| 2003 |
PVR (CD155) was identified as a cell surface ligand for the activating NK cell receptor DNAM-1 (CD226). Protein purification, tryptic digestion, and mass spectrometry identified PVR as a ~70 kDa DNAM-1 ligand; PVR-Fc soluble hybrid molecules directly stained DNAM-1-transfected COS-7 cells, and PVR expression on target cell transfectants enhanced DNAM-1-dependent NK-mediated lysis. |
Protein purification, mass spectrometry, soluble Fc-fusion binding assay, cell transfection, NK cytotoxicity assay with blocking antibodies |
The Journal of experimental medicine |
High |
12913096 15607800
|
| 2004 |
DNAM-1 (CD226) binds both CD155 (PVR) and CD112 (nectin-2) with comparable affinities. Ectopic expression of CD155 or CD112 on mouse BW5147 T cells rendered them susceptible to IL-2-activated T and NK cell-mediated cytotoxicity in a CD226-dependent manner; ligation of CD226 and LFA-1 cooperated in triggering cytotoxicity and cytokine secretion. |
Soluble receptor binding affinity measurements, cell transfection, cytotoxicity assay with anti-CD226 blocking antibody |
International immunology |
High |
15039383
|
| 2004 |
PVR is expressed at cell-cell junctions of primary vascular endothelial cells and is the major DNAM-1 ligand at these junctions. The DNAM-1–PVR interaction is required for the diapedesis step of monocyte transendothelial migration: anti-PVR and anti-DNAM-1 antibodies arrested monocytes at the apical surface over intercellular junctions and blocked transmigration in vitro. |
Soluble DNAM-1-Fc binding assay on endothelial cells, blocking monoclonal antibodies, in vitro transendothelial migration assay |
The Journal of experimental medicine |
High |
15136589
|
| 2004 |
CD155 mediates tumor cell invasion and migration. FALI-mediated inactivation of CD155 or RNAi knockdown significantly decreased transwell migration of HT1080 fibrosarcoma and U87MG GBM cells. CD155 was recruited to the leading edge of migrating cells where it co-localized with actin and αv-integrin; knockdown altered cell morphology on Matrigel. |
FALI (Fluorophore Assisted Light Inactivation), RNAi knockdown, transwell invasion/migration assay, immunofluorescence co-localization |
BMC cancer |
High |
15471548
|
| 2003 |
Tage4/Necl-5 (mouse ortholog of CD155) heterophilically trans-interacts with nectin-3 but not homophilically with itself. This trans-interaction enhanced motility of V12Ras-NIH3T3 cells. Tage4 does not bind afadin, distinguishing it from canonical nectins. |
Cell-based ligand binding assay, cell motility assay, afadin binding assay |
The Journal of biological chemistry |
High |
12740392
|
| 2004 |
Necl-5/CD155 enhances serum- and PDGF-induced cell proliferation via the Ras-Raf-MEK-ERK signaling pathway, upregulating cyclins D2 and E, downregulating p27Kip1, and shortening the G0/G1 phase. Necl-5 acts downstream of PDGF receptor and upstream of Ras. Dominant-negative Necl-5 or blocking antibody suppressed these effects. |
Dominant-negative mutant expression, blocking antibody, cell cycle analysis, western blotting for signaling intermediates and cell cycle regulators |
The Journal of biological chemistry |
High |
15213219
|
| 2004 |
Necl-5/CD155 enhances serum- and PDGF-induced directional cell migration in a nectin-3-independent but integrin αVβ3-dependent manner. The extracellular region is required for directional migration; the cytoplasmic region is required for both directional and random motility. Necl-5 co-localizes with integrin αVβ3 at leading edges. Cdc42 and Rac are activated downstream of Necl-5 and are required for Necl-5-enhanced motility. |
Domain deletion mutant expression in L fibroblasts and NIH3T3 cells, integrin inhibitor/activator treatments, dominant-negative Necl-5, immunofluorescence co-localization, Rho GTPase activation assay |
The Journal of biological chemistry |
High |
