Affinage

Showing ACKR3 — CXCR7 is a alias.

ACKR3

Atypical chemokine receptor 3 · UniProt P25106

Length
362 aa
Mass
41.5 kDa
Annotated
2026-06-11
100 papers in source corpus 28 papers cited in narrative 28 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

ACKR3 (CXCR7) is an atypical, arrestin-biased chemokine receptor that functions principally as a ligand scavenger/decoy, regulating the extracellular availability of a broad set of peptide ligands rather than transmitting canonical G-protein signals (PMID:19380869, PMID:37558722). It binds CXCL12 and CXCL11 through distinct structural determinants—CXCL12 engaging transmembrane residues Asp-179 and Asp-275 while CXCL11 depends on the N-terminus and extracellular loops—and scavenges a cross-family ligand repertoire including opioid peptides (enkephalins, dynorphins), adrenomedullin and PAMP-12, and the viral chemokine vCCL2 (PMID:27875312, PMID:32561830, PMID:33860204, PMID:27238288). Although it constitutively associates with Gαi and undergoes ligand-induced conformational change, ACKR3 does not itself activate G proteins; instead its complete arrestin bias is structurally explained by arrestins being able to engage GRK-phosphorylated receptor even when excluded from the cytoplasmic core, whereas G proteins cannot (PMID:19380869, PMID:37558722, PMID:37502840). Receptor behavior is dictated by its C-terminal tail: tail phosphorylation by GRKs (with T352/S355 and GRK2/3 implicated in β-arrestin recruitment) drives β-arrestin association, constitutive internalization, predominant intracellular-vesicle localization, and recycling (PMID:22300987, PMID:33799570, PMID:37558722). In vivo, this scavenging activity controls systemic and local CXCL12 levels—endothelial ACKR3 sets plasma CXCL12 and limits leukocyte recruitment and breast cancer metastasis, and phosphorylation-dependent (but β-arrestin-independent) CXCL12 sequestration governs cortical interneuron migration by preventing CXCR4 overactivation (PMID:24116850, PMID:26119946, PMID:30726732). By scavenging adrenomedullin, ACKR3 controls cardiac and lymphatic vascular development (PMID:25203207). It forms heterodimers with CXCR4 that dampen CXCR4–Gαi signaling, and in disease contexts the ACKR3–β-arrestin complex scaffolds downstream effectors—activating ERK, Src, AKT, Aurora Kinase A, and Hippo/YAP signaling in cell-type- and context-dependent fashion (PMID:19380869, PMID:37347559, PMID:30804329, PMID:37950281). ACKR3 additionally has tissue-protective roles, restraining platelet activation and thrombosis and shaping splenic marginal-zone B-cell positioning (PMID:35383158, PMID:32755592).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 2009 High

    Established the defining paradox of ACKR3: it senses ligand and contacts G proteins yet does not signal through them, instead modulating a partner receptor.

    Evidence BRET/FRET energy transfer, calcium assays and primary T-cell experiments showing no Gαi activation and CXCR4 heterodimerization with impaired CXCR4 signaling

    PMID:19380869

    Open questions at the time
    • Did not resolve why G proteins fail to activate
    • Mechanism of heterodimer-mediated CXCR4 suppression not structurally defined
  2. 2012 High

    Localized the control of ACKR3 trafficking and scavenging to its C-terminal tail, linking intracellular localization to function.

    Evidence C-terminal deletion mutants with β-arrestin-2 complementation, scavenging, dynamin inhibition and ERK assays

    PMID:22300987

    Open questions at the time
    • Specific phosphorylation sites not yet mapped
    • Identity of GRKs acting on the tail not determined
  3. 2014 High

    Demonstrated in vivo that ACKR3 is a decoy receptor whose physiological output is regulating ligand dosage, both for adrenomedullin in development and for CXCL12 systemically.

    Evidence Cxcr7−/− mice with adrenomedullin epistasis rescue; endothelial knockout/pharmacology with plasma CXCL12 and leukocyte migration readouts

    PMID:24116850 PMID:25203207

    Open questions at the time
    • Cell-autonomous mechanism of ligand clearance not biochemically dissected
    • Relationship between developmental and systemic scavenging contexts unclear
  4. 2016 High

    Resolved that CXCL11 and CXCL12 bind ACKR3 through distinct determinants and that arrestin recruitment and scavenging are separable functions.

    Evidence Systematic site-directed mutagenesis (30 mutants) with radioligand binding, arrestin recruitment and scavenging assays

    PMID:27875312

    Open questions at the time
    • Structural basis of distinct binding modes not solved at this stage
    • How arrestin-independent scavenging proceeds not defined
  5. 2018 Medium

    Expanded the ligand and effector repertoire, identifying non-chemokine ligands (Dkk3, MIF) and downstream signaling cascades, and a CXCR4-heterodimer nuclear-arrestin oncogenic axis.

    Evidence Co-IP and saturation binding for Dkk3; MIF/AKT functional assays with CRISPR AR-site editing; co-IP plus transgenic mice for CXCR4 heterodimer/JMJD2A axis

    PMID:29980568 PMID:30224544 PMID:30337690

    Open questions at the time
    • Each ligand/effector shown in a single lab without cross-validation
    • Physiological versus disease-specific relevance of these signaling outputs unclear
  6. 2019 High

    Separated the in vivo requirement for receptor phosphorylation from β-arrestin, showing phosphorylation-dependent CXCL12 scavenging is the relevant activity for interneuron migration.

