Affinage

CDCP1

CUB domain-containing protein 1 · UniProt Q9H5V8

Length
836 aa
Mass
92.9 kDa
Annotated
2026-06-09
100 papers in source corpus 35 papers cited in narrative 35 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

CDCP1 is a type I transmembrane glycoprotein that functions as a proteolytically activated scaffolding receptor and signaling hub driving cancer cell survival, migration, invasion, and metastasis (PMID:12660814, PMID:20551327, PMID:21220330). The full-length 135 kDa protein is cleaved at Arg-368/Lys-369 by serine proteases—with urokinase (uPA) acting as the master regulator both by cleaving CDCP1 directly and by activating plasmin—to generate a membrane-retained 70 kDa fragment and a shed ectodomain that remain tightly associated after cleavage (PMID:20551327, PMID:22179830, PMID:33859413, PMID:35166238). Only the cleaved fragment homodimerizes through its extracellular CUB2 domain, and this homophilic complex is required to recruit and activate Src family kinases, which phosphorylate CDCP1 on the intracellular tyrosines Y734, Y743, and Y762 (PMID:26876198, PMID:31524271, PMID:23300860). Phosphorylated Y734 is the critical residue for Src activation and metastatic behavior, and CDCP1 acts as a transmembrane platform that assembles Src and PKCδ into membrane microdomains (PMID:18269919, PMID:21220330, PMID:21994943). Downstream, cleaved CDCP1 complexes with active β1 integrin to drive FAK and PI3K/Akt survival signaling and suppress PARP1-mediated apoptosis (PMID:22179830, PMID:23208492), promotes β1 integrin inside-out activation through a Src–PKCδ–CDK5 axis (PMID:29511352), facilitates MT1-MMP trafficking to invadopodia for ECM degradation (PMID:23439492), and engages receptor tyrosine kinase signaling by binding HER2 through its intracellular domain and potentiating MET/STAT3 and Rac1 responses to HGF (PMID:25892239, PMID:35085554, PMID:33574034). Beyond canonical signaling, the CUB domains bind TGF-β1 directly to enhance Smad2 signaling (PMID:31302030), and CDCP1 reprograms lipid metabolism by inhibiting acyl-CoA synthetase (ACSL) activity to elevate fatty acid oxidation (PMID:28739932). CDCP1 abundance is set by multiple converging mechanisms: constitutive palmitoylation-dependent internalization and proteasomal degradation reversed by EGFR activation (PMID:24681947), FBXL14-mediated ubiquitination (PMID:29973690), transcriptional induction by HIF-2α and Ras/ERK (PMID:23378636, PMID:24939643), and post-transcriptional control by METTL3/YTHDF1 m6A modification and miR-1 (PMID:30796352, PMID:28537886). Independently of its oncogenic role, CDCP1 (CD318) is a ligand for CD6 that mediates T cell adhesion and chemotaxis, and CD6-driven cytoskeletal remodeling, with CDCP1-knockout mice protected in autoimmune disease models (PMID:28760953, PMID:35951427).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2003 Medium

    Established CDCP1 as a cell-surface, heavily N-glycosylated transmembrane glycoprotein that is tyrosine phosphorylated by a Src family kinase, defining its basic biochemical identity.

    Evidence Immunopurification, anti-phosphotyrosine Western blot, Src inhibitor and deglycosylation studies in tumor cells

    PMID:12660814

    Open questions at the time
    • Did not identify the specific SFK or the phosphorylated residues
    • No functional consequence of phosphorylation established
  2. 2008 Medium

    Showed CDCP1 acts as a transmembrane scaffold clustering at cell-cell contacts and phosphorylated at Y734 by SFKs to organize Src and PKCδ in membrane microdomains, defining its scaffolding role.

    Evidence Triton-resistant membrane fractionation and phosphorylation assays in epithelial cells

    PMID:18269919

    Open questions at the time
    • Functional/phenotypic consequence of the scaffold not yet tested in vivo
    • Role of proteolysis not yet linked
  3. 2010 High

    Identified the proteolytic activation mechanism—serine protease cleavage at R368/K369 generating a membrane-retained 70 kDa fragment that recruits Src and PKCδ—establishing CDCP1 as a protease-activated receptor.

    Evidence N-terminal sequencing, site-directed mutagenesis, protease inhibitor panel and mass spectrometry

    PMID:20551327

    Open questions at the time
    • The dominant physiological protease was not pinned down
    • Downstream survival/migration outputs not yet mapped
  4. 2011 High

    Defined Y734 as the essential residue for CDCP1-driven SFK activation and metastasis, and showed CDCP1 and FAK-Y861 compete as SFK substrates without forming a trimeric complex, clarifying signaling logic.

    Evidence SILAC mass spectrometry, Y734F/Y743F/Y762F mutagenesis, 3D Matrigel and in vivo metastasis assays, SFK inhibitors and Co-IP

    PMID:21220330 PMID:21994943

    Open questions at the time
    • Did not resolve how substrate switching is controlled at endogenous expression levels
    • Relationship of Y734 signaling to proteolysis still implicit
  5. 2012 High

    Established the in vivo cleaved-CDCP1 survival and invasion program: plasmin cleavage recruits Src/PKCδ to activate Akt and suppress apoptosis, complexes with active β1 integrin to drive FAK/PI3K, and routes MT1-MMP to invadopodia.

    Evidence Cleavage-blocking antibodies, plasminogen-knockout mice, lung retention and spontaneous metastasis models, reciprocal Co-IP, siRNA, and invadopodia/Matrigel assays

    PMID:22179830 PMID:23208492 PMID:23300860 PMID:23439492

    Open questions at the time
    • Did not establish which protease dominates across tissues
    • Structural basis of the cleaved fragment's activity unresolved
  6. 2013 Medium

    Placed CDCP1 downstream of hypoxia (HIF-2α induction) and defined antibody-induced clustering as a trigger for Src-dependent phosphorylation, internalization, and proteasomal degradation, linking expression and turnover to function.

    Evidence HIF-1α/HIF-2α shRNA, hypoxic migration assays, xenografts, antibody-clustering and detergent-resistant membrane fractionation

    PMID:23378636 PMID:24055141

    Open questions at the time
    • Direct HIF-2α promoter occupancy not detailed
    • Mechanism coupling clustering to degradation incompletely defined
  7. 2014 High

    Resolved CDCP1 protein homeostasis (constitutive palmitoylation-dependent internalization/degradation reversed by EGFR) and its position downstream of oncogenic Ras/ERK linking Ras to Src signaling and MMP activation.

