κB pathway, and this ICAM-1 upregulation increases mast cell adhesion to LFA-1-coated plates. Pre-treatment with an NF-κB inhibitor dramatically reduces IL-33-induced ICAM-1 expression. IL-33 stimulation of bone marrow-derived mast cells (BMMCs); NF-κB inhibitor; ICAM-1 siRNA transfection; cell adhesion assay to LFA-1-coated plate; in vivo IL-33 intradermal injection in mice with ICAM-1 immunohistochemistry Allergology international Medium 26666474

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1990 ICAM-1 (CD54): a counter-receptor for Mac-1 (CD11b/CD18). The Journal of cell biology 898 1980124
2009 ICAM-1 signaling in endothelial cells. Pharmacological reports : PR 553 19307690
2023 ICAM-1 and VCAM-1: Gatekeepers in various inflammatory and cardiovascular disorders. Clinica chimica acta; international journal of clinical chemistry 297 37442359
1991 CD43, a molecule defective in Wiskott-Aldrich syndrome, binds ICAM-1. Nature 270 1683685
2003 A novel endocytic pathway induced by clustering endothelial ICAM-1 or PECAM-1. Journal of cell science 254 12640043
1995 Expression of interleukin 8 and CD54 by human gastric epithelium after Helicobacter pylori infection in vitro. Gastroenterology 249 7806065
2005 Role of ICAM1 in invasion of human breast cancer cells. Carcinogenesis 230 15774488
1995 Ligation of CD40 on fibroblasts induces CD54 (ICAM-1) and CD106 (VCAM-1) up-regulation and IL-6 production and proliferation. Journal of leukocyte biology 201 7543921
2005 ICAM-1 co-stimulates target cells to facilitate antigen presentation. Current opinion in immunology 149 15886114
1989 MALA-2, mouse homologue of human adhesion molecule ICAM-1 (CD54). European journal of immunology 144 2571505
2009 Hug tightly and say goodbye: role of endothelial ICAM-1 in leukocyte transmigration. Antioxidants & redox signaling 135 18808323
2014 ICAM-1: isoforms and phenotypes. Journal of immunology (Baltimore, Md. : 1950) 128 24795464
2008 Soluble ICAM-1 and VCAM-1 as markers of endothelial activation. Scandinavian journal of immunology 122 18363595
1994 Polymorphisms and linkage analysis for ICAM-1 and the selectin gene cluster. Genomics 122 7525451
1991 Interleukin 4 promotes expression of mast cell ICAM-1 antigen. Proceedings of the National Academy of Sciences of the United States of America 119 1673030
1990 Differential expression of CD54/intercellular adhesion molecule-1 in myeloid leukemias and in lymphoproliferative disorders. Blood 116 1974471
1993 Coregulation of the APO-1 antigen with intercellular adhesion molecule-1 (CD54) in tonsillar B cells and coordinate expression in follicular center B cells and in follicle center and mediastinal B-cell lymphomas. Blood 115 7682455
2017 Role of LFA-1 and ICAM-1 in Cancer. Cancers 113 29099772
2015 Endothelial microparticles reduce ICAM-1 expression in a microRNA-222-dependent mechanism. Journal of cellular and molecular medicine 112 26081516
1992 Expression and regulation of adhesion molecules ICAM-1 (CD54) and LFA-3 (CD58) in human intestinal epithelial cell lines. Scandinavian journal of immunology 110 1376489
1992 Modulation and function of intercellular adhesion molecule-1 (CD54) on human retinal pigment epithelial cells. Laboratory investigation; a journal of technical methods and pathology 107 1346541
1991 Expression of cytoadhesion molecules (CD56, CD54, CD18 and CD29) by myeloma plasma cells. British journal of haematology 99 1721526
1993 Monoclonal antibodies against ICAM-1 (CD54) and LFA-1 (CD11a/CD18) inhibit experimental autoimmune uveitis. Clinical immunology and immunopathology 96 8100190
2017 Essential role of ICAM-1 in aldosterone-induced atherosclerosis. International journal of cardiology 93 28089144