    Evidence Phosphorylation-deficient knock-in and β-arrestin-knockout mice with cortical migration, CXCL12 and CXCR4 degradation readouts

    PMID:30726732

    Open questions at the time
    • Which GRKs deposit the functional phosphomarks in vivo not identified
    • How phosphorylation drives scavenging independent of β-arrestin unresolved
  7. 2020 High

    Broadened ACKR3's scavenging scope across peptide families, establishing it as a regulator of opioid peptide availability with a selective pharmacological tool.

    Evidence Binding and scavenging assays plus in vivo rat brain experiments with the LIH383 competitor peptide

    PMID:32561830

    Open questions at the time
    • Endogenous regulatory weight of opioid-peptide scavenging in vivo not quantified
    • Tissue distribution of this activity not mapped
  8. 2021 High

    Mapped specific C-tail phosphorylation residues and GRK isoform requirements to β-arrestin recruitment, internalization and recycling, while revealing arrestin-independent internalization routes.

    Evidence BRET/FRET sensors with phosphosite mutants and GRK2/3/5 assays in HEK293T cells; agonist profiling of PAMP-12/adrenomedullin

    PMID:33799570 PMID:33860204

    Open questions at the time
    • Nature of alternative β-arrestin-independent internalization pathway undefined
    • Reconciliation of GRK2/3 versus GRK5/6 contributions across studies needed
  9. 2022 High

    Revealed protective tissue-level functions of ACKR3 in platelets/thrombosis and marginal-zone B-cell organization, distinct from its tumor-promoting roles.

    Evidence Cell-type-specific knockouts with ischemia models, lipidomics and pharmacological agonists; B-cell knockout with adoptive transfer rescue

    PMID:32755592 PMID:35383158

    Open questions at the time
    • Ligand driving platelet and B-cell phenotypes not fully defined
    • Link between scavenging and antithrombotic lipid generation mechanistically incomplete
  10. 2023 Medium

    Provided structural and comprehensive transducer-coupling explanations for ACKR3's complete arrestin bias and uncovered context-specific oncogenic effector scaffolding.

    Evidence Cryo-EM of ACKR3-arrestin complexes with GRK2/GRK5 barcodes (preprint); comprehensive coupling/conformational profiling; AURKA and Hippo/YAP mechanistic studies

    PMID:37347559 PMID:37502840 PMID:37558722 PMID:37950281

    Open questions at the time
    • Cryo-EM finding is a single unreviewed preprint
    • Disease-context effector pathways (AURKA, YAP) each rest on single-lab evidence

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single arrestin-biased scavenger integrates a broad ligand repertoire and GRK phospho-barcodes into the diverse, context-dependent downstream outputs (ERK, Src, AKT, AURKA, YAP) observed across tissues remains unresolved.
  • No unifying model linking phospho-barcode to specific effector output
  • Endogenous ligand hierarchy in any given tissue not established
  • Most disease-context signaling axes await independent confirmation

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0038024 cargo receptor activity 4 GO:0060089 molecular transducer activity 2 GO:0098772 molecular function regulator activity 2
Localization
GO:0031410 cytoplasmic vesicle 3 GO:0005768 endosome 2 GO:0005886 plasma membrane 2
Pathway
R-HSA-1643685 Disease 4 R-HSA-162582 Signal Transduction 3 R-HSA-168256 Immune System 3 R-HSA-1266738 Developmental Biology 2
Partners
ARRB1ARRB2AURKACXCR4DKK3GNAIGRK2GRK5
Complex memberships
ACKR3–CXCR4 heterodimerACKR3–β-arrestin complex