    Evidence Palmitoylation-site mutagenesis, EGF treatment, proteasome inhibitors, live-cell internalization assays, and Ras-mutant lung cancer knockdown with zymography

    PMID:24681947 PMID:24939643

    Open questions at the time
    • Identity of palmitoyltransferase not determined
    • How EGFR blocks palmitoylation mechanistically unresolved
  8. 2015 Medium

    Expanded the interactome by showing CDCP1 binds HER2 intracellularly to enhance HER2/c-Src signaling and trastuzumab resistance, and that SHP2 binds phospho-Y734/Y743 to modulate phosphorylation and internalization.

    Evidence Reciprocal Co-IP with domain mapping, point mutants (Y734A/Y743A), SHP2 shRNA, functional and in vivo tumor assays

    PMID:25876044 PMID:25892239

    Open questions at the time
    • SHP2 substrate specificity on CDCP1 not fully defined
    • Interplay between SHP2 dephosphorylation and SFK binding kinetics unclear
  9. 2016 High

    Demonstrated that only the cleaved form homodimerizes via its ectodomain to drive PKCδ/ERK/p38 phosphorylation and migration, establishing dimerization of the proteolytic fragment as the activation switch.

    Evidence Full-length vs cleaved constructs in HEK293T, Co-IP for dimerization, ectodomain blocking fragment, and migration rescue in TNBC

    PMID:26876198

    Open questions at the time
    • Stoichiometry and structural geometry of the dimer not defined here
    • Whether dimerization precedes or follows SFK recruitment unresolved
  10. 2017 High

    Broadened CDCP1 function into metabolism (ACSL inhibition driving fatty acid oxidation), immune ligand biology (CD6 ligand mediating T cell adhesion/chemotaxis and autoimmune disease), and added miRNA/ADAM9-EGFR regulation of its expression.

    Evidence ACSL activity assays, CARS lipid imaging, genetic rescue, CD318/CD6 knockout mice in EAU, adhesion/chemotaxis assays, and miR-1 3'-UTR reporter with ADAM9 epistasis

    PMID:28537886 PMID:28739932 PMID:28760953

    Open questions at the time
    • Structural basis of CDCP1-ACSL inhibition undefined
    • How CD6 engagement signals into CDCP1-expressing cells incompletely mapped
  11. 2018 High

    Defined a CDCP1-driven Src–PKCδ–CDK5 cascade controlling β1 integrin inside-out activation and adhesion, and added FBXL14/miR-17-20a as a ubiquitin-degradation control of CDCP1 levels.

    Evidence siRNA, CDK5R1-Y234 and CDK5-T77 phospho-site mutagenesis, PKCδ C2-domain binding, integrin activation/adhesion assays, FBXL14 Co-IP and ubiquitination assays

    PMID:29511352 PMID:29973690

    Open questions at the time
    • In vivo relevance of the CDK5 arm not fully tested
    • FBXL14 recognition determinants on CDCP1 not mapped
  12. 2019 High

    Established direct extracellular ligand binding (CUB domains bind TGF-β1/BMP4 with selective enhancement of TGF-β/Smad2 signaling), CUB2-mediated homophilic complex formation as the SFK-activating unit, Wnt/β-catenin promotion, and m6A translational control.

    Evidence BIAcore SPR, TGF-β reporter and phospho-Smad2 assays, CUB2 deletion/blocking experiments, cell fractionation for β-catenin, and METTL3/YTHDF1/ALKBH5 m6A profiling

    PMID:30796352 PMID:31302030 PMID:31471585 PMID:31524271

    Open questions at the time
    • How extracellular ligand binding integrates with proteolytic activation unresolved
    • Structural detail of CUB-ligand complexes lacking
  13. 2021 High

    Identified urokinase as the master protease driving CDCP1 cleavage and metastasis, and extended CDCP1 signaling to HGF/MET-STAT3 in renal regeneration and to dendritic cell IL-6/Syk-MAPK in Kawasaki disease.

    Evidence Substrate-biased activity-based probe with MS protease identification and in vivo metastasis models; lipid raft fractionation/STAT3 analysis in nephrectomy model; CDCP1 KO mice in CAWS-induced disease

    PMID:33574034 PMID:33859413 PMID:34099547

    Open questions at the time
    • Relative contributions of uPA vs plasmin in different tissues not quantified
    • DC and renal signaling mechanisms only partially dissected
  14. 2022 High

    Structurally characterized the cleaved fragments as remaining tightly associated, enabling cleavage-selective neoepitope antibodies for targeted therapy, and defined HGF-driven CDCP1-SRC-ARHGEF7-RAC1 migration signaling and CD6-mediated RPE barrier disruption.

    Evidence SPR/structural analysis and differential phage display antibodies in syngeneic pancreatic model; Rac1 activation and ARHGEF7 colocalization assays; CDCP1 knockdown in RPE with barrier/T-cell migration assays and EAU KO model

    PMID:35085554 PMID:35166238 PMID:35951427

    Open questions at the time
    • High-resolution structure of full cleaved complex not reported
    • Therapeutic neoepitope antibody efficacy beyond preclinical models untested
  15. 2025 Medium

    Defined N339/N386 glycosylation as functional determinants of CDCP1-driven SRC/JUN phosphorylation and migration, identified CDCP1 enrichment in metastatic-cell extracellular vesicles, and a CDCP1-dependent PDGFRβ endocytosis pathway in vascular smooth muscle.

