Affinage

RECK

Reversion-inducing cysteine-rich protein with Kazal motifs · UniProt O95980

Length
971 aa
Mass
106.5 kDa
Annotated
2026-06-10
100 papers in source corpus 31 papers cited in narrative 31 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RECK is a GPI-anchored membrane glycoprotein with two distinct biological roles: it is a multi-target inhibitor of pericellular proteolysis and a Wnt7a/Wnt7b-selective co-receptor that transduces CNS-specific Wnt/β-catenin signaling (PMID:12784995, PMID:28803732, PMID:30304675). As a protease regulator, RECK negatively controls MMP-2, MMP-9, and MT1-MMP activity, and its loss is embryonic-lethal with elevated MMP activity and ECM (collagen) deficits that are partially rescued by concurrent MMP-2 ablation, establishing a functional RECK–MMP-2 axis in vivo (PMID:12784995). RECK acts on MMPs at multiple levels — direct inhibition of MMP-2 activation and MMP-9 secretion through site-specific N-glycosylation (Asn297, Asn352) (PMID:16103099), post-translational suppression of MMP-9 enzymatic activity (PMID:35892136), and transcriptional repression of MMP-9 by reducing Fra-1/c-Jun occupancy of the AP-1/κB sites in its promoter (PMID:19208844). Through this proteolytic control RECK restrains tumor cell invasion and metastasis: pancreatic Reck deletion drives mesenchymal PDAC with EMT and liver metastasis, while re-expression downregulates MMP2/MMP3, restores E-cadherin, and is phenocopied by MMP inhibition (PMID:37712427). RECK additionally enforces a cell-cycle brake by downregulating SKP2 and stabilizing p27(KIP1) (PMID:22158033). In its second role, RECK directly binds WNT7A and WNT7B (not WNT3A) at 1:1 stoichiometry, stabilizing the active monomeric ligand, and assembles with GPR124 — via its N-terminal CC1 domain binding the GPR124 LRR/Ig ectodomain — together with Frizzled to form a tripartite cell-surface complex that drives canonical Wnt signaling for brain angiogenesis and blood-brain barrier formation (PMID:28803732, PMID:30304675, PMID:26051822, PMID:26657775). Discrete CC4 residues (P256, W261) are required for WNT7A stimulation, and this WNT7/GPR124/RECK module also operates outside the CNS in limb development (PMID:31225798, PMID:35552394). RECK shedding by GDE2 relieves its inhibition of ADAM10-dependent APP cleavage, linking elevated membrane RECK to impaired α-secretase processing in Alzheimer's disease (PMID:33731436). RECK is transcriptionally repressed by oncogenic ERK/Sp1 signaling (PMID:14614450) and by multiple miRNAs (miR-15b/16, miR-21, miR-372/373, miR-92a) downstream of hypoxia, RAS, and STAT3 (PMID:20154725, PMID:23820254), and is induced by TIMP-2 through a Rap1 cascade and by HDAC inhibition (PMID:15604273, PMID:12810630).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 2003 High

    Established RECK as a physiologically essential, membrane-anchored MMP inhibitor rather than an in vitro curiosity, by showing its loss is lethal through unleashed proteolysis.

    Evidence Reck-null mice with genetic epistasis against MMP-2-null and in vitro MMP activity assays

    PMID:12784995

    Open questions at the time
    • Did not resolve which MMP interactions are direct enzymatic inhibition versus indirect
    • Mechanism of ECM/collagen protection not separated from MMP activity
  2. 2003 Medium

    Defined how RECK is silenced in cancer and how it can be pharmacologically restored, linking ERK/Sp1 promoter repression and HDAC-inhibitor induction to invasive phenotypes.

    Evidence TSA induction and siRNA rescue in lung cancer; LMP1/ERK/Sp1 promoter reporter and invasion assays

    PMID:12810630 PMID:14614450

    Open questions at the time
    • Single-lab transcriptional studies
    • Direct Sp1 occupancy versus indirect effects not fully dissected
  3. 2004 High

    Identified an inducible, MMP-inhibition-independent signaling route (TIMP-2→Rap1) that upregulates RECK to suppress endothelial migration, defining RECK as a downstream effector of TIMP-2.