Evidence

Reading pass · 28 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2009 CXCR7 (ACKR3) does not trigger Gαi protein-dependent signaling by itself, despite constitutively interacting with Gαi proteins and undergoing CXCL12-mediated conformational changes as measured by energy transfer assays. When co-expressed with CXCR4, CXCR7 forms heterodimers as efficiently as homodimers and induces conformational rearrangements within preassembled CXCR4/Gαi protein complexes, impairing CXCR4-promoted Gαi-protein activation and calcium responses. BRET/FRET energy transfer assays, calcium mobilization assays, receptor co-expression studies in cell lines, primary T cell experiments with CXCL12/CXCR7 blocking Blood High 19380869
2012 The carboxy-terminal intracellular tail of CXCR7 controls receptor localization: wild-type CXCR7 predominantly localizes to intracellular vesicles, and progressive deletion of the C-terminus redistributes the receptor to the plasma membrane. C-tail truncations reduced chemokine scavenging, decreased basal and ligand-dependent β-arrestin-2 recruitment, impaired constitutive internalization, and reduced CXCL12-stimulated ERK1/2 activation. Inhibiting dynamin-dependent internalization enhanced ligand-dependent β-arrestin-2 association and ERK1/2 activation. C-terminal deletion mutants, firefly luciferase complementation assay for β-arrestin-2 recruitment, chemokine scavenging assays, dynamin inhibition, ERK phosphorylation assays The international journal of biochemistry & cell biology High 22300987
2016 Comprehensive mutational analysis of ACKR3 (30 substitution mutants) revealed distinct binding modes for CXCL11 and CXCL12: CXCL11 binding depends on the N-terminus and extracellular loop (ECL) positions for primary binding with ECL residues mediating secondary binding and arrestin recruitment potency; CXCL12 binding requires key residues Asp-179(4.60) and Asp-275(6.58) with no evident involvement of N-terminal residues. Mutation Q301E(7.39) abolished arrestin recruitment. Mutation K118A(3.26) in ECL1 showed constitutive arrestin recruitment with ablation of ligand-induced responses. Arrestin recruitment did not strictly correlate with chemokine scavenging. Site-directed mutagenesis, radioligand binding competition, arrestin recruitment assays, chemokine scavenging assays The Journal of biological chemistry High 27875312
2014 CXCR7 (ACKR3) acts as a decoy receptor for adrenomedullin (AM), controlling AM dosage and signaling during cardiovascular development. Cxcr7−/− mice exhibit gain-of-function cardiac and lymphatic vascular phenotypes that are reversed by genetic depletion of adrenomedullin ligand, establishing AM as a biological ligand whose availability is regulated by CXCR7. Genetic mouse knockout (Cxcr7−/−), genetic epistasis via double knockout with adrenomedullin, cardiac and lymphatic vascular phenotype analysis Developmental cell High 25203207
2019 ACKR3 phosphorylation (but not β-arrestin) is required for its control of CXCL12 levels in vivo and for proper interneuron migration in the embryonic cortex. Mice expressing phosphorylation-deficient ACKR3 showed a major interneuron migration defect accompanied by excessive CXCL12 accumulation, CXCR4 over-activation, and lysosomal CXCR4 degradation. β-arrestin-deficient mice showed only subtle migration defects mimicked by CXCR4 gain of function. Knock-in mice expressing phosphorylation-deficient ACKR3, β-arrestin knockout mice, in vivo cortical interneuron migration analysis, CXCL12 level measurements, CXCR4 degradation assays Cell reports High 30726732
2020 ACKR3/CXCR7 is a broad-spectrum scavenger receptor for opioid peptides, particularly enkephalins and dynorphins, reducing their availability for classical opioid receptors. An ACKR3-selective competitor peptide (LIH383) restrains ACKR3's negative regulatory function on opioid peptides in rat brain and potentiates their activity toward classical opioid receptors. ACKR3 is not modulated by prescription opioids. Binding assays, functional scavenging assays, in vitro peptide competition, in vivo rat brain experiments with LIH383 peptide competitor Nature communications High 32561830
2014 Endothelial CXCR7 regulates systemic circulating CXCL12 levels. Genetic deletion or pharmacological inhibition of CXCR7 caused pronounced increases in plasma CXCL12 levels, impairing leucocyte migration to a local CXCL12 source. CXCR7 protein was detected primarily on venule endothelium and arteriole smooth muscle cells in humans, and on venule endothelium in mice. Genetic knockout mouse, pharmacological inhibition, sensitive detection techniques for CXCR7 protein localization, plasma CXCL12 ELISA, leukocyte migration assays Immunology High 24116850
2023 Cryo-EM structures of arrestin-2 and arrestin-3 in complex with ACKR3 phosphorylated by GRK2 or GRK5 revealed that arrestin finger loops insert into the detergent/membrane rather than the receptor transmembrane core, unlike previously reported 'core' GPCR-arrestin complexes. GRK5 barcodes yield tighter complexes while GRK2 sites produce heterogeneous primarily 'tail-only' complexes. Arrestin-2 and -3 bind at different angles relative to the ACKR3 core due to differences in membrane anchoring at their C-edge loops. The 100% G protein bias (i.e., complete arrestin bias) of ACKR3 is structurally explained by the ability of arrestins, but not G proteins, to bind GRK-phosphorylated ACKR3 even when excluded from the cytoplasmic binding pocket. Cryo-electron microscopy structural determination of ACKR3-arrestin complexes, GRK2/GRK5 phosphorylation barcoding, novel Fab7 tool for structure determination bioRxivpreprint Medium 37502840