    Evidence Site-specific glycosylation mutagenesis with glycoproteomics/phosphoproteomics and EV profiling in lung cancer; CDCP1 siRNA with PDGFRβ/NEDD4/clathrin/Rab5 Co-IP and carotid stenosis model

    PMID:40256729 PMID:40693605

    Open questions at the time
    • How specific glycans modulate signaling mechanistically unresolved
    • Vascular and EV roles validated in single labs only

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how the multiple inputs—proteolytic activation, extracellular ligand engagement, glycosylation, and degradation control—are integrated to dictate which downstream program (integrin, RTK, metabolic, or immune) CDCP1 selects in a given cell context.
  • No high-resolution structure of the full-length or cleaved CDCP1 signaling complex
  • Context determinants of pathway choice undefined
  • Physiological (non-cancer) function only partially characterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 5 GO:0060090 molecular adaptor activity 4 GO:0048018 receptor ligand activity 2 GO:0098772 molecular function regulator activity 2
Localization
GO:0005886 plasma membrane 5 GO:0031410 cytoplasmic vesicle 2 GO:0005739 mitochondrion 1
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-1643685 Disease 3 R-HSA-168256 Immune System 3 R-HSA-1474244 Extracellular matrix organization 2 R-HSA-392499 Metabolism of proteins 2 R-HSA-1430728 Metabolism 1
Partners
ACSL3CD6ERBB2FBXL14ITGB1PRKCDSHP2SRC