14871893
|
| 2005 |
Cell-cell contact-induced interaction of Necl-5 with nectin-3 triggers clathrin-dependent endocytosis and down-regulation of Necl-5 from the cell surface, which subsequently reduces cell movement and proliferation, constituting a mechanism underlying contact inhibition. |
Immunofluorescence, clathrin inhibition, co-culture cell contact experiments, cell motility and proliferation assays |
The Journal of cell biology |
High |
16216929
|
| 2005 |
CD155/PVR expression in rat glioma cells enhances their dispersal in vitro and on primary brain tissue, reduces substrate adhesion, focal adhesion density, and actin stress fibers in a substrate-dependent manner. CD155/PVR increases Src/FAK signaling and enhances paxillin and p130Cas activation on vitronectin substrate. Depletion of endogenous CD155/PVR inhibits glioma cell migration and downregulates the same signaling pathway. |
Stable transfection/overexpression, RNAi knockdown, adhesion assays, immunofluorescence (focal adhesion counting), western blotting (Src, FAK, paxillin, p130Cas phosphorylation) |
Cancer research |
High |
16322240
|
| 2003 |
Nectin-3 binds CD155 and its mouse ortholog Tage4 in trans (heterophilic interaction). Coculture of nectin-3- and CD155-expressing cells led to CD155-dependent recruitment of nectin-3 to cell-cell contacts. CD155 co-distributes with αv integrin microdomains on the cell surface. CD155 dimerization facilitates the interaction. CD155 ectodomain binds vitronectin. |
Cell-based ligand binding assay, co-culture heterotypic contact experiments, immunofluorescence co-localization, coimmunoprecipitation (implied by dimerization analysis) |
The Journal of biological chemistry |
Medium |
12759359
|
| 2002 |
CD155 gene expression is transcriptionally activated by Sonic Hedgehog (Shh) signaling. Shh upregulated CD155 mRNA in human Ntera2 cells. Reporter gene driven by the CD155 core promoter was activated by Shh in co-transfection assays. An intact GLI binding site in the CD155 promoter is required for Shh activation. Overexpression of Gli1 or Gli3 potently activated CD155 promoter reporter expression. |
qRT-PCR, reporter gene (luciferase) assay, promoter mutagenesis (GLI binding site), Gli overexpression |
The Journal of biological chemistry |
High |
11983699
|
| 2005 |
Transcription of mouse Necl-5/CD155 is induced by FGF or oncogenic Ras through the Raf-MEK-ERK-AP-1 pathway. The Necl-5 promoter contains an AP-1 binding site required for V12Ki-Ras-induced activation. Inhibitors of the Raf-MEK-ERK pathway abrogated induction. |
Luciferase reporter gene assay, promoter mutagenesis (AP-1 site), pharmacological pathway inhibitors, oncogene (V12Ki-Ras) overexpression |
Oncogene |
High |
15688018
|
| 2003 |
Soluble CD155 (sCD155) isoforms exist in conditioned culture medium, human serum, and cerebrospinal fluid. sCD155 release does not require protease activity (indicating it is generated by alternative splicing rather than shedding). Serum-purified sCD155 reduces poliovirus entry mediated by membrane-bound CD155. |
ELISA, conditioned medium analysis with/without protease inhibitors, RT-PCR for splice variants, functional poliovirus entry inhibition assay |
Biochemical and biophysical research communications |
Medium |
12943679
|
| 2007 |
Necl-5/CD155 directly interacts in cis with integrin αVβ3, enhancing integrin αVβ3 clustering and focal complex formation at leading edges of moving cells. The extracellular region of Necl-5 (but not the cytoplasmic region) is necessary for the cis interaction with integrin αVβ3; both regions are necessary for the functional effect. Necl-5 enhances PDGF-induced Rac activation, facilitating integrin αVβ3 clustering in a feedback amplification manner. |
Co-immunoprecipitation of endogenous proteins, domain deletion mutants, integrin-vitronectin interaction assay, Rac activation assay (pull-down), immunofluorescence |