2021 ACKR3 C-tail phosphorylation regulates β-arrestin recruitment: residue T352 and in part S355 are important for β-arrestin-1 recruitment. GRK2 and GRK3 (but not GRK5) are key for β-arrestin recruitment and receptor internalization. Upon CXCL12 stimulation, ACKR3 internalizes and recycles to the cell membrane. ACKR3 can still internalize when β-arrestin recruitment is impaired or in the absence of β-arrestins, using alternative internalization pathways. BRET/FRET-based sensors in HEK293T cells, phosphorylation site mutants (WT and C-tail mutants), GRK2/3/5 recruitment assays, internalization and trafficking assays Cells High 33799570
2023 CXCR7 lacks G-protein coupling while maintaining robust β-arrestin recruitment with major contribution of GRK5/6. CXCR4 displays robust G-protein activation but significantly reduced β-arrestin coupling compared to CXCR7. These two receptors induce distinct β-arrestin conformations when activated by the same agonist (CXCL12 or VUF11207). CXCR7, unlike CXCR4, fails to activate ERK1/2 MAP kinase. A single phosphorylation site on CXCR7 is key for β-arrestin recruitment and endosomal localization. Comprehensive G-protein and β-arrestin coupling characterization, GRK isoform analysis, conformational biosensors, ERK assays, phosphorylation site mutagenesis Nature communications High 37558722
2018 Dickkopf-3 (Dkk3) is a novel binding partner and ligand for CXCR7. Co-immunoprecipitation from vascular Sca-1+ progenitor cell extracts showed physical interaction between Dkk3 and CXCR7; saturation binding assays identified a high-affinity Dkk3-CXCR7 binding with Kd of 14.14 nmol/L. Dkk3-CXCR7 binding triggered activation of ERK1/2, PI3K/AKT, Rac1, and RhoA signaling pathways mediating vascular progenitor cell migration. Co-immunoprecipitation, saturation binding assays, CXCR7 overexpression/knockdown, transwell migration assays, aortic ring assays, in vivo tissue-engineered vessel graft model with CXCR7 blocking antibodies Circulation research Medium 29980568
2016 HHV-8-encoded viral chemokine vCCL2/vMIP-II is a high-affinity agonist ligand for ACKR3, acting as a partial agonist that induces β-arrestin recruitment to the receptor, reduces ACKR3 surface levels, and delivers it to endosomes. ACKR3 scavenges vCCL2, reducing its availability for other chemokine receptors and attenuating vCCL2-triggered MAP kinase and PI3K/Akt signaling through those receptors. β-arrestin recruitment assays, flow cytometry for receptor surface levels, endosomal trafficking assays, MAP kinase/Akt signaling assays Biochemical pharmacology Medium 27238288
2021 Proadrenomedullin N-terminal 20 peptide (PAMP), especially PAMP-12, is a potent agonist of ACKR3, inducing β-arrestin recruitment and efficient internalization by ACKR3 without inducing G protein or ERK signaling in vitro. PAMP-12 had stronger potency toward ACKR3 than adrenomedullin itself. ADM was the only member of the CGRP family to show moderate ACKR3 activity. β-arrestin recruitment assays, internalization assays, G protein signaling assays, ERK signaling assays, comparison across CGRP family members ACS pharmacology & translational science Medium 33860204
2023 CXCR7 promotes neuroendocrine prostate cancer growth by activating Aurora Kinase A (AURKA) through β-arrestin 2 (ARRB2). The CXCR7-ARRB2 complex internalizes into clathrin-coated vesicles, traffics along microtubules to the pericentrosomal Golgi apparatus, where it interacts with and activates AURKA. CXCR7 interaction with AURKA promoted cell proliferation that was mitigated by AURKA inhibition. Co-immunoprecipitation, proximity ligation assays, subcellular trafficking/localization studies (microtubule and Golgi association), AURKA inhibitor treatment, in vitro proliferation and in vivo tumor growth assays The Journal of clinical investigation Medium 37347559
2018 CXCR7/CXCR4 heterodimers promote colorectal tumorigenesis through histone demethylation: the CXCR7/CXCR4 heterodimer induces nuclear β-arrestin-1 (βarr1) recruitment and histone demethylase JMJD2A expression, leading to histone demethylation and transcription of inflammatory factors and oncogenes. This was shown in human CRC tissues and transgenic mouse models (villin-CXCR7-CXCR4 mice showed greater tumorigenesis than single transgenic mice). Co-immunoprecipitation for heterodimer detection, transgenic mouse models, nuclear β-arrestin localization, JMJD2A expression and histone demethylation assays, human CRC tissue analysis Oncogene Medium 30337690
2019 CXCR7 activates the MAPK-ERK pathway via β-arrestin in EGFR TKI-resistant NSCLC cells with mesenchymal phenotype. Depletion of CXCR7 inhibited the MAPK pathway, attenuated EGFR TKI resistance, and resulted in mesenchymal-to-epithelial transition. CXCR7 overexpression was essential for ERK1/2 reactivation in persister cells. siRNA/shRNA knockdown, CXCR7 overexpression, ERK phosphorylation assays, drug resistance assays, EMT marker analysis in NSCLC cell lines Cancer research Medium 31273063
2015 Endothelial deletion of CXCR7 in adult mice (CXCR7ΔEND/ΔEND) resulted in modestly elevated plasma CXCL12 levels and significantly increased local breast cancer recurrence, elevated circulating tumor cells, and more spontaneous and experimental metastases, establishing that endothelial CXCR7 limits breast cancer metastasis by scavenging CXCL12. Conditional endothelial-specific knockout mouse model, orthotopic syngeneic tumor implant models, tumor recurrence and metastasis quantification, plasma CXCL12 measurement Oncogene High 26119946
2022 Megakaryocyte/platelet-specific deletion of ACKR3 results in enhanced platelet activation and thrombosis in vitro and in vivo, and increases tissue injury in ischemic myocardium and brain. Pharmacological ACKR3 agonists inhibit platelet activation and thrombus formation and attenuate tissue injury. ACKR3 ligation (via VUF11207) favors generation of antithrombotic lipids (DGLA, 12-HETrE) and coordinates with Gαs-coupled prostacyclin receptor via cAMP/PKA to inhibit platelets. Platelet/megakaryocyte-specific genetic knockout mouse, ischemia/reperfusion models (LAD ligation, tMCAO), targeted and untargeted lipidomics (MS/MS), pharmacological agonist treatment, flow cytometry Nature communications High 35383158