    Evidence Rap1 overexpression, RECK-null cells, anti-RECK antibody, Crk/C3G Co-IP, migration assays; later refined to a Src/Csk/paxillin switch

    PMID:15604273 PMID:16491114

    Open questions at the time
    • How Rap1 signaling reaches the RECK promoter not defined
    • Src/paxillin switch model is single-lab Co-IP based
  4. 2005 High

    Mapped the post-translational requirement for RECK function by showing specific N-glycosylation sites are differentially required to block MMP-2 versus MMP-9.

    Evidence Site-directed mutagenesis of Asn residues with zymography and invasion assays in HT1080

    PMID:16103099

    Open questions at the time
    • No structural basis for how glycans confer protease selectivity
    • Single cell-line context
  5. 2009 Medium

    Extended RECK's repertoire beyond direct protease inhibition to transcriptional MMP-9 repression and revealed opposing RECK/MT1-MMP roles in progenitor motility in vivo.

    Evidence MMP-9 promoter reporter, ChIP and siRNA; anti-RECK/anti-MT1-MMP antibody and NOD/SCID mobilization model

    PMID:19197139 PMID:19208844

    Open questions at the time
    • Mechanism linking surface RECK to nuclear AP-1 occupancy unresolved
    • G-CSF/PI3K control of RECK shown only in progenitor context
  6. 2010 High

    Showed convergent post-transcriptional silencing of RECK by oncogenic and hypoxic pathways through specific miRNAs, explaining loss of RECK in tumors without promoter mutation.

    Evidence 3'UTR luciferase reporters with target-site mutagenesis, HIF1α/TWIST1/RAS manipulation, tumor-suppression assays

    PMID:20154725

    Open questions at the time
    • Relative contribution of each miRNA in vivo not quantified
    • Did not address whether de-repression alone restores tumor suppression
  7. 2010 Medium

    Connected RECK to non-tumor physiology — ischemic ECM protection, vascular lumen morphogenesis, and OA chondrocyte adhesion — broadening its role to tissue integrity and cell shape.

    Evidence Reck+/- ischemia model with LTP/zymography; conditional KO/shRNA angiogenesis; chondrocyte KD/OE with FAK/ERK readouts

    PMID:20395433 PMID:20691046 PMID:20796170

    Open questions at the time
    • Whether vascular and ECM phenotypes are purely MMP-mediated unclear
    • Single-lab phenotypic studies
  8. 2011 Medium

    Identified a proteolysis-independent growth-suppressive arm of RECK acting through the SKP2–p27 cell-cycle axis.

    Evidence Acute RECK expression, cell-cycle analysis, SKP2/p27 westerns and p27-dependence rescue in colon carcinoma

    PMID:22158033

    Open questions at the time
    • How surface RECK signals to SKP2 not defined
    • p27-independent component not characterized
  9. 2012 High

    Revealed a developmental, signaling role for Reck in neural crest by showing cell-autonomous requirement for sensory neuron migration to the DRG.

    Evidence Zebrafish forward screen, four independent reck alleles, rescue and mosaic cell-autonomy analysis

    PMID:22296847

    Open questions at the time
    • Molecular pathway downstream of Reck in neural crest not yet linked to Wnt at this stage
  10. 2015 High

    Repositioned RECK as a core component of a Wnt7a/7b-GPR124 signaling complex selectively driving CNS angiogenesis, BBB formation, and tip-cell function.

    Evidence Zebrafish forward genetics, endothelial Wnt reporters, mosaic single-cell rescue and live imaging

    PMID:26051822 PMID:26657775

    Open questions at the time
    • Biochemical composition of the receptor complex not yet defined at this stage
    • VEGF cascade involvement only correlative in culture
  11. 2017 High

    Defined the architecture of the Wnt7 signaling complex by mapping the RECK CC1–GPR124 ectodomain interaction and demonstrating a tripartite Frizzled/Wnt7/RECK/GPR124 surface assembly required for CNS vasculature.

    Evidence EC-specific conditional KO, CC1 domain mutagenesis, soluble-probe cell-binding assays, Wnt reporters

    PMID:28803732

    Open questions at the time
    • Stoichiometry of the full complex not resolved here
    • How the complex couples to β-catenin not detailed
  12. 2018 High

    Demonstrated direct, selective biochemistry — RECK binds WNT7A/7B at 1:1 to stabilize the active ligand — and identified GPR124 as RECK's predominant in situ vascular partner.