Evidence

Reading pass · 35 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 SIMA135/CDCP1 is a type I transmembrane glycoprotein located on the cell surface, with up to 40 kDa of its apparent molecular weight attributable to N-glycosylation. It is tyrosine phosphorylated in tumor cells, and selective inhibitor studies indicated that a Src kinase family member is responsible for this phosphorylation. Immunopurification, Western blot with anti-phosphotyrosine antibody, selective Src kinase inhibitor studies, deglycosylation analysis Oncogene Medium 12660814
2008 CDCP1 (Gp140) clusters in epithelial cell-cell contacts and is phosphorylated by Src Family Kinases at tyrosine 734 in response to outside-in signals. Active SFKs mediate phosphorylation of CDCP1, SFK, and PKCδ, with CDCP1 acting as a transmembrane scaffold for these kinases within membrane microdomains. Biochemical fractionation (Triton-resistant membrane domains), phosphorylation assays, cell biology experiments Biochimica et biophysica acta Medium 18269919
2010 Full-length 135 kDa CDCP1 is post-translationally processed by serine protease activity (including matriptase) at two sites, Arg-368 and Lys-369, generating a C-terminal membrane-retained 70 kDa fragment and a shed N-terminal 65 kDa ectodomain. Proteolysis induces tyrosine phosphorylation of the 70 kDa fragment and recruitment of Src and PKCδ to this fragment. Immunopurification, N-terminal sequencing, detailed mutagenesis, protease inhibitor panel, Western blot, mass spectrometry The Journal of biological chemistry High 20551327
2011 CDCP1 overexpression activates Src family kinases in melanoma cells, and the Y734F point mutation in CDCP1 abolishes Src activation, dispersive 3D growth in Matrigel, and in vivo metastasis-enhancing activity, establishing that Y734 is required for CDCP1's metastasis-promoting function through SFK activation. SILAC quantitative mass spectrometry, point mutagenesis (Y734F), 3D Matrigel culture, in vivo metastasis assay, pharmacological SFK inhibitors (PP2, Dasatinib) Proceedings of the National Academy of Sciences of the United States of America High 21220330
2011 CDCP1-Tyr-734 and FAK-Tyr-861 compete as Src family kinase (SFK) substrates. Stable CDCP1 expression causes SFK-mediated phosphorylation of CDCP1-Y734 with concomitant loss of phospho-FAK-Y861, and this substrate switching is dependent on expression level and Y734 but not Y743 or Y762. FAK does not form a trimeric complex with Src and CDCP1. Stable CDCP1 expression in HeLa cells, phosphorylation analysis (Western blot), mutagenesis (Y734F, Y743F, Y762F), siRNA knockdown, co-immunoprecipitation (negative result for trimeric complex) The Journal of biological chemistry High 21994943
2011 In vivo cleavage of CDCP1 by plasmin (identified as the crucial extracellular serine protease) triggers a survival signaling cascade: serine-protease-mediated 135→70 kDa CDCP1 cleavage recruits Src and PKCδ, Src-mediated phosphorylation of 70 kDa CDCP1 activates Akt, and suppresses PARP1-mediated apoptosis. Preventing CDCP1 cleavage with antibodies, protease inhibitors, or genetic mutation of the cleavage site abrogates this signaling and induces apoptosis. Anti-CDCP1 cleavage-blocking antibodies, serine protease inhibitors, genetic cleavage-site mutagenesis, plasminogen-knockout mice, lung retention model, Western blot for Src/PKCδ/Akt/PARP1 Oncogene High 22179830
2012 Proteolytic cleavage of CDCP1 by plasmin-like serine proteases generates a membrane-retained 70 kDa fragment that complexes preferentially with active (inside-out activated) β1 integrin, both in cell culture and in live animals. This complex activates intracellular FAK and PI3K/Akt signaling, promoting tumor cell intravasation and metastasis. Inhibition of FAK/PI3K or shRNA knockdown of β1 integrin reduces FAK/Akt phosphorylation downstream of cleaved CDCP1. Co-immunoprecipitation (cell culture and in vivo), cleavage-blocking antibody (10-D7), aprotinin (serine protease inhibition), FAK/PI3K inhibitors, β1 integrin shRNA, spontaneous metastasis assays in vivo Oncogene High 23208492
2012 CDCP1 is required for ECM degradation by invadopodia in breast cancer and melanoma cells. CDCP1 localizes to caveolin-1-containing vesicular structures and lipid rafts and co-immunoprecipitates with MT1-MMP, regulating its trafficking and accumulation at invadopodia; siRNA knockdown of CDCP1 markedly reduces MT1-MMP-dependent ECM degradation and Matrigel invasion. siRNA knockdown, co-immunoprecipitation (CDCP1 with MT1-MMP), immunofluorescence, lipid raft fractionation (Triton X-100 insoluble fraction), Matrigel invasion assay Molecular cancer research : MCR High 23439492
2013 HIF-2α (but not HIF-1α) directly induces CDCP1 expression and tyrosine phosphorylation under hypoxia. shRNA knockdown of CDCP1 impairs cancer cell migration under hypoxic conditions, establishing CDCP1 as a downstream HIF-2α target gene mediating hypoxia-driven metastasis. shRNA knockdown of HIF-2α and HIF-1α, shRNA knockdown of CDCP1, hypoxic cell migration assay, HIF-2α overexpression in xenografts Proceedings of the National Academy of Sciences of the United States of America Medium 23378636
2013 Antibody-induced CDCP1 clustering/dimerization transiently induces tyrosine phosphorylation of CDCP1 by Src, causes translocation of CDCP1 to a Triton X-100 insoluble fraction of the plasma membrane (requiring bivalency of the antibody), and subsequently triggers internalization and proteasome-dependent degradation of CDCP1 in a Src-dependent manner. Focus formation assay (NIH3T3 co-transformation with CDCP1 and Src), antibody (RG7287) treatment, Western blot for CDCP1 phosphorylation and levels, detergent-resistant membrane fractionation, xenograft models Molecular oncology Medium 24055141
2014 Oncogenic Ras/ERK signaling induces CDCP1 expression in lung cancer cells; CDCP1 knockdown or inhibition of CDCP1 phosphorylation by Src-directed therapy abrogates anoikis resistance, migration, invasion, and Ras-induced MMP2 activation/MMP9 secretion. CDCP1 is therefore required for the functional link between Ras and Src signaling. CDCP1 knockdown (siRNA/shRNA), Src-directed therapy, anoikis assay, migration assay, invasion assay, zymography (MMP2/MMP9), Ras mutant lung cancer cells Molecular cancer research : MCR Medium 24939643