2022 Arterial endothelial ACKR3 deficiency attenuates atherosclerosis by reducing arterial adhesion and invasion of immune cells. ACKR3 silencing in inflamed human coronary artery endothelial cells decreased adhesion molecule expression and downregulated MAPK pathway mediators ERK1/2 and NF-κB p65 phosphorylation. Smooth muscle cell-specific or hematopoietic ACKR3 deficiency did not impact atherosclerosis. Cell-type specific conditional knockout mice (Apoe−/− background), siRNA silencing in human coronary artery endothelial cells, western diet atherosclerosis model, adhesion assays, ERK/NF-κB pathway analysis Basic research in cardiology Medium 35674847
2020 B cell-specific expression of ACKR3 is required for marginal zone (MZ) formation and positioning of MZ B cells in the spleen. Deletion of ACKR3 on B cells distorts the MZ, prevents MZ B cells from delivering antigens to follicles, and reduces humoral responses. ACKR3− MZ B cells can differentiate into ACKR3+ MZ B cells but not vice versa. Adoptive transfer experiments showed ACKR3-sufficient B cells, but not ACKR3-deficient B cells, can rescue MZ formation. B cell-specific ACKR3 knockout, adoptive transfer reconstitution experiments, splenic microarchitecture analysis, antigen delivery assays, T-independent antigen responses Cell reports High 32755592
2019 CXCR7 promotes melanoma cell proliferation through β-arrestin-2-dependent activation of Src kinase phosphorylation. The CXCR7-Src axis stimulates phosphorylation of eIF4E to accelerate translation of HIF-1α, which enhances VEGF secretion. Inhibition of Src kinase (PP1) or siRNA knockdown of β-arrestin-2 abolished CXCR7-promoted cell proliferation. CXCR7 knockout/overexpression, Src kinase inhibitor (PP1), β-arrestin-2 siRNA, eIF4E phosphorylation assays, HIF-1α translational assays, VEGF secretion assays, in vivo tumor growth models Cell death & disease Medium 30804329
2018 Macrophage migration inhibitory factor (MIF) is identified as a ligand for CXCR7 that induces cell-cycle gene expression through activating AKT signaling in castration-resistant prostate cancer (CRPC). The androgen receptor (AR) directly represses CXCR7 expression, and CXCR7 is upregulated after androgen deprivation therapy. CRISPR/Cas9 gene editing confirmed direct AR regulation of CXCR7. CRISPR/Cas9 AR binding site editing, MIF ligand-receptor functional assays, AKT pathway activation assays, CRPC cell line and patient specimen analysis Molecular cancer research : MCR Medium 30224544
2023 CXCR7 activation stimulates gastric cancer cell progression through the Hippo/YAP axis via G-protein Gαq/11 and Rho GTPase, leading to YAP dephosphorylation and nuclear accumulation. ChIP assays showed YAP binds to the CXCR7 promoter and facilitates its transcription, establishing a positive feedback loop between CXCR7 and Hippo/YAP. Immunoblotting, qPCR, xenograft models, ChIP assays for YAP binding to CXCR7 promoter, pharmacological CXCR7 inhibition (ACT-1004-1239), Gαq/11 and Rho GTPase pathway analysis Journal of experimental & clinical cancer research Medium 37950281
2012 CXCR7 (but not CXCR4) mediates SDF-1/CXCL12-induced melanocyte migration, with signaling mediated through β-arrestin-2-dependent ERK phosphorylation. Blocking CXCR4 with a neutralizing antibody did not affect SDF-1-induced melanocyte migration, whereas blocking CXCR7 did impair migration. Neutralizing antibody blockade of CXCR4 and CXCR7, ERK phosphorylation assays, β-arrestin-2 dependency assays, directional migration assays in normal human epidermal melanocytes Pigment cell & melanoma research Medium 22978759
2017 TGF-β1 upregulates CXCR7 expression in endothelial cells via a Smad2/3-dependent mechanism. CXCR7 overexpression attenuates TGF-β1-induced endothelial-to-mesenchymal transition (EndMT) by inhibiting the Jag1-Notch pathway, while CXCR7 knockdown further promotes EndMT. This represents a negative feedback mechanism restraining TGF-β-induced fibrosis. Smad2/3 pathway inhibition, CXCR7 overexpression and knockdown in lung endothelial cells, Jag1-Notch pathway analysis, EndMT marker analysis, mouse lung fibrosis model Molecular bioSystems Medium 28820530
2019 FGFR3 deficiency in myeloid cells promotes macrophage chemotaxis via NF-κB-dependent upregulation of CXCR7. Neutralizing antibody against CXCR7 significantly reversed FGFR3-deficiency-enhanced macrophage chemotaxis and the arthritic phenotype in Cxcr7 knockout mice (R3cKO). Conditional myeloid FGFR3 knockout mice, RNA-seq, western blotting, chemotaxis assays, CXCR7 neutralizing antibody treatment, NF-κB pathway analysis, DMM arthritis model Annals of the rheumatic diseases Medium 31662319
2014 CXCR7 acts as a scavenger receptor in OPC (oligodendrocyte progenitor cell) maturation during remyelination: in vivo CXCR7 antagonism augmented OPC proliferation and increased mature oligodendrocyte numbers in demyelinated lesions. CXCR7-mediated effects on remyelination required CXCR4 activation (tested with phospho-CXCR4 antibodies and CXCR4 antagonists), establishing CXCR7 as a regulator of available CXCL12 for CXCR4-driven OPC maturation. Cuprizone-induced demyelination model, small molecule CXCR7 antagonist in vivo, CXCR4 antagonists, phospho-S339-CXCR4-specific antibodies, OPC quantification The Journal of experimental medicine Medium 24733828
2015 CXCR7 promotes angiogenic properties of tumor endothelial cells (TECs) via ERK1/2 phosphorylation. CXCR7 siRNA and CXCR7 inhibitor (CCX771) inhibited migration, tube formation, and survival in serum starvation in TECs but not normal endothelial cells. An autocrine CXCL12-CXCR7 loop was identified in TECs (CXCL12 detected in conditioned medium from TECs but not NECs). VEGF upregulated CXCR7 expression in endothelial cells. siRNA knockdown, pharmacological inhibitor (CCX771), ERK1/2 phosphorylation assays, ELISA for CXCL12, migration and tube formation assays, in vivo tumor growth/angiogenesis International journal of cancer Medium 26100110