    Evidence Purified recombinant binding assays, chemical cross-linking stoichiometry, in situ rat brain vessel binding, truncated GPR124 reporters

    PMID:30304675

    Open questions at the time
    • Structure of the RECK–WNT7 interface not solved
    • How ligand stabilization is handed to Frizzled mechanistically unclear
  13. 2018 Medium

    Uncovered a regulatory short RECK isoform that antagonizes canonical RECK by competing MMP9 off its Kazal motifs, revealing isoform-level tuning of protease inhibition.

    Evidence Isoform-specific siRNA, migration assays, competitive MMP9-binding assay on canonical RECK Kazal motifs

    PMID:29874120

    Open questions at the time
    • Physiological regulation of isoform ratio unknown
    • Single-lab competitive binding model
  14. 2019 High

    Pinpointed the ligand- and receptor-side determinants of Wnt7 selectivity, identifying RECK CC4 residues (P256, W261) essential for signaling and CNS angiogenesis without affecting trafficking.

    Evidence Mutagenesis of Reck CC4 and Wnt7a residues, Wnt reporters, surface localization, mouse embryo phenotyping

    PMID:31225798

    Open questions at the time
    • How CC1 (GPR124 binding) and CC4 (Wnt7 function) cooperate not structurally resolved
  15. 2021 High

    Linked RECK shedding to neurodegeneration by showing GDE2-mediated release of GPI-anchored RECK is required to permit ADAM10 α-secretase cleavage of APP.

    Evidence GDE2 KO mice, RECK-reduction rescue, sAPPα/Aβ and synaptic protein measurements, biochemical fractionation

    PMID:33731436

    Open questions at the time
    • Direct RECK–ADAM10 inhibition kinetics not quantified
    • Why RECK is elevated in human AD mechanistically unclear
  16. 2022 High

    Generalized the WNT7/GPR124/RECK module beyond the CNS by showing it is required for mammalian limb bone growth and patterning.

    Evidence Combinatorial conditional KOs and a Wnt7-signaling-defective Reck knock-in allele with limb phenotyping

    PMID:35552394

    Open questions at the time
    • Tissue source of Wnt7 ligands and complex partners in limb not fully mapped
  17. 2023 High

    Provided definitive in vivo evidence that RECK loss promotes EMT, mesenchymal PDAC, and metastasis through MMP-dependent ECM remodeling, with re-expression rescuing the epithelial state.

    Evidence Pancreatic conditional Reck KO, lineage tracing, splenic transplant metastasis model, RECK re-expression, MMP-inhibitor epistasis

    PMID:37712427

    Open questions at the time
    • Whether the Wnt7 signaling arm contributes to the PDAC phenotype not addressed
    • Identity of all relevant MMP substrates not defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • A unified structural and mechanistic account of how one GPI-anchored protein both inhibits diverse proteases (MMPs, ADAM10) and serves as a Wnt7-selective co-receptor — including whether these functions are spatially or isoform-segregated — remains unresolved.
  • No atomic structure of RECK or its complexes
  • Functional crosstalk between MMP-inhibition and Wnt-signaling domains untested
  • GRP78/ER-stress role rests on a single low-confidence report (#25)

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 4 GO:0098772 molecular function regulator activity 4 GO:0140096 catalytic activity, acting on a protein 3
Localization
GO:0005886 plasma membrane 4
Pathway
R-HSA-1266738 Developmental Biology 3 R-HSA-1474244 Extracellular matrix organization 3 R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 2
Partners
ADAM10GDE2GPR124MMP2MMP9TIMP2WNT7AWNT7B
Complex memberships
WNT7A/7B–GPR124–Frizzled–RECK signaling complex