2008 CD54 is a surrogate marker of antigen presenting cell activation. Cancer immunology, immunotherapy : CII 88 18297282
1997 Cell infiltration, ICAM-1 expression, and eosinophil chemotactic activity in asthmatic sputum. American journal of respiratory and critical care medicine 83 9032180
2017 Role of liver ICAM-1 in metastasis. Oncology letters 80 28943897
2003 p53 activates ICAM-1 (CD54) expression in an NF-kappaB-independent manner. The EMBO journal 80 12660163
2005 The role of ICAM-1 in Plasmodium falciparum cytoadherence. European journal of cell biology 77 15724813
1991 Expression of intercellular adhesion molecule-1 (CD54) on hematopoietic progenitors. Blood 77 1671649
1990 Induction of human thyroid cell ICAM-1 (CD54) antigen expression and ICAM-1-mediated lymphocyte binding. Endocrinology 73 1973649
2019 The ORMDL3 Asthma Gene Regulates ICAM1 and Has Multiple Effects on Cellular Inflammation. American journal of respiratory and critical care medicine 72 30339462
2004 ICAM-1: targeted docking for exogenous as well as endogenous ligands. Advanced drug delivery reviews 72 15063588
1999 Correlation of toxicity and pharmacokinetic properties of a phosphorothioate oligonucleotide designed to inhibit ICAM-1. Toxicologic pathology 72 10367680
2006 Hyaluronan-based polymer scaffold modulates the expression of inflammatory and degradative factors in mesenchymal stem cells: Involvement of Cd44 and Cd54. Journal of cellular physiology 69 16331675
2017 PAX7 Targets, CD54, Integrin α9β1, and SDC2, Allow Isolation of Human ESC/iPSC-Derived Myogenic Progenitors. Cell reports 68 28658631
1996 Heat shock protein 65 induces CD62e, CD106, and CD54 on cultured human endothelial cells and increases their adhesiveness for monocytes and granulocytes. Journal of immunology (Baltimore, Md. : 1950) 66 8683139
2000 Loss of B7.2 (CD86) and intracellular adhesion molecule 1 (CD54) expression is associated with decreased tumor-infiltrating T lymphocytes in diffuse B-cell large-cell lymphoma. Clinical cancer research : an official journal of the American Association for Cancer Research 65 11051236
2018 ICAM-1 controls development and function of ILC2. The Journal of experimental medicine 64 30049704
2003 Cytokine dependent inverse regulation of CD54 (ICAM1) and major histocompatibility complex class I antigens by nuclear factor kappaB in HEp2 tumor cell line: effect on the function of natural killer cells. Human immunology 62 12691701
2015 Rhamnogalacturonan I containing homogalacturonan inhibits colon cancer cell proliferation by decreasing ICAM1 expression. Carbohydrate polymers 61 26256381
1994 Regulation of ICAM-1 (CD54) expression in human breast cancer cell lines by interleukin 6 and fibroblast-derived factors. International journal of cancer 59 7516927
1994 CD54/ICAM-1 is a costimulator of NK cell-mediated cytotoxicity. Cellular immunology 59 7518755
1992 Discriminatory effects of protein kinase inhibitors and calcium ionophore on endothelial ICAM-1 induction. The American journal of physiology 58 1347198
2012 IL-6 promotes ICAM-1 expression and cell motility in human osteosarcoma. Cancer letters 56 22939995
2000 Fibrinogen interactions with ICAM-1 (CD54) regulate endothelial cell survival. European journal of biochemistry 55 10903502
1993 Immune modulation of adhesion molecules ICAM-1 (CD54) and LFA-3 (CD58) in human hepatocytic cell lines. Journal of hepatology 54 7686194
1991 Expression of the leucocyte integrin LFA-1 (CD11a/CD18) and its ligand ICAM-1 (CD54) in lymphoid malignancies is related to lineage derivation and stage of differentiation but not to tumor grade. Leukemia 54 1683677
2008 ICAM1 and VCAM1 polymorphisms, coronary artery calcium, and circulating levels of soluble ICAM-1: the multi-ethnic study of atherosclerosis (MESA). Atherosclerosis 53 18420209