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 CXCL12 / CXCR4 / CXCR7 chemokine axis and cancer progression. Cancer metastasis reviews 608 20839032
2009 CXCR7 heterodimerizes with CXCR4 and regulates CXCL12-mediated G protein signaling. Blood 507 19380869
2011 CXCL12 (SDF1alpha)-CXCR4/CXCR7 pathway inhibition: an emerging sensitizer for anticancer therapies? Clinical cancer research : an official journal of the American Association for Cancer Research 343 21349998
2020 The Role of the CXCL12/CXCR4/CXCR7 Chemokine Axis in Cancer. Frontiers in pharmacology 243 33363463
2010 Hypoxic preconditioning advances CXCR4 and CXCR7 expression by activating HIF-1α in MSCs. Biochemical and biophysical research communications 206 20869949
2008 CXCR7, CXCR4 and CXCL12: an eccentric trio? Journal of neuroimmunology 199 18533280
2019 The CXCL12-CXCR4/CXCR7 axis as a mechanism of immune resistance in gastrointestinal malignancies. Seminars in cancer biology 196 31874281
2023 CXCL12-CXCR4/CXCR7 Axis in Cancer: from Mechanisms to Clinical Applications. International journal of biological sciences 175 37497001
2012 CXCR7 impact on CXCL12 biology and disease. Trends in molecular medicine 175 23153575
2012 Chemokine receptor trio: CXCR3, CXCR4 and CXCR7 crosstalk via CXCL11 and CXCL12. Cytokine & growth factor reviews 165 22989616
2014 CXCL12 modulation of CXCR4 and CXCR7 activity in human glioblastoma stem-like cells and regulation of the tumor microenvironment. Frontiers in cellular neuroscience 150 24904289
2019 The Role of the CXCL12/CXCR4/ACKR3 Axis in Autoimmune Diseases. Frontiers in endocrinology 136 31507535
2017 The Role of SDF-1/CXCR4/CXCR7 in Neuronal Regeneration after Cerebral Ischemia. Frontiers in neuroscience 107 29123467
2009 The role of stromal-derived factor-1--CXCR7 axis in development and cancer. European journal of pharmacology 104 19835865
2013 Involvement of CXCR4/CXCR7/CXCL12 Interactions in Inflammatory bowel disease. Theranostics 98 23382785
2020 The atypical chemokine receptor ACKR3/CXCR7 is a broad-spectrum scavenger for opioid peptides. Nature communications 97 32561830
2012 An infernal trio: the chemokine CXCL12 and its receptors CXCR4 and CXCR7 in tumor biology. Annals of anatomy = Anatomischer Anzeiger : official organ of the Anatomische Gesellschaft 87 23279723
2014 Decoy receptor CXCR7 modulates adrenomedullin-mediated cardiac and lymphatic vascular development. Developmental cell 82 25203207
2021 CXCR4 and CXCR7 Signaling Pathways: A Focus on the Cross-Talk Between Cancer Cells and Tumor Microenvironment. Frontiers in oncology 81 33937018
2014 Endothelial expression of CXCR7 and the regulation of systemic CXCL12 levels. Immunology 77 24116850
2018 CXCR7 Targeting and Its Major Disease Relevance. Frontiers in pharmacology 75 29977203
2009 CXCL12, CXCR4 and CXCR7 expression in brain metastases. Cancer biology & therapy 72 19625779
2010 Activation of CXCR7 receptor promotes oligodendroglial cell maturation. Annals of neurology 67 21154415
2020 Relevance of the CXCR4/CXCR7-CXCL12 axis and its effect in pathophysiological conditions. Pharmacological research 66 32758634
2020 The CXCL12/CXCR4/ACKR3 Axis in the Tumor Microenvironment: Signaling, Crosstalk, and Therapeutic Targeting. Annual review of pharmacology and toxicology 65 32956018
2019 ACKR3 Regulation of Neuronal Migration Requires ACKR3 Phosphorylation, but Not β-Arrestin. Cell reports 65 30726732
2017 CXCL12 and CXCR7 are relevant targets to reverse cell adhesion-mediated drug resistance in multiple myeloma. British journal of haematology 65 28670693
2015 CXCL12-CXCR7 axis is important for tumor endothelial cell angiogenic property. International journal of cancer 65 26100110
2017 Biological/pathological functions of the CXCL12/CXCR4/CXCR7 axes in the pathogenesis of bladder cancer. International journal of clinical oncology 64 29022185
2015 Crosstalk between SDF-1/CXCR4 and SDF-1/CXCR7 in cardiac stem cell migration. Scientific reports 59 26578388
2018 Multisystem multitasking by CXCL12 and its receptors CXCR4 and ACKR3. Cytokine 58 29398278
2019 FGFR3 deficiency enhances CXCL12-dependent chemotaxis of macrophages via upregulating CXCR7 and aggravates joint destruction in mice. Annals of the rheumatic diseases 56 31662319
2014 Targeting CXCR7/ACKR3 as a therapeutic strategy to promote remyelination in the adult central nervous system. The Journal of experimental medicine 56 24733828
2019 CXCR7 Reactivates ERK Signaling to Promote Resistance to EGFR Kinase Inhibitors in NSCLC. Cancer research 53 31273063