The Journal of biological chemistry |
High |
17446174
|
| 2008 |
Necl-5/CD155 interacts with PDGF receptor β at the leading edges of moving NIH3T3 cells and regulates the interaction between PDGF receptor and integrin αVβ3, effectively inducing directional cell movement. PDGF receptor co-localizes with Necl-5 and integrin αVβ3 at peripheral ruffles over lamellipodia. Clustering of these three molecules requires integrin αVβ3 activation by vitronectin and PDGF-induced Rac activation. |
Co-immunoprecipitation, immunofluorescence co-localization, Rac activation assay, dominant-negative constructs |
Genes to cells |
Medium |
18298801
|
| 2007 |
Necl-5/CD155 interacts with Sprouty2 (a negative regulator of growth factor signaling) and reduces the inhibitory effect of Sprouty2 on PDGF-induced Ras signaling. Upon Necl-5 down-regulation by nectin-3 trans-interaction at cell-cell contacts, Sprouty2 becomes tyrosine-phosphorylated by c-Src (activated by PDGF receptor), inhibiting PDGF-induced Ras signaling. This mechanism contributes to contact inhibition of proliferation. |
Co-immunoprecipitation, western blotting (phosphorylation), dominant-negative and constitutively active constructs, pharmacological inhibitors |
Genes to cells |
Medium |
17352739
|
| 2005 |
The trans-interaction of Necl-5 with nectin-3 bidirectionally activates Cdc42 and Rac GTPases via a common signaling pathway involving c-Src, Rap1 (through C3G), FRG (Cdc42-GEF), and Vav2 (Rac-GEF). This is the same cascade activated by nectin-nectin trans-interaction, and it contributes to adherens junction formation. |
GTPase activation assays (pull-down), co-immunoprecipitation, pharmacological and dominant-negative pathway perturbations |
Cancer science |
Medium |
16128743
|
| 2004 |
Necl-5 heterophilic trans-interaction with nectin-3 drives recruitment of afadin, E-cadherin, and catenins to the nectin-3 (but not Necl-5) side of cell-cell contact sites. Blocking the Necl-5/nectin-3 interaction with a specific monoclonal antibody inhibited formation of E-cadherin-based adherens junctions. |
Stable cell transfection (L cells expressing Necl-5, nectin-3, E-cadherin), immunofluorescence, function-blocking monoclonal antibody |
Genes to cells |
Medium |
15330856
|
| 2007 |
Necl-5/CD155 on cancer cells interacts in trans with CD226 on platelets, and this interaction promotes cancer cell adhesion to platelets in pulmonary vessels, enhancing lung metastasis. Overexpression of Necl-5 enhanced metastasis; anti-Necl-5 antibody blocking the Necl-5/CD226 interaction reduced metastasis. Platelet depletion abrogated the Necl-5-enhanced metastasis. |
Stable overexpression, in vivo tail-vein injection metastasis model, function-blocking monoclonal antibody, platelet depletion with anti-platelet serum |
Oncogene |
High |
17637752
|
| 2012 |
Necl-5/CD155 interacts with VEGFR2 (co-immunoprecipitation) and is required for VEGF-induced interaction of integrin αVβ3 with VEGFR2. Knockdown of Necl-5 in HUVECs inhibited VEGF-induced capillary network formation, migration, and proliferation, and suppressed VEGFR2-mediated activation of Rap1, Akt, and eNOS. Necl-5 knockout mice showed impaired post-ischemia blood flow recovery and VEGF-induced neovascularization. |
Co-immunoprecipitation, siRNA knockdown, in vitro angiogenesis assays (Matrigel, migration, proliferation, apoptosis), western blotting (Rap1, Akt, eNOS), Necl-5 knockout mouse model (hindlimb ischemia, Matrigel plug) |
Circulation research |
High |
22282193
|
| 2013 |
Endothelial PVR (CD155) interacts with monocyte DNAM-1 and regulates a step in transendothelial migration between PECAM and CD99. Activation of endothelial PVR (by antibody ligation or DNAM-1) recruits the tyrosine phosphatase Shp-2 in a Src kinase-dependent manner. PVR resides in the lateral border recycling compartment of endothelial cells, similar to PECAM and CD99. |