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 RECK was identified as a membrane-anchored GPI-anchored glycoprotein that negatively regulates MMP-2, MMP-9, and MT1-MMP activities. Mice lacking RECK die in utero with elevated MMP activity and reduced collagen type I; this lethal phenotype is partially rescued by MMP-2 null mutation, demonstrating functional interaction between RECK and MMP-2 in vivo. Gene knockout mouse model, genetic epistasis (Reck-null × MMP-2-null double mutant), in vitro MMP activity assays Cancer metastasis reviews High 12784995
2003 HDAC inhibitor trichostatin A (TSA) up-regulates RECK transcriptionally in human lung cancer cells, increases cell-surface RECK protein, attenuates MMP-2 activity, and suppresses invasion. siRNA knockdown of RECK abolishes the TSA-mediated inhibition of MMP-2 activation, establishing RECK as the mediating effector. siRNA knockdown, flow cytometry, gelatin zymography, invasion assay, transcriptional activation assay Cancer research Medium 12810630
2003 EBV latent membrane protein 1 (LMP1) represses RECK expression via the ERK/Sp1 signaling pathway, acting through an Sp1 site in the RECK promoter. This RECK suppression is required for LMP1-induced release of active MMP-9 and increased tumor cell invasiveness; re-expression of RECK or inhibition of ERK reverses these effects. Promoter reporter assay, ERK inhibitor (PD98059), siRNA, invasion assay, conditioned medium zymography Oncogene Medium 14614450
2004 TIMP-2 (but not TIMP-1, and including MMP-inhibitory-dead Ala+TIMP-2) inhibits endothelial cell migration by inducing RECK expression via a Rap1-signaling pathway: TIMP-2 increases Crk–C3G association, activates Rap1, and upregulates RECK, which in turn decreases cell-associated MMP activity. Anti-RECK antibody restores MMP activity and reverses TIMP-2-mediated reduction in migration. RECK-null fibroblasts fail to show TIMP-2-mediated migration inhibition despite Rap1 activation. Stable Rap1 overexpression, RECK-null cells, anti-RECK antibody, Co-IP of Crk/C3G, zymography, migration assay Cancer research High 15604273
2005 RECK protein is N-glycosylated at Asn86, Asn200, Asn297, and Asn352 (but not Asn39) in HT1080 cells. Glycosylation at Asn297 is required for suppression of MMP-9 secretion, glycosylation at Asn352 is required for inhibition of MMP-2 activation, and glycosylation at Asn86, Asn297, and Asn352 collectively mediates RECK-dependent suppression of tumor cell invasion. Site-directed mutagenesis of N-glycosylation sites, zymography, invasion assay Cancer research High 16103099
2006 TIMP-2 upregulates RECK via a signaling cascade in which TIMP-2 binding activates Csk-mediated phosphorylation of Src at Tyr-527 (inhibitory), reducing Src kinase activity and causing dephosphorylation of paxillin at Tyr-31/118, which switches signaling from the Rac1 pathway (via paxillin-Crk-DOCK180) to the Rap1 pathway (via paxillin-Crk-C3G), thereby enhancing RECK expression. Phospho-specific western blotting, Co-IP of Src/Csk and paxillin complexes, dominant-negative Rap1 Oncogene Medium 16491114
2009 RECK transcriptionally suppresses MMP-9 by reducing the binding of Fra-1 and c-Jun to the TRE (AP-1) and κB sites in the MMP-9 promoter. RECK overexpression in HT1080 cells decreases MMP-9 mRNA, and siRNA-mediated RECK knockdown increases MMP-9 mRNA in RECK-expressing cells. Gene expression profiling, MMP-9 promoter reporter assay, RECK-specific siRNA, ChIP Cancer research Medium 19208844
2009 MT1-MMP and RECK exert opposing roles in hematopoietic progenitor cell (CD34+) motility. RECK expression is lower on circulating progenitors compared to bone marrow cells; G-CSF decreases RECK expression in a PI3K/Akt-dependent manner, elevating MT1-MMP activity. RECK neutralization with antibody promotes motility and egress of bone marrow CD34+ cells, while forced MT1-MMP inhibition impairs homing and mobilization. Anti-RECK neutralizing antibody, siRNA, anti-MT1-MMP antibody, in vivo mobilization in NOD/SCID chimeric mice, flow cytometry The Journal of clinical investigation High 19197139
2010 RECK is a target of miR-15b/16, miR-21, and miR-372/373. RECK mutants lacking miRNA target sites show augmented tumor/metastasis-suppressor activities. miR-372/373 are upregulated in response to hypoxia via HIF1α and TWIST1; miR-21 is upregulated by RAS/ERK signaling, demonstrating convergence of hypoxia and RAS pathways on RECK suppression through miRNAs. 3'UTR luciferase reporter, miRNA target site mutagenesis, hypoxia treatment, HIF1α/TWIST1 manipulation, tumor/metastasis suppression assays Oncogene High 20154725