2019 LPS-induced CXCR7 expression promotes gastric Cancer proliferation and migration via the TLR4/MD-2 pathway. Diagnostic pathology 51 30636642
2018 A Chimeric Antibody against ACKR3/CXCR7 in Combination with TMZ Activates Immune Responses and Extends Survival in Mouse GBM Models. Molecular therapy : the journal of the American Society of Gene Therapy 51 29606504
2018 Emerging roles of atypical chemokine receptor 3 (ACKR3) in normal development and physiology. Cytokine 51 29903572
2019 Modulators of CXCR4 and CXCR7/ACKR3 Function. Molecular pharmacology 50 31548340
2015 Endothelial CXCR7 regulates breast cancer metastasis. Oncogene 50 26119946
2016 Expression and function of CXCL12/CXCR4/CXCR7 in thyroid cancer. International journal of oncology 49 27082011
2019 Atypical Chemokine Receptor 3 (ACKR3): A Comprehensive Overview of its Expression and Potential Roles in the Immune System. Molecular pharmacology 48 31040166
2021 Role and implications of the CXCL12/CXCR4/CXCR7 axis in atherosclerosis: still a debate. Annals of medicine 46 34494495
2017 CXCR7 attenuates the TGF-β-induced endothelial-to-mesenchymal transition and pulmonary fibrosis. Molecular bioSystems 46 28820530
2016 Mutational Analysis of Atypical Chemokine Receptor 3 (ACKR3/CXCR7) Interaction with Its Chemokine Ligands CXCL11 and CXCL12. The Journal of biological chemistry 44 27875312
2013 CXCR7 is induced by hypoxia and mediates glioma cell migration towards SDF-1α. BMC cancer 44 23865743
2019 The Role of ACKR3 in Breast, Lung, and Brain Cancer. Molecular pharmacology 42 30745320
2011 Expression of the new CXCL12 receptor, CXCR7, in gliomas. Cancer biology & therapy 42 21084856
2022 ACKR3 regulates platelet activation and ischemia-reperfusion tissue injury. Nature communications 41 35383158
2018 Targeting the MIF/CXCR7/AKT Signaling Pathway in Castration-Resistant Prostate Cancer. Molecular cancer research : MCR 41 30224544
2014 The relevance of the chemokine receptor ACKR3/CXCR7 on CXCL12-mediated effects in cancers with a focus on virus-related cancers. Cytokine & growth factor reviews 41 24853339
2012 CXCR7 mediates SDF1-induced melanocyte migration. Pigment cell & melanoma research 41 22978759
2019 Antibodies Targeting Chemokine Receptors CXCR4 and ACKR3. Molecular pharmacology 40 31481460
2018 Binding of Dickkopf-3 to CXCR7 Enhances Vascular Progenitor Cell Migration and Degradable Graft Regeneration. Circulation research 40 29980568
2016 Drug Design Targeting the CXCR4/CXCR7/CXCL12 Pathway. Current topics in medicinal chemistry 39 26369824
2016 CXCR4 and CXCR7 Mediate TFF3-Induced Cell Migration Independently From the ERK1/2 Signaling Pathway. Investigative ophthalmology & visual science 39 26780310
2022 Colorectal Cancer: The Contribution of CXCL12 and Its Receptors CXCR4 and CXCR7. Cancers 38 35406582
2015 Role of chemokine receptors CXCR4 and CXCR7 for platelet function. Biochemical Society transactions 38 26551719
2011 Expression of CXCR7 chemokine receptor in human meningioma cells and in intratumoral microvasculature. Journal of neuroimmunology 38 21316111
2012 Carboxy-terminus of CXCR7 regulates receptor localization and function. The international journal of biochemistry & cell biology 37 22300987
2018 CXCR7/CXCR4 heterodimer-induced histone demethylation: a new mechanism of colorectal tumorigenesis. Oncogene 36 30337690
2011 The expression of CXCR4, CXCL12 and CXCR7 in malignant pleural mesothelioma. The Journal of pathology 36 21294125
2022 Platelet ACKR3/CXCR7 favors antiplatelet lipids over an atherothrombotic lipidome and regulates thromboinflammation. Blood 35 34905596
2016 Human herpesvirus 8-encoded chemokine vCCL2/vMIP-II is an agonist of the atypical chemokine receptor ACKR3/CXCR7. Biochemical pharmacology 35 27238288
2022 Endothelial ACKR3 drives atherosclerosis by promoting immune cell adhesion to vascular endothelium. Basic research in cardiology 33 35674847
2021 Differential Involvement of ACKR3 C-Tail in β-Arrestin Recruitment, Trafficking and Internalization. Cells 33 33799570
2020 Advances in CXCR7 Modulators. Pharmaceuticals (Basel, Switzerland) 33 32098047
2016 Drug design strategies focusing on the CXCR4/CXCR7/CXCL12 pathway in leukemia and lymphoma. Expert opinion on drug discovery 33 27598329
2014 CXCR7-dependent angiogenic mononuclear cell trafficking regulates tumor progression in multiple myeloma. Blood 33 25079359
2013 CXCR7 expression in esophageal cancer. Journal of translational medicine 32 24074251