Sequential antibody blocking of TEM steps, Shp-2 recruitment assay, Src kinase inhibition, immunofluorescence localization to lateral border recycling compartment |
The American journal of pathology |
Medium |
23333754
|
| 2013 |
TLR signaling upregulates CD155 expression on antigen-presenting cells via MYD88, TRIF, and NF-κB (for most TLRs), and additionally requires IRF3 (but not IRF7) for TLR3-induced CD155 upregulation. CD155-deficient mice immunized with OVA/CpG showed increased OVA-specific IgG2a/c titers and lower IL-4 production and fewer GATA-3+IL-4+ CD4+ T cells, demonstrating that CD155 regulates Th2 differentiation. |
Genetic knockout mice (MYD88, TRIF, NF-κB, IRF3, IRF7, CD155), flow cytometry, ELISA |
PloS one |
Medium |
23349877
|
| 2015 |
CD155 knockdown in pancreatic cancer cells inhibited proliferation and induced cell-cycle arrest at G2/M phase, indicating a cell-intrinsic role for CD155 in tumor cell proliferation independent of immune mechanisms. |
siRNA/shRNA knockdown, cell proliferation assay, flow cytometry (cell cycle analysis) |
Anticancer research |
Medium |
25862891
|
| 2015 |
Nitric oxide (NO) donors upregulate PVR/CD155 surface and mRNA expression in multiple myeloma cells via activation of the DNA damage response (DDR) pathway involving ATM/ATR/Chk1/2 kinases, but independent of soluble guanylyl cyclase/cGMP. Specific inhibitors of ATM/ATR/Chk1/2 significantly abrogated the NO-induced CD155 upregulation. |
Flow cytometry, RT-PCR, pharmacological pathway inhibitors (ATM/ATR/Chk1/2 inhibitors, soluble guanylyl cyclase inhibitor), western blotting (DDR activation markers) |
BMC cancer |
Medium |
25609078
|
| 2016 |
Human CMV immediate early proteins IE1 and IE2 directly upregulate PVR/CD155 expression during HCMV infection via a mechanism independent of IE DNA binding activity (both IE1 and IE2 are required). IE2 directly activates the MICA promoter via a characterized IE2-responsive element. DNA damage response kinases (ATM, ATR, DNA-PK) are not involved in HCMV-induced CD155 upregulation. |
Overexpression of IE1/IE2, phosphonoformic acid inhibition of viral DNA replication, siRNA knockdown of ATM/ATR/DNA-PK, promoter analysis (IE2-responsive element characterization), flow cytometry and qRT-PCR |
Journal of immunology |
Medium |
27733551
|
| 2014 |
Activated unfolded protein response (UPR) decreases CD155 expression in hepatocellular carcinoma cells by two mechanisms: (1) ATF6 and IRE1α pathways suppress CD155 transcription/expression; (2) the IRE1α pathway upregulates the ERAD E3 ligase HRD1, which facilitates CD155 protein degradation. This UPR-induced CD155 downregulation reduces HCC sensitivity to NK cell cytotoxicity. |
Pharmacological UPR induction, pathway-specific siRNA knockdown (ATF6, IRE1α, HRD1), western blotting, flow cytometry, NK cell cytotoxicity assay |
European journal of immunology |
High |
25209846
|
| 2018 |
Crystal structure of CD96 first Ig domain (D1) bound to the CD155 (Necl-5) ectodomain was determined. CD96 recognizes CD155 D1 via a conserved 'lock-and-key' interaction shared across TIGIT:Necl complexes, but CD96 additionally uses a novel structural motif ('ancillary key') that confers specific CD155 recognition and distinguishes it from binding to nectin-2. Mutagenesis confirmed the ancillary key residue is critical for CD155 binding. |
X-ray crystallography, mutagenesis, direct binding assay |
Structure |
High |
30528596
|
| 2018 |
Crystal structure of the CD226 (DNAM-1) ectodomain bound to CD155 D1 revealed a unique side-by-side arrangement of two tandem IgV domains of CD226 (distinct from conventional head-to-tail). CD226 D1 mediates the conserved binding interface with CD155 D1, while CD226 D2 provides structural support and makes direct contacts with CD155. Deletion of D2 substantially reduced CD226 binding to CD155. |