2010 In Reck heterozygous mice (Reck+/-), tissue damage after transient cerebral ischemia is augmented, recovery of hippocampal long-term potentiation is compromised, MMP gelatinolytic activity is elevated, and laminin immunoreactivity is reduced, implicating Reck in protection of ECM integrity and neurological recovery after ischemia. Reck+/- mouse model, MMP zymography, immunohistochemistry, electrophysiological LTP recording Journal of neurochemistry Medium 20796170
2010 RECK is expressed in angiogenic blood vessels during uterine and embryonic vascular remodeling. shRNA-mediated Reck knockdown disrupts formation of vessels with compact, round lumens, and similar defects are seen in Reck-deficient and conditional knockout embryos, implicating Reck in non-sprouting (intussusceptive) angiogenesis. shRNA knockdown, Reck conditional knockout mouse, immunohistochemistry, morphological analysis BMC developmental biology Medium 20691046
2011 RECK expression induces cell-cycle arrest in colon carcinoma cells by downregulating SKP2 (a ubiquitin ligase component) and upregulating its substrate p27(KIP1). RECK-induced growth suppression is at least partially dependent on p27, and RECK and type I collagen share similar effects on the SKP2-p27 pathway. Acute RECK expression, cell cycle analysis, western blotting of SKP2 and p27, p27-dependent rescue experiments Oncogene Medium 22158033
2012 In zebrafish, Reck is expressed in neural crest cells and is required cell-autonomously for dorsal root ganglia (DRG) formation. Loss of reck function causes failure of sensory neuron precursors to migrate to the DRG position; four independent alleles of reck all lack DRG, and wild-type reck expression rescues the phenotype. Forward genetic screen, identification of four reck alleles, rescue experiment, cell-autonomous mosaic analysis Development (Cambridge, England) High 22296847
2013 STAT3 upregulates miR-92a, which post-transcriptionally suppresses RECK via its 3'UTR, leading to increased MMP activity and enhanced lung cancer cell invasion and migration. Anti-miR-92a restores RECK levels and reverses STAT3-induced invasiveness. 3'UTR luciferase reporter, STAT3 overexpression/inhibitor (S3I-201), pre-miR-92a and anti-miR-92a transfection, gelatin zymography, transwell assay British journal of cancer Medium 23820254
2015 Reck and Gpr124 function as integral components of a Wnt7a/Wnt7b-specific signaling complex required for brain angiogenesis (CNS vessel invasion) and DRG neurogenesis in zebrafish. Mosaic restoration of single wild-type tip cells in Wnt/β-catenin-deficient vessels is sufficient to initiate CNS vascular invasion, demonstrating that this pathway selectively controls tip cell function. Zebrafish genetic analysis, mosaic single-cell rescue, endothelial-specific expression, live imaging eLife High 26051822
2015 Forward genetic screen in zebrafish identified Reck as essential for intracerebral central artery (CtA) formation via canonical Wnt/β-catenin signaling in endothelial cells. reck mutants lack most intracerebral arteries; Reck promotes BBB molecular marker expression. In cultured endothelial cells, Reck also impacts the VEGF cascade. Forward genetic screen, zebrafish Reck loss-of-function, Wnt reporter assay in endothelial cells Development (Cambridge, England) High 26657775
2015 In glioblastoma cells, forced RECK expression inhibits invasion and migration through rearrangement of actin filaments, promoting stress fibers and mature focal adhesions with phospho-FAK, and reducing lamellipodia. RECK protein localizes predominantly at the leading edge of migrating cells, associated with membrane ruffles. RECK overexpression, transwell and wound assays, immunofluorescence, confocal microscopy for actin/FAK localization Journal of cellular biochemistry Medium 20127710
2015 RECK knockdown in human mesenchymal stem cells (hMSCs) promotes migration, reduces osteogenic differentiation, increases adipogenesis, and attenuates Wnt/β-catenin signaling (reduced β-catenin stability and reduced transcription of DKK1, AXIN2, RUNX2). RECK also suppresses TIMP-2 transcription but does not affect MMP-2, MMP-9, MT1-MMP, or TIMP-1 in these cells. siRNA knockdown, β-catenin reporter (BAR) luciferase assay, differentiation assays, scratch wound/chemotaxis assays Cellular and molecular life sciences : CMLS Medium 26459448