2015 FOXO1 regulates dendritic cell activity through ICAM-1 and CCR7. Journal of immunology (Baltimore, Md. : 1950) 50 25786691
2021 Macrophage ICAM-1 functions as a regulator of phagocytosis in LPS induced endotoxemia. Inflammation research : official journal of the European Histamine Research Society ... [et al.] 48 33474594
2020 PD1 Blockade Enhances ICAM1-Directed CAR T Therapeutic Efficacy in Advanced Thyroid Cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 48 32887724
1993 De novo expression of intercellular adhesion molecule 1 (ICAM-1, CD54) in pancreas cancer. International journal of cancer 48 8093883
2017 Endothelial MAPKs Direct ICAM-1 Signaling to Divergent Inflammatory Functions. Journal of immunology (Baltimore, Md. : 1950) 47 28373581
2015 Regulation of ICAM-1 in cells of the monocyte/macrophage system in microgravity. BioMed research international 45 25654110
2003 Proteolysis of ICAM-1 on human oral epithelial cells by gingipains. Journal of dental research 45 14514759
1991 T-cell receptors and ICAM-1 expression in renal allografts during rejection. Transplant international : official journal of the European Society for Organ Transplantation 45 1958278
2017 CD54-NOTCH1 axis controls tumor initiation and cancer stem cell functions in human prostate cancer. Theranostics 44 28042317
2012 CCN3 increases cell motility and ICAM-1 expression in prostate cancer cells. Carcinogenesis 43 22345292
1999 Blocking ICAM-1 (CD54) and LFA-1 (CD11a) inhibits experimental allergic conjunctivitis. Clinical immunology (Orlando, Fla.) 43 10527686
2013 Intercellular adhesion molecule-1 (ICAM-1, CD54) is increased in adhesive capsulitis. The Journal of bone and joint surgery. American volume 42 23426775
1997 Regulation of RANTES and ICAM-1 expression in murine mesangial cells. Journal of the American Society of Nephrology : JASN 42 10495789
1993 Expression and shedding of ICAM-1 in bladder cancer and its immunotherapy. International journal of cancer 40 7902828
1992 Expression and functional role of CD54/Intercellular Adhesion Molecule-1 (ICAM-1) on human blood cells. Leukemia & lymphoma 40 1362919
2021 ICAM-1 orchestrates the abscopal effect of tumor radiotherapy. Proceedings of the National Academy of Sciences of the United States of America 38 33785590
2019 Musashi-1 Enhances Glioblastoma Migration by Promoting ICAM1 Translation. Neoplasia (New York, N.Y.) 38 30959276
1992 Characterization of the murine Icam-1 gene. Genomics 37 1362180
1992 Elevated expression of ICAM1 (CD54) and minimal expression of LFA3 (CD58) in Epstein-Barr-virus-positive nasopharyngeal carcinoma cells. International journal of cancer 37 1372880
2023 A YAP/TAZ-CD54 axis is required for CXCR2-CD44- tumor-specific neutrophils to suppress gastric cancer. Protein & cell 36 36921037
2022 Hindering the Synchronization Between miR-486-5p and H19 lncRNA by Hesperetin Halts Breast Cancer Aggressiveness Through Tuning ICAM-1. Anti-cancer agents in medicinal chemistry 35 33882812
2019 Human Neutrophils Will Crawl Upstream on ICAM-1 If Mac-1 Is Blocked. Biophysical journal 35 31585707
2006 Clonal senescence alters endothelial ICAM-1 function. Mechanisms of ageing and development 34 16930678
2012 CCN6 enhances ICAM-1 expression and cell motility in human chondrosarcoma cells. Journal of cellular physiology 33 21391218
1995 Differential expression and release of CD54 induced by cytokines. Hepatology (Baltimore, Md.) 33 7657294
2003 Intravenous immunoglobulin modulates lymphocyte CD54 and monocyte FcgammaRII expression in patients with chronic inflammatory neuropathies. Journal of neuroimmunology 32 12576228
1996 Expression of ICAM-1 and VCAM-1 in human malignant mesothelioma. The Journal of pathology 31 8774481