X-ray crystallography (hybrid complex of mouse CD226 ectodomain + human CD155 D1), domain deletion binding assay |
Proceedings of the National Academy of Sciences of the United States of America |
High |
30591568
|
| 2020 |
Tumor-derived CD155 initiates phosphorylation of CD226 at tyrosine 319 (Y319) by Src kinases upon CD155-CD226 engagement. This phosphorylation enables ubiquitination of CD226 by the E3 ligase CBL-B, leading to internalization and proteasomal degradation of CD226. Mutation of Y319 prevents this degradation, resulting in increased CD226 surface expression and enhanced anti-tumor immunity. This represents a mechanism by which CD155 on tumor cells drives resistance to immunotherapy. |
CD226 Y319 point mutagenesis, phosphorylation assay, ubiquitination assay, co-immunoprecipitation (CBL-B interaction), flow cytometry (CD226 surface expression), in vivo tumor models, analysis of patient TILs |
Immunity |
High |
33053330
|
| 2020 |
Membrane-bound CD155 on tumor cells triggers CD226 internalization and degradation in NK cells, resulting in decreased NK cell-mediated tumor reactivity. IL-15 increases TIGIT and CD226 gene expression in tumor-infiltrating NK cells; combined IL-15 treatment with TIGIT blockade increases NK cell-mediated melanoma cytotoxicity in vitro and decreases tumor metastasis in two mouse melanoma models. CD226 blockade decreases the effects of IL-15 and TIGIT blockade. |
Flow cytometry (receptor internalization), in vitro cytotoxicity assay, two in vivo mouse melanoma models, genetic TIGIT deletion on transferred NK cells, IL-15 treatment |
Clinical cancer research |
High |
32591463
|
| 2020 |
PVRL1 (nectin-1) in hepatocellular carcinoma cells stabilizes cell-surface PVR/CD155 protein without affecting PVR mRNA levels. CD155 on HCC cells interacts with TIGIT on CD8+ effector memory T cells, suppressing anti-tumor immune response. Knockdown of Pvrl1 reduced cell-surface PVR levels and sensitized tumors to CD8+ T cell-mediated killing. Combined anti-PD1 and anti-TIGIT therapy significantly reduced tumor growth in mouse models. |
shRNA knockdown of Pvrl1, flow cytometry (surface PVR protein vs mRNA), co-culture cytotoxicity assays, CRISPR-Cas9 tumor models, in vivo antibody treatment (anti-TIGIT, anti-PD1, anti-CD8), mass cytometry (CyTOF) |
Gastroenterology |
High |
32275969
|
| 2018 |
CD155 loss in both host (Cd155-/- mice) and tumor cells reduces tumor growth and metastasis. Mechanistically, CD155 absence in the host leads to DNAM-1 (CD226) upregulation and enhanced effector function of CD8+ T and NK cells. CD155 deletion in tumor cells also reduces tumor growth (tumor-intrinsic role). Combined CD155 absence on host and tumor cells gives additive inhibition. PD-1 blockade is more effective in CD155-limiting settings. |
Cd155 germline knockout mice, CD155-deleted tumor cell lines, in vivo tumor growth and metastasis assays, flow cytometry (DNAM-1 expression, T/NK cell function), anti-PD-1 treatment |
The Journal of clinical investigation |
High |
29757192
|
| 2015 |
CD155/PVR mediates a costimulatory signal in CD4+ T cells promoting Th1 differentiation via NF-κB-induced autocrine IFN-γ that triggers positive feedback through STAT1 activation, independent of IL-12. Cd155-/- mice or anti-CD155 antibody-treated mice showed attenuated Th1-type contact hypersensitivity. |
CD155 signaling in primary T cells, cytokine measurement (IFN-γ), NF-κB inhibition, STAT1 activation analysis, IL-12 neutralization, Cd155 germline knockout mice, contact hypersensitivity model |
Journal of immunology |
Medium |
25972481
|
| 2022 |