2014 Under basal conditions, cell-surface CDCP1 constitutively internalizes and undergoes palmitoylation-dependent proteasomal degradation, palmitoylated at one or more cytoplasmic cysteines. EGF/EGFR activation inhibits this palmitoylation-dependent degradation, promotes recycling of CDCP1 to the cell surface, and increases cell migration. Disruption of CDCP1 palmitoylation also promotes its relocalization to the cell surface and cell migration. Palmitoylation site mutagenesis (cytoplasmic cysteines), EGF treatment, proteasome inhibitors, live-cell imaging/internalization assays, cell migration assay, in vivo palmitoylation detection in tumor samples Oncogene High 24681947
2015 CDCP1 binds to HER2 through its intracellular domain, increasing HER2 interaction with c-SRC, which enhances HER2 activation and downstream signaling and confers trastuzumab resistance in breast cancer cells. Co-immunoprecipitation (CDCP1 with HER2 and c-SRC), CDCP1 domain truncation analysis, cell migration, transformation, and in vivo tumor formation assays, trastuzumab resistance assays Cell reports High 25892239
2015 The tyrosine phosphatase SHP2 directly interacts with CDCP1 via its phosphorylated Y734 and Y743 residues (as shown by point mutants), potentially competing with SFK binding. shRNA-mediated downregulation of SHP2 results in stronger CDCP1 phosphorylation and impaired antibody-mediated CDCP1 internalization. Co-immunoprecipitation, affinity precipitation, CDCP1 point mutants (Y734A, Y743A), SHP2 shRNA knockdown PloS one Medium 25876044
2016 Only the cleaved form of CDCP1 (cCDCP1), not full-length CDCP1, is capable of homodimerization through its ectodomain, and only cCDCP1 induces phosphorylation of PKCδ, ERK1/2, and p38 MAPK and promotes cell migration. A blocking fragment of the cCDCP1 ectodomain (ECC) inhibits dimerization, PKCδ phosphorylation, and TNBC cell migration. Expression of full-length vs. cleaved CDCP1 constructs in HEK 293T, co-immunoprecipitation for dimerization, phosphorylation analysis (Western blot), migration rescue assay in CDCP1-shRNA TNBC lines, ECC blocking fragment Oncogene High 26876198
2017 CDCP1 drives a 'low-lipid' phenotype in triple-negative breast cancer by interacting with and inhibiting acyl CoA-synthetase ligase (ACSL) activity, reducing acyl-CoA production and increasing fatty acid oxidation (FAO) and oxidative phosphorylation in mitochondria. CDCP1 knockdown increases lipid droplet abundance and reduces migration, rescued by the ACSL inhibitor Triacsin C or ACSL3 co-knockdown. CDCP1 knockdown and rescue experiments, coherent anti-Stokes Raman scattering (CARS) and two-photon excited fluorescence microscopy (lipid droplet imaging), ACSL activity assay, Co-IP (CDCP1 with ACSL), in vivo animal models of TNBC with blocking fragment treatment Proceedings of the National Academy of Sciences of the United States of America High 28739932
2017 CD318/CDCP1 is a ligand for CD6. Soluble CD318 is chemoattractive to T cells, and CD318 participates in CD6-dependent adhesion of T cells to synovial fibroblasts. CD318 knockout mice are protected in experimental autoimmune encephalomyelitis, phenocopying CD6 KO mice. Identification via mAb 3A11, CD318 knockout mice in EAU model, T cell adhesion assay, T cell chemotaxis assay Proceedings of the National Academy of Sciences of the United States of America High 28760953
2018 Loss of CDCP1 reduces CDK5 kinase activity via a mechanism in which c-SRC phosphorylates CDK5R1/p35 on Y234, creating a binding site for the C2 domain of PKCδ, which in turn phosphorylates CDK5 on T77, causing dissociation of the CDK5R1/CDK5 complex and abolishing CDK5 activity. This loss of CDK5 activity reduces inside-out activation of β1 integrin, impairing cell adhesion and migration. CDCP1 siRNA silencing, phosphorylation mapping (CDK5R1-Y234, CDK5-T77), CDK5 phosphorylation site mutants (T77 and Y234), PKCδ C2 domain binding assay, β1 integrin inside-out activation assay, cell adhesion and migration assays Oncogene High 29511352
2018 FBXL14 E3 ubiquitin ligase directly interacts with CDCP1 and facilitates its ubiquitination and proteasomal degradation, thereby reducing CDCP1 protein stability. miR-17/20a suppress FBXL14, establishing an upstream regulatory mechanism for CDCP1 protein levels. Co-immunoprecipitation (CDCP1 with FBXL14), ubiquitination assay, proteasome inhibitor experiments, miR-17/20a overexpression Oncogene Medium 29973690
2019 CDCP1 promotes Wnt signaling in colorectal cancer by facilitating nuclear translocation of β-catenin and E-cadherin. Disruption of CDCP1 reduces nuclear chromatin-associated β-catenin and nuclear E-cadherin, increases sequestration of these proteins at cell membranes, and disrupts regulation of CRC-promoting genes. Cell fractionation, immunoprecipitation, immunofluorescence microscopy, immunohistochemistry, CDCP1 loss-of-function, in vitro and in vivo tumor models Oncogene Medium 31471585
2019 CDCP1 CUB domains bind directly to TGF-β1 and BMP4 (real-time protein interaction on BIAcore chip). CDCP1 enhances TGF-β1 signaling (reporter activity and phospho-Smad2 levels) but does not modulate BMP signaling. CDCP1 actions on TGF-β/Smad2 signaling require Smad2 and TGFRI but are independent of Src or PKCδ binding. BIAcore surface plasmon resonance (direct binding to TGF-β1 and BMP4), TGF-β reporter assay, phospho-Smad2 Western blot, siRNA knockdown of Smad2/TGFRI/Src/PKCδ Experimental cell research High 31302030
2019 CDCP1 forms a homophilic complex via its extracellular CUB2 domain; deletion of the extracellular region abolishes complex formation. The homophilic complex activates SFK on the plasma membrane and promotes cancer cell migration. A recombinant CUB2 domain protein (rMBP-CUB2) inhibits CDCP1 homophilic complex formation, SFK activation, and cancer cell migration. Deletion mutants, co-immunoprecipitation for dimerization, recombinant CUB2 domain blocking experiment, SFK phosphorylation assay, cancer cell migration assay Oncology reports Medium 31524271
2019 METTL3 and m6A reader YTHDF1 recognize m6A residues on CDCP1 3'-UTR mRNA and promote CDCP1 translation. ALKBH5 demethylase opposes this modification. Inhibition of the METTL3-m6A-CDCP1 axis reduces growth of transformed and bladder cancer cells. m6A profiling, METTL3/ALKBH5 knockdown, YTHDF1 binding assay, CDCP1 translation assay, in vitro and in vivo functional assays Oncogene Medium 30796352