2012 Expression of stromal cell-derived factor 1 and CXCR7 in papillary thyroid carcinoma. Endocrine pathology 31 23070788
2022 Emerging Roles of the Atypical Chemokine Receptor 3 (ACKR3) in Cardiovascular Diseases. Frontiers in endocrinology 30 35846294
2017 CXCR7 regulates breast tumor metastasis and angiogenesis in vivo and in vitro. Molecular medicine reports 29 29257351
2021 Proadrenomedullin N-Terminal 20 Peptides (PAMPs) Are Agonists of the Chemokine Scavenger Receptor ACKR3/CXCR7. ACS pharmacology & translational science 28 33860204
2016 Targeted Imaging of the Atypical Chemokine Receptor 3 (ACKR3/CXCR7) in Human Cancer Xenografts. Journal of nuclear medicine : official publication, Society of Nuclear Medicine 28 26912435
2016 CXCR7 Participates in CXCL12-mediated Cell Cycle and Proliferation Regulation in Mouse Neural Progenitor Cells. Current molecular medicine 28 27573194
2023 Molecular insights into intrinsic transducer-coupling bias in the CXCR4-CXCR7 system. Nature communications 27 37558722
2019 CXCR7 promotes migration and invasion in head and neck squamous cell carcinoma by upregulating TGF-β1/Smad2/3 signaling. Scientific reports 27 31792315
2015 Targeting chemokine receptor CXCR7 inhibits glioma cell proliferation and mobility. Anticancer research 27 25550535
2019 CXCR7 promotes melanoma tumorigenesis via Src kinase signaling. Cell death & disease 26 30804329
2024 Crosstalk between CXCL12/CXCR4/ACKR3 and the STAT3 Pathway. Cells 25 38920657
2020 Functions of the CXCL12 Receptor ACKR3/CXCR7-What Has Been Perceived and What Has Been Overlooked. Molecular pharmacology 24 32883765
2023 Chemokine receptor CXCR7 activates Aurora Kinase A and promotes neuroendocrine prostate cancer growth. The Journal of clinical investigation 23 37347559
2023 Regulation of the Hippo/YAP axis by CXCR7 in the tumorigenesis of gastric cancer. Journal of experimental & clinical cancer research : CR 23 37950281
2018 CXCR7 participates in CXCL12-mediated migration and homing of leukemic and normal hematopoietic cells. Stem cell research & therapy 23 29433559
2020 Overexpression of CXCR7 accelerates tumor growth and metastasis of lung cancer cells. Respiratory research 22 33129326
2018 CXCR4/CXCR7/CXCL12-Axis in Follicular Thyroid Carcinoma. Journal of Cancer 22 29581772
2017 Astrocytic expression of the CXCL12 receptor, CXCR7/ACKR3 is a hallmark of the diseased, but not developing CNS. Molecular and cellular neurosciences 22 28889992
2023 CXCR7 as a novel therapeutic target for advanced prostate cancer. Oncogene 21 36755058
2020 Inhibition of CXCR4 and CXCR7 Is Protective in Acute Peritoneal Inflammation. Frontiers in immunology 21 32210974
2014 Chemokine receptor CXCR7 is a functional receptor for CXCL12 in brain endothelial cells. PloS one 21 25084358
2023 ACKR3-arrestin2/3 complexes reveal molecular consequences of GRK-dependent barcoding. bioRxiv : the preprint server for biology 20 37502840
2021 CXCR7 Antagonism Reduces Acute Lung Injury Pathogenesis. Frontiers in pharmacology 20 34803691
2020 CXCR4 or CXCR7 antagonists treat endometriosis by reducing bone marrow cell trafficking. Journal of cellular and molecular medicine 20 31904910
2020 The expression and biological function of chemokine CXCL12 and receptor CXCR4/CXCR7 in placenta accreta spectrum disorders. Journal of cellular and molecular medicine 20 31991051
2018 CXCR7/ACKR3-targeting ligands interfere with X7 HIV-1 and HIV-2 entry and replication in human host cells. Heliyon 20 29560468
2015 Co-expression of CXCR4 and CXCR7 in human endometrial stromal cells is modulated by steroid hormones. International journal of clinical and experimental pathology 20 26045751
2021 CXCR4 and CXCR7 Inhibition Ameliorates the Formation of Platelet-Neutrophil Complexes and Neutrophil Extracellular Traps through Adora2b Signaling. International journal of molecular sciences 19 34948374
2015 Expression and functional roles of the chemokine receptor CXCR7 in acute myeloid leukemia cells. Blood research 19 26770949
2024 Single-cell RNA sequencing reveals the MIF/ACKR3 receptor-ligand interaction between neutrophils and nucleus pulposus cells in intervertebral disc degeneration. Translational research : the journal of laboratory and clinical medicine 18 38823438
2020 Marginal Zone Formation Requires ACKR3 Expression on B Cells. Cell reports 18 32755592

Missed literature

Know a paper Affinage missed for ACKR3? Flag it for the maintainers and the community.

No submissions yet.