KIR2DL5 on human NK cells binds PVR without competing with TIGIT, CD96, or DNAM-1. KIR2DL5-PVR engagement induces inhibitory immune synapse formation. Both intracellular ITIM and ITSM of KIR2DL5 undergo tyrosine phosphorylation, recruiting SHP-1 and/or SHP-2, which then downregulate Vav1/ERK1/2/p90RSK/NF-κB signaling to suppress NK cytotoxicity. |
Binding competition assays, inhibitory synapse imaging, phosphorylation assays, Co-IP (SHP-1/SHP-2 recruitment), ITIM/ITSM mutagenesis, western blotting (Vav1, ERK, NF-κB), NK cell cytotoxicity assays, humanized tumor mouse models |
The Journal of clinical investigation |
High |
36377656
|
| 2022 |
TIGIT, upon binding to CD155 and being phosphorylated, inhibits NF-κB and ERK activation in CD8+ T cells by recruiting SHIP-1, resulting in downregulation of cytokine production. Blocking TIGIT attenuates the inhibitory effect of SHIP-1 and restores NF-κB and ERK activation. |
Western blotting (NF-κB, ERK phosphorylation, SHIP-1 interaction), co-culture with CD155+ tumor cells, TIGIT blockade, in vivo tumor model |
Journal of translational medicine |
Medium |
35729552
|
| 2010 |
Knockdown of Necl-5/CD155 in A172 GBM cells decreases invasion in a 3D matrix, reduces MMP-2 expression and activity, and diminishes basal Akt activation and ILK-dependent Akt activation in response to vitronectin. Necl-5, Akt, and ILK co-localize at focal contacts at the leading edge, suggesting integration of Akt signaling at the leading edge to induce MMP-2 expression. |
RNAi knockdown, 3D invasion assay, MMP-2 zymography, western blotting (Akt, ILK phosphorylation), immunofluorescence co-localization |
Journal of neuro-oncology |
Medium |
20680398
|
| 2010 |
Necl-5/CD155 enhances PDGF-induced growth of microtubules toward the plasma membrane at the leading edge of moving NIH3T3 cells in an integrin αVβ3-dependent manner. Necl-5 promotes PDGF-induced attraction of plus-end-tracking proteins (EB1, CLIP170, dynein intermediate chain, p150Glued/dynactin) near the plasma membrane at the leading edge. |
Live-cell imaging of GFP-tagged microtubule plus-end proteins, siRNA knockdown of Necl-5, integrin αVβ3 inhibition |
Genes to cells |
Medium |
20964795
|
| 2017 |
CD155 knockdown in colon cancer cells inhibited migration and invasion with reduced FAK, Src, and MMP-2 expression; suppressed proliferation; and increased Bax/Bcl-2 ratio resulting in increased apoptosis. |
shRNA lentiviral knockdown, migration/invasion assay, western blotting (FAK, Src, MMP-2, Bax, Bcl-2, cell cycle regulators), flow cytometry (apoptosis) |
Journal of cellular and molecular medicine |
Medium |
28816021
|
| 2021 |
Aryl hydrocarbon receptor (AhR) transcriptionally regulates CD155 expression on tumor-associated macrophages in a co-regulated manner with PD-L1. AhR inhibition in vivo reduced CD155 expression and reversed tumor immunosuppression in a murine tumor model. |
AhR inhibitor treatment in vitro and in vivo, gene expression analysis, correlation with AhR activity markers in human glioblastoma data |
Journal of immunology |
Medium |
33504618
|
| 2023 |
T cell-derived IL-22 induces high CD155 expression on cancer cells via IL-22 receptor signaling on tumor cells. Excessive CD226 activation by IL-22-induced CD155 leads to decreased CD226 surface levels and functionally impaired NK cells, elevating metastatic burden. Constitutional and T cell-specific deletion of Il22, or deletion of the IL-22 receptor on cancer cells, each reduced metastases to a similar degree. |
Conditional knockout mice (constitutional Il22 KO, T cell-specific Il22 KO, cancer cell IL-22 receptor KO), in vivo lung and breast cancer metastasis models, flow cytometry (NK cell CD226 expression and function) |
Immunity |
High |
36630913
|
| 2024 |
Platelet contact with cancer cells transcriptionally upregulates CD155 via the FAK/JNK/c-Jun cascade. CD155 on circulating tumor cells inhibits NK cell cytotoxicity exclusively through TIGIT engagement, not through CD96 or DNAM-1. Antibody blockade of CD155-TIGIT interaction restored NK immunosurveillance and attenuated tumor metastasis. |