2021 Urokinase (uPA) is identified as the master regulator of CDCP1 proteolysis, acting both by directly cleaving CDCP1 and by activating plasmin (which also cleaves CDCP1). uPA-mediated CDCP1 proteolysis promotes metastasis in disease-relevant preclinical in vivo models, and co-expression of uPA and CDCP1 is strongly predictive of poor disease outcome across multiple cancers. Substrate-biased activity-based probe (sbABP) incorporating CDCP1 cleavage motif, protease capture/isolation/identification (MS), in vivo metastasis models Nature chemical biology High 33859413
2021 CDCP1 on dendritic cells (DCs) is required for IL-6 production during Kawasaki disease model induction. CAWS stimulation upregulates CDCP1 on DCs, and CDCP1 KO DCs show significantly reduced IL-6 production associated with impaired Syk-MAPK signaling pathway activation. CDCP1 knockout mice, CAWS-induced Kawasaki disease model, IL-6 ELISA, immunostaining (DC subsets), Syk-MAPK pathway analysis Journal of immunology Medium 34099547
2022 Biochemical and biophysical characterization (SPR, structural analysis) revealed that the two cleaved fragments of CDCP1 remain tightly associated with minimal conformational change after proteolysis. Antibodies that selectively bind the proteolytic neoepitope of cleaved CDCP1 (with no detectable binding to uncleaved form) potently target cleaved CDCP1-expressing cancer cells as ADC, Ab-radionuclide conjugate, and bispecific T cell engager. Biochemical characterization, biophysical analysis (SPR), structural characterization, differential phage display to generate cleavage-selective antibodies, syngeneic pancreatic tumor model The Journal of clinical investigation High 35166238
2022 CDCP1 promotes HGF-induced cell migration and invasion by activating SRC kinase; in breast cancer cells, CDCP1 facilitates MET activation by HGF and promotes lamellipodia formation. CDCP1 expression activates small GTPase Rac1 via guanine nucleotide exchange factor ARHGEF7, which co-accumulates with CDCP1, establishing a CDCP1-SRC-ARHGEF7-RAC1 pathway. CDCP1 knockdown and ectopic expression, HGF stimulation assays, Rac1 activation assay, ARHGEF7 knockdown, immunofluorescence (CDCP1/ARHGEF7 colocalization), migration/invasion assays The Journal of biological chemistry Medium 35085554
2021 CDCP1 promotes HGF-induced compensatory renal growth by recruiting Src into lipid rafts to activate STAT3 associated with the HGF receptor Met; activated STAT3 induces expression of matrix metalloproteinases and mitogenic factors. CDCP1 ablation attenuates regenerative Met-STAT3 signaling after unilateral nephrectomy in mice. CDCP1 ablation in canine kidney cells, lipid raft fractionation (Src recruitment), STAT3 phosphorylation analysis (association with Met), MMP and mitogenic factor expression assay, unilateral nephrectomy mouse model Life science alliance Medium 33574034
2022 CDCP1 on RPE cells is upregulated by IFN-γ. CD6 stimulation of RPE cells induces increased barrier permeability, massive stress fiber formation, and focal adhesion disruption reducing tight junctions, facilitating T cell infiltration. This CD6-stimulated barrier disruption is abrogated by CDCP1 knockdown, establishing that CDCP1 mediates CD6-driven RPE cytoskeleton remodeling. CDCP1 knockdown in RPE cells, IFN-γ stimulation, CD6 stimulation, transwell T cell migration assay, RPE monolayer permeability assay, immunostaining for stress fibers and focal adhesions, EAU mouse model (CDCP1 KO) JCI insight Medium 35951427
2017 CDCP1 expression is inhibited by the microRNA miR-1, which directly targets the 3'-UTR of CDCP1 mRNA. ADAM9 promotes CDCP1 expression by activating EGFR signaling, which in turn suppresses miR-1 expression, establishing an ADAM9-EGFR-miR-1-CDCP1 regulatory axis. Luciferase reporter assay (miR-1 binding to CDCP1 3'-UTR), ADAM9 knockdown, EGFR signaling analysis, miR-1 inhibitor/mimic experiments, in vivo metastasis/survival assay Oncotarget Medium 28537886
2025 CDCP1 knockdown in vascular smooth muscle cells (VSMCs) inhibits PDGFRβ endocytosis by promoting PDGFRβ binding to NEDD4 and its ubiquitination, and attenuating PDGFRβ binding to clathrin and Rab5. This leads to reduced AKT signaling and decreased VSMC proliferation and migration. CDCP1 siRNA knockdown, RNA-seq, co-immunoprecipitation (PDGFRβ with NEDD4, clathrin, Rab5), immunofluorescence, CCK8 proliferation assay, wound healing assay, focal carotid stenosis in vivo model PeerJ Medium 40256729
2012 For CDCP1/Src-dependent cellular transformation, the intact amino- and carboxy-termini of CDCP1 are essential. Mutation of any of the three core intracellular tyrosine residues (Y734, Y743, or Y762) abolishes transformation capacity, and mutation of a palmitoylation motif (C689,690G) strongly reduces it. Src kinase binding to CDCP1 via its SH2 domain is not required for transformation, but Src myristoylation is necessary. Retrovirus-mediated co-overexpression of c-Src and CDCP1 in NIH3T3 cells, focus formation assay, CDCP1 truncation and point mutants (Y734F, Y743F, Y762F, C689/690G), Src SH2 domain mutant PloS one High 23300860
2014 CDCP1 and the tetraspanin CD9 are co-expressed and form a low-level but detectable complex in colon cancer cells, as shown by co-sedimentation in sucrose gradients and co-immunoprecipitation. CDCP1 modulates cell-substratum adhesion and serum-induced chemotaxis in colon cancer cell lines. Co-immunoprecipitation, density gradient centrifugation, siRNA knockdown, Matrigel adhesion assay, xCELLigence chemotaxis assay BMC cancer Low 25301083
2020 CDCP1 is transferred from metastatic prostate cancer cells to osteoclast precursors via extracellular vesicles (EVs) and promotes osteoclastogenesis in the presence of RANKL. Functional siRNA screening of EV cargo identified CDCP1 as the specific inducer of osteoclast formation. EV characterization, functional siRNA screening of EV cargo, osteoclastogenesis assay in presence of RANKL Journal of extracellular vesicles Medium 36880252
2025 Glycosylation of CDCP1 at N339 and N386 are identified as critical functional determinants. CDCP1 knockout reduces SRC and JUN phosphorylation (ErbB signaling pathway markers by 5.5-fold and 4.2-fold respectively) and reduces cancer cell migration. CDCP1 is selectively enriched in extracellular vesicles from highly metastatic lung cancer cells. CDCP1 knockout (KO) in lung cancer cells, intact glycopeptide enrichment with site-specific glycoform profiling, Ti4+-IMAC phosphoproteomics, site-specific glycosylation mutagenesis (N339, N386), migration assays, EV/cell co-culture Journal of extracellular vesicles Medium 40693605