2020 A Rationally Designed ICAM1 Antibody Drug Conjugate for Pancreatic Cancer. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 30 33344137
2008 Variation in the ICAM1 gene is not associated with severe malaria phenotypes. Genes and immunity 30 18528404
2002 Strong expression of CD40, CD54 and HLA-DR antigen and lack of evidence for direct cellular cytotoxicity are unique immunohistopathological features in alopecia areata. Archives of dermatological research 30 12624779
2011 Highly osteogenic PDL stem cell clones specifically express elevated levels of ICAM1, ITGB1 and TERT. Cytotechnology 29 21866310
2019 ICAM-1 in HIV infection and underlying mechanisms. Cytokine 28 31491723
2019 NANOG helps cancer cells escape NK cell attack by downregulating ICAM1 during tumorigenesis. Journal of experimental & clinical cancer research : CR 28 31619256
2000 ICAM-1 receptors and cold viruses. Pharmaceutica acta Helvetiae 28 10812972
2024 Engineered Magneto-Piezoelectric Nanoparticles-Enhanced Scaffolds Disrupt Biofilms and Activate Oxidative Phosphorylation in Icam1+ Macrophages for Infectious Bone Defect Regeneration. ACS nano 27 39690461
2022 Fibrinogen promotes gallbladder cancer cell metastasis and extravasation by inducing ICAM1 expression. Medical oncology (Northwood, London, England) 27 36352295
1999 Altered expression of CD4, CD54, CD62L, and CCR5 in primary lymphocytes productively infected with the human immunodeficiency virus. AIDS research and human retroviruses 27 10029248
1995 Increased expression of adhesion molecules (CD54, CD29 and CD44) on fibroblasts infected with cytomegalovirus. Microbiology and immunology 26 7540252
2021 ICAM-1 induced rearrangements of capsid and genome prime rhinovirus 14 for activation and uncoating. Proceedings of the National Academy of Sciences of the United States of America 25 33947819
1996 Selective induction of CD11a,b,c/CD18 and CD54 expression at the cell surface of human leukocytes by muramyl peptides. Cellular immunology 25 8620558
1994 Expression of adhesion molecules CD11/CD18 (Leu-CAMs, beta 2-integrins), CD54 (ICAM-1) and CD58 (LFA-3) in B-chronic lymphocytic leukemia. Leukemia & lymphoma 25 7519509
1993 Expression of the Hermes-1 (CD44) and ICAM-1 (CD54) molecule on the surface of thyroid cells from patients with Graves' disease. Thyroid : official journal of the American Thyroid Association 25 7509669
2015 IL-33 promotes ICAM-1 expression via NF-kB in murine mast cells. Allergology international : official journal of the Japanese Society of Allergology 24 26666474
2013 Early cochlear response and ICAM-1 expression to cochlear implantation. Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology 24 23928509
2001 Production of polyclonal and monoclonal antibodies against CD54 molecules by intrasplenic immunization of plasmid DNA encoding CD54 protein. Immunology letters 24 11222909
2000 ICAM-1 expression by vascular smooth muscle cells is phenotype-dependent. Atherosclerosis 24 10704620
1995 The kinetics of surface expression of CD11/CD18 integrins and CD54 on monocytes and macrophages. Clinical and experimental immunology 23 7743678
1995 Co-ligation of ICAM-1 (CD54) and membrane IgM negatively affects B cell receptor signaling. European journal of immunology 23 7843226
1993 Increased ICAM-1 expression in aortic disease. Journal of vascular surgery 23 7693986
2019 Unprecedently high targeting specificity toward lung ICAM-1 using 3DNA nanocarriers. Journal of controlled release : official journal of the Controlled Release Society 21 31100312
1996 The CD30 ligand and CD40 ligand regulate CD54 surface expression and release of its soluble form by cultured Hodgkin and Reed-Sternberg cells. Leukemia 21 8656679

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