Single-cell RNA sequencing, multiplex immunofluorescence, in vitro/ex vivo co-culture cytotoxicity assays, in vivo metastasis models, competition assay (TIGIT vs CD96 vs DNAM-1 blocking), western blotting (FAK/JNK/c-Jun pathway) |
Hepatology |
High |
38779918
|
| 2023 |
Brain metastasis cancer-associated fibroblasts (bmCAFs) secrete fucosylated PVR/CD155 that enhances invasive capacity of breast cancer cells. Mechanistically, HIF1α transcriptionally upregulates fucosyltransferase 11, which fucosylates PVR, triggering its secretion. Secreted fucosylated PVR modulates cell-cell junction and actin cytoskeletal signaling in breast cancer cells. |
Patient-derived bmCAF conditioned medium experiments, HIF1α overexpression, fucosyltransferase 11 knockdown, global phosphoproteomics, functional invasion assays |
Cell reports |
Medium |
37995180
|
| 2024 |
METTL1 mediates m7G methylation of PKM mRNA, enhancing PKM2 expression, which increases glycolysis and promotes H3K9 lactylation (H3K9la). Nuclear PKM2 dimer activates CD155 (PVR) transcription via H3K9la, promoting immune evasion in colorectal cancer. This creates a positive feedback loop (H3K9la activates METTL1 transcription). Knockdown of METTL1 reduced CD155 expression and enhanced CD8+ T cell-mediated tumor killing in vivo. |
m7G methylation assay, RNA stability analysis, RIP assay, ChIP (Cut&Run), western blotting, ECAR/lactate assays, in vivo knockout mouse model with CD155 blockade |
Journal of translational medicine |
Medium |
39741310
|
| 2023 |
In giant cell arteritis (GCA), macrophages retain CD155 in the endoplasmic reticulum and fail to traffic it to the cell surface. This defective surface translocation of CD155 creates antigen-presenting cells that expand CD4+CD96+ T cells, which differentiate toward the Th9 lineage and release IL-9 to drive vasculitis. |
Immunofluorescence (ER retention of CD155), flow cytometry, humanized mouse model of GCA with recombinant IL-9 and anti-IL-9 antibody, T cell differentiation assays |
Cell reports. Medicine |
Medium |
37075705
|
| 2024 |
CD155/PVR and B7-H6 (but not nectin-2/CD112) are critical and non-redundant ligands for formation of robust immunological synapses between AML cells and Vδ1+ γδ T (DOT) cells. CRISPR-mediated ablation of PVR or B7-H6 disrupted DOT-cell targeting of AML cells; PVR expression in primary AML samples predicted their elimination by DOT cells. |
CRISPR-Cas9 ablation of PVR, B7-H6, and CD112 in AML cell lines, immunological synapse imaging, in vitro cytotoxicity assays, primary AML sample analysis |
Blood |
High |
38437507
|
| 2008 |
CD155 enhances proliferation of ras-mutated cells through the cytoplasmic region including the ITIM motif. CD155DeltaCP (lacking the cytoplasmic region including ITIM) has reduced ability to enhance serum responsiveness. siRNA knockdown of endogenous CD155 in DLD-1 cells (mutant K-ras) suppressed serum responsiveness. |
Cytoplasmic domain deletion mutant (CD155DeltaCP), siRNA knockdown, cell proliferation assay, cell cycle analysis |
International journal of cancer |
Medium |
17893876
|
| 2024 |
PITPNC1 regulates CD155 expression on the surface of tumor cells through FASN. Gene knockdown experiments showed that PITPNC1 upregulates FASN, which in turn increases CD155 surface expression. Co-immunoprecipitation and immunofluorescence confirmed co-localization of PITPNC1 and FASN. Silencing PITPNC1 suppressed FASN/CD155, enhanced CD8+ T cell immune function, and reduced radioresistance in colorectal cancer models. |
Co-immunoprecipitation, immunofluorescence co-localization, siRNA and lentiviral knockdown/overexpression, in vitro co-culture with CD8+ T cells, in vivo tumor-bearing model, western blotting |
Journal of translational medicine |
Medium |
38291470
|