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2017 CDCP1 drives triple-negative breast cancer metastasis through reduction of lipid-droplet abundance and stimulation of fatty acid oxidation. Proceedings of the National Academy of Sciences of the United States of America 161 28739932
2019 Dynamic m6A mRNA methylation reveals the role of METTL3-m6A-CDCP1 signaling axis in chemical carcinogenesis. Oncogene 156 30796352
2001 Identification of a novel gene, CDCP1, overexpressed in human colorectal cancer. Oncogene 117 11466621
2003 Subtractive immunization using highly metastatic human tumor cells identifies SIMA135/CDCP1, a 135 kDa cell surface phosphorylated glycoprotein antigen. Oncogene 116 12660814
2012 In vivo cleaved CDCP1 promotes early tumor dissemination via complexing with activated β1 integrin and induction of FAK/PI3K/Akt motility signaling. Oncogene 104 23208492
2011 CUB-domain-containing protein 1 (CDCP1) activates Src to promote melanoma metastasis. Proceedings of the National Academy of Sciences of the United States of America 83 21220330
2017 CD318 is a ligand for CD6. Proceedings of the National Academy of Sciences of the United States of America 81 28760953
2004 CDCP1 identifies a broad spectrum of normal and malignant stem/progenitor cell subsets of hematopoietic and nonhematopoietic origin. Stem cells (Dayton, Ohio) 66 15153610
2021 The CDCP1 Signaling Hub: A Target for Cancer Detection and Therapeutic Intervention. Cancer research 65 33509939
2010 Proteolysis-induced N-terminal ectodomain shedding of the integral membrane glycoprotein CUB domain-containing protein 1 (CDCP1) is accompanied by tyrosine phosphorylation of its C-terminal domain and recruitment of Src and PKCdelta. The Journal of biological chemistry 65 20551327
2014 Oncogenic Ras/ERK signaling activates CDCP1 to promote tumor invasion and metastasis. Molecular cancer research : MCR 62 24939643
2011 Blocking of CDCP1 cleavage in vivo prevents Akt-dependent survival and inhibits metastatic colonization through PARP1-mediated apoptosis of cancer cells. Oncogene 62 22179830
2021 Identification of CD318, TSPAN8 and CD66c as target candidates for CAR T cell based immunotherapy of pancreatic adenocarcinoma. Nature communications 61 33674603
2009 The cell surface glycoprotein CDCP1 in cancer--insights, opportunities, and challenges. IUBMB life 61 19514048
2013 Identification of CDCP1 as a hypoxia-inducible factor 2α (HIF-2α) target gene that is associated with survival in clear cell renal cell carcinoma patients. Proceedings of the National Academy of Sciences of the United States of America 56 23378636
2015 Interaction of CDCP1 with HER2 enhances HER2-driven tumorigenesis and promotes trastuzumab resistance in breast cancer. Cell reports 54 25892239
2003 CDCP1 is a novel marker for hematopoietic stem cells. Annals of the New York Academy of Sciences 52 12799299
2019 CDCP1 enhances Wnt signaling in colorectal cancer promoting nuclear localization of β-catenin and E-cadherin. Oncogene 42 31471585
2006 Epigenetic regulation of the expression of the novel stem cell marker CDCP1 in cancer cells. The Journal of pathology 40 16823897
2020 Programmable N6-methyladenosine modification of CDCP1 mRNA by RCas9-methyltransferase like 3 conjugates promotes bladder cancer development. Molecular cancer 39 33267838
2016 CDCP1 cleavage is necessary for homodimerization-induced migration of triple-negative breast cancer. Oncogene 39 26876198
2016 Cell line and patient-derived xenograft models reveal elevated CDCP1 as a target in high-grade serous ovarian cancer. British journal of cancer 39 26882065
2021 Prospective Identification of Elevated Circulating CDCP1 in Patients Years before Onset of Lung Cancer. Cancer research 38 33574093
2012 The cell surface glycoprotein CUB domain-containing protein 1 (CDCP1) contributes to epidermal growth factor receptor-mediated cell migration. The Journal of biological chemistry 38 22315226
2020 CDCP1 overexpression drives prostate cancer progression and can be targeted in vivo. The Journal of clinical investigation 37 32250342
2014 EGF inhibits constitutive internalization and palmitoylation-dependent degradation of membrane-spanning procancer CDCP1 promoting its availability on the cell surface. Oncogene 35 24681947
2023 Metastatic prostate cancer-derived extracellular vesicles facilitate osteoclastogenesis by transferring the CDCP1 protein. Journal of extracellular vesicles 34 36880252
2016 CDCP1 is a novel marker of the most aggressive human triple-negative breast cancers. Oncotarget 33 27626701
2007 Expression of the CUB domain containing protein 1 (CDCP1) gene in colorectal tumour cells. FEBS letters 33 17335815
2020 Theranostic Targeting of CUB Domain Containing Protein 1 (CDCP1) in Pancreatic Cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 32 32341034
2013 Antibody mediated CDCP1 degradation as mode of action for cancer targeted therapy. Molecular oncology 32 24055141
2011 Cellular settings mediating Src Substrate switching between focal adhesion kinase tyrosine 861 and CUB-domain-containing protein 1 (CDCP1) tyrosine 734. The Journal of biological chemistry 32 21994943
2008 The role of membrane microdomains in transmembrane signaling through the epithelial glycoprotein Gp140/CDCP1. Biochimica et biophysica acta 32 18269919
2017 ADAM9 enhances CDCP1 by inhibiting miR-1 through EGFR signaling activation in lung cancer metastasis. Oncotarget 31 28537886
2013 CDCP1 regulates the function of MT1-MMP and invadopodia-mediated invasion of cancer cells. Molecular cancer research : MCR 31 23439492
2022 Targeting a proteolytic neoepitope on CUB domain containing protein 1 (CDCP1) for RAS-driven cancers. The Journal of clinical investigation 30 35166238
2020 Effective targeting of intact and proteolysed CDCP1 for imaging and treatment of pancreatic ductal adenocarcinoma. Theranostics 28 32226543
2021 Methylation of microRNA-338-5p by EED promotes METTL3-mediated translation of oncogene CDCP1 in gastric cancer. Aging 27 33882457
2012 KAI1 suppresses HIF-1α and VEGF expression by blocking CDCP1-enhanced Src activation in prostate cancer. BMC cancer 27 22390300
2020 Anti-CDCP1 immuno-conjugates for detection and inhibition of ovarian cancer. Theranostics 26 32104500
2018 The PDGFRβ/ERK1/2 pathway regulates CDCP1 expression in triple-negative breast cancer. BMC cancer 25 29792166
2015 HIF-2α regulates CDCP1 to promote PKCδ-mediated migration in hepatocellular carcinoma. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 25 26307391
2022 Targeting CDCP1 gene transcription coactivated by BRD4 and CBP/p300 in castration-resistant prostate cancer. Oncogene 23 35513563
2023 Identification and multicentric validation of soluble CDCP1 as a robust serological biomarker for risk stratification of NASH in obese Chinese. Cell reports. Medicine 22 37918406
2022 AXL/CDCP1/SRC axis confers acquired resistance to osimertinib in lung cancer. Scientific reports 22 35643725
2023 Myocardial Recovery in Recent Onset Dilated Cardiomyopathy: Role of CDCP1 and Cardiac Fibrosis. Circulation research 21 37800334
2022 CUB Domain-Containing Protein 1 (CDCP1) Is a Target for Radioligand Therapy in Castration-Resistant Prostate Cancer, including PSMA Null Disease. Clinical cancer research : an official journal of the American Association for Cancer Research 20 35604681
2021 Substrate-biased activity-based probes identify proteases that cleave receptor CDCP1. Nature chemical biology 20 33859413
2021 CDCP1 on Dendritic Cells Contributes to the Development of a Model of Kawasaki Disease. Journal of immunology (Baltimore, Md. : 1950) 20 34099547
2020 Increased Plasma Levels of the Co-stimulatory Proteins CDCP1 and SLAMF1 in Patients With Autoimmune Endocrine Diseases. Frontiers in immunology 20 32983115
2018 Hepatic stem cells with self-renewal and liver repopulation potential are harbored in CDCP1-positive subpopulations of human fetal liver cells. Stem cell research & therapy 19 29402311
2018 Regulation of inside-out β1-integrin activation by CDCP1. Oncogene 18 29511352
2018 FBXL14 abolishes breast cancer progression by targeting CDCP1 for proteasomal degradation. Oncogene 18 29973690
2016 New crossroads for potential therapeutic intervention in cancer - intersections between CDCP1, EGFR family members and downstream signaling pathways. Oncoscience 18 26973855
2015 Dysregulated expression of cell surface glycoprotein CDCP1 in prostate cancer. Oncotarget 18 26497208
2013 Stratum basale keratinocyte expression of the cell-surface glycoprotein CDCP1 during epidermogenesis and its role in keratinocyte migration. The British journal of dermatology 18 23121233
2021 hsa_circ_0005358 suppresses cervical cancer metastasis by interacting with PTBP1 protein to destabilize CDCP1 mRNA. Molecular therapy. Nucleic acids 17 34976440
2017 Novel small molecule inhibiting CDCP1-PKCδ pathway reduces tumor metastasis and proliferation. Cancer science 17 28256037
2014 CDCP1 identifies a CD146 negative subset of marrow fibroblasts involved with cytokine production. PloS one 16 25275584
2010 CD318/CUB-domain-containing protein 1 expression on cord blood hematopoietic progenitors. Experimental and therapeutic medicine 14 22993567
2022 CDCP1 regulates retinal pigmented epithelial barrier integrity for the development of experimental autoimmune uveitis. JCI insight 13 35951427
2022 CUB Domain-Containing Protein 1 (CDCP1) is a rational target for the development of imaging tracers and antibody-drug conjugates for cancer detection and therapy. Theranostics 13 36276654
2019 CUB domain-containing protein 1 (CDCP1) binds transforming growth factor beta family members and increase TGF-β1 signaling pathway. Experimental cell research 13 31302030
2011 Infrared spectral signatures of CDCP1-induced effects in colon carcinoma cells. The Analyst 13 22034616
2022 CD318 is a target of chimeric antigen receptor T cells for the treatment of colorectal cancer. Clinical and experimental medicine 12 36495368
2017 Development of an enzyme-linked immunosorbent assay for detection of CDCP1 shed from the cell surface and present in colorectal cancer serum specimens. Journal of pharmaceutical and biomedical analysis 12 28279929
2014 CUB domain containing protein 1 (CDCP1) modulates adhesion and motility in colon cancer cells. BMC cancer 12 25301083
2012 Structural requirements for cub domain containing protein 1 (CDCP1) and Src dependent cell transformation. PloS one 12 23300860
2022 SRC kinase activator CDCP1 promotes hepatocyte growth factor-induced cell migration/invasion of a subset of breast cancer cells. The Journal of biological chemistry 11 35085554
2022 Molecular mechanism by which CDCP1 promotes proneural-mesenchymal transformation in primary glioblastoma. Cancer cell international 11 35410293
2024 Targeting CDCP1 boost CD8+ T cells-mediated cytotoxicity in cervical cancer via the JAK/STAT signaling pathway. Journal for immunotherapy of cancer 10 39455095
2023 Ascites-derived CDCP1+ extracellular vesicles subcluster as a novel biomarker and therapeutic target for ovarian cancer. Frontiers in oncology 10 37469398
2022 CDCP1: A promising diagnostic biomarker and therapeutic target for human cancer. Life sciences 10 35504333
2017 Inhibition of pulmonary carcinoma proliferation or metastasis of miR-218 via down-regulating CDCP1 expression. European review for medical and pharmacological sciences 10 28429357
2011 Effect of the tyrosine kinase inhibitor lapatinib on CUB-domain containing protein (CDCP1)-mediated breast cancer cell survival and migration. Biochemical and biophysical research communications 10 21945930
2021 CDCP1 promotes compensatory renal growth by integrating Src and Met signaling. Life science alliance 9 33574034
2015 The tyrosine phosphatase SHP2 associates with CUB domain-containing protein-1 (CDCP1), regulating its expression at the cell surface in a phosphorylation-dependent manner. PloS one 9 25876044
2006 Role of DNA methylation for expression of novel stem cell marker CDCP1 in hematopoietic cells. Leukemia 9 16926850
2023 Theranostic Targeting of CUB Domain-Containing Protein 1 (CDCP1) in Multiple Subtypes of Bladder Cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 8 36648492
2023 Mechanistic insights into CDCP1 clustering on non-small-cell lung cancer membranes revealed by super-resolution fluorescent imaging. iScience 8 36866248
2023 Inhibition of CDCP1 by 8-isopentenylnaringenin synergizes with EGFR inhibitors in lung cancer treatment. Molecular oncology 8 37013960
2020 The emerging role of the MiR-1272-ADAM9-CDCP1 signaling pathway in the progression of glioma. Aging 8 33260155
2015 The role of CDCP1 (CUB domain-containing protein 1) and ADAM12 (a disintegrin and metalloproteinase 12) in ovarian cancer. Journal of B.U.ON. : official journal of the Balkan Union of Oncology 8 26214617
2024 The CD318/CD6 axis limits type 1 diabetes islet autoantigen-specific human T cell activation. Journal of autoimmunity 7 38642507
2019 Effect of NLK on the proliferation and invasion of laryngeal carcinoma cells by regulating CDCP1. European review for medical and pharmacological sciences 7 31364124
2021 Preclinical Evaluation of a Fluorescent Probe Targeting Receptor CDCP1 for Identification of Ovarian Cancer. Molecular pharmaceutics 6 34448393
2018 CUB Domain-containing Protein 1 (CDCP1) Is Down-regulated by Active Hexose-correlated Compound in Human Pancreatic Cancer Cells. Anticancer research 6 30396925
2023 CDCP1 expression is frequently increased in aggressive urothelial carcinoma and promotes urothelial tumor progression. Scientific reports 5 36593286
2018 Evidence that cell surface localization of serine protease activity facilitates cleavage of the protease activated receptor CDCP1. Biological chemistry 5 29447112
2021 Preclinical Molecular PET-CT Imaging Targeting CDCP1 in Colorectal Cancer. Contrast media & molecular imaging 4 34621145
2019 Homophilic complex formation of CDCP1 via the extracellular CUB2 domain facilitates SFK activation and promotes cancer cell migration. Oncology reports 4 31524271
2023 CDCP1 (CUB domain containing protein 1) is a potential urine-based biomarker in the diagnosis of low-grade urothelial carcinoma. PloS one 3 36862682
2023 Erratum: Mechanistic insights into CDCP1 clustering on non-small-cell lung cancer membranes revealed by super-resolution fluorescent imaging. iScience 3 36942052
2021 Loss of CDCP1 triggers FAK activation in detached prostate cancer cells. American journal of clinical and experimental urology 3 34541033
2025 Receptor CDCP1 Is a Potential Target for Personalized Imaging and Treatment of Poor Outcome HER2+, Triple-Negative, and Metastatic ER+/HER2- Breast Cancers. Clinical cancer research : an official journal of the American Association for Cancer Research 2 39869307
2025 CDCP1 knockdown suppresses PDGFRβ/AKT pathway-mediated vascular smooth muscle cell proliferation by inhibiting PDGFRβ endocytosis. PeerJ 2 40256729
2025 Itolizumab regulates activating and inhibitory signals on effector cells, improving their cytotoxicity against CD318+ tumor cell lines. Frontiers in immunology 2 40391211
2025 CDCP1 promotes the malignant phenotypes of nasopharyngeal carcinoma via the Wnt/β-catenin signaling pathway. BMC biotechnology 2 40624715
2025 Proteomic Analysis of Extracellular Vesicles Identifies CDCP1 as Critical Metastasis-Related Glycoprotein in Lung Cancer. Journal of extracellular vesicles 2 40693605
2022 Cleaved CDCP1 marks the spot: a neoepitope for RAS-driven cancers. The Journal of clinical investigation 2 35166242

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