2017 Vascular endothelial cell-specific reduction of Reck impairs CNS angiogenesis, and postnatal EC-specific loss of Reck combined with loss of Norrin impairs blood-brain barrier maintenance. The N-terminal CC1 domain of Reck binds the LRR and Ig domains of Gpr124; targeted mutagenesis weakening this interaction (Reck CC1 mutations) reduces Reck/Gpr124 stimulation of Wnt7a signaling in cell culture and impairs CNS angiogenesis in vivo. Soluble Gpr124(LRR-Ig) binds cells expressing Frizzled + Wnt7a/7b + Reck, and soluble Reck(CC1-5) binds cells expressing Frizzled + Wnt7a/7b + Gpr124, demonstrating a tripartite cell-surface complex. Conditional EC-specific knockout, targeted domain mutagenesis, cell-binding assays with soluble probes, cell culture Wnt reporter assay Neuron High 28803732
2018 RECK directly binds WNT7A and WNT7B (but not WNT3A) with 1:1 stoichiometry as determined by chemical cross-linking and binding assays with purified recombinant soluble RECK. RECK binding stabilizes monomeric, hydrophilic-active WNT7A and prevents its aggregation into inactive hydrophilic aggregates. GPR124 is the predominant binding partner of RECK in rat brain blood vessels in situ, and the GPR124 ectodomain (not transmembrane/intracellular domains) mediates RECK/WNT7-induced canonical Wnt signaling. Direct binding assay with purified recombinant proteins, chemical cross-linking, stoichiometry determination, in situ binding (rat brain vessels), Wnt reporter assay with truncated GPR124 constructs Cell reports High 30304675
2019 Among amino acids distinguishing Wnt7a/7b from other Wnts, two clusters (one at the N-terminus, one in a protruding loop) are essential for Reck- and Gpr124-dependent signaling. Within Reck, substitutions P256A and W261A in the fourth CC domain (CC4) eliminate Wnt7a stimulation without changing protein abundance or surface localization. Mouse embryos carrying these CC4 mutations have severe forebrain angiogenesis defects. Site-directed mutagenesis of Reck CC4 domain and Wnt7a residues, Wnt reporter assay, surface localization analysis, mouse embryo phenotyping eLife High 31225798
2018 A shorter RECK isoform (generated by alternative splicing and alternative polyadenylation) promotes cell migration, opposing the canonical RECK isoform. The short RECK protein competes with MMP9 for binding to the Kazal motifs of canonical RECK, thereby liberating MMP9 from inactivating interaction with canonical RECK. Knockdown of the short isoform reduces fibroblast migration, whereas knockdown of canonical RECK increases migration. Isoform-specific siRNA knockdown, Matrigel invasion/migration assay, competitive binding assay between short RECK and MMP9 on canonical RECK Kazal motifs Molecular biology of the cell Medium 29874120
2021 GDE2 (glycerophosphodiester phosphodiesterase 2) stimulates ADAM10 α-secretase cleavage of APP by shedding and inactivating membrane-tethered RECK, a GPI-anchored inhibitor of ADAM10. In Alzheimer's disease, RECK is highly elevated on the membrane and GDE2 is abnormally sequestered inside neurons. Genetic ablation of GDE2 phenocopies elevated membrane RECK and causes reduced sAPPα, increased Aβ, and synaptic protein loss; RECK reduction restores APP processing balance. Genetic ablation (GDE2 KO mice), RECK reduction rescue experiment, biochemical fractionation, sAPPα/Aβ measurement, synaptic protein analysis Science translational medicine High 33731436
2022 The WNT7A/WNT7B/GPR124/RECK signaling module is required for mammalian limb development. Using combinations of conditional loss-of-function alleles for Wnt7a, Wnt7b, Gpr124, and Reck (including a Reck allele specifically defective in WNT7A/WNT7B signaling), these factors synergize in limb bone growth and patterning (Lmx1b expression, nail structure formation), establishing RECK as part of this signaling unit in a non-CNS context. Conditional knockout combinations, WNT7A/WNT7B-signaling-defective Reck knock-in allele, limb phenotyping Development (Cambridge, England) High 35552394
2013 FXR agonist substantially increases hepatic RECK mRNA and protein expression in vivo and in vitro. FXR directly binds an FXR response element within intron 1 of the mouse RECK gene to regulate RECK transcription. FXR agonist reverses the downregulation of RECK in livers from mice fed a methionine- and choline-deficient diet. FXR agonist treatment (in vivo and in vitro), ChIP/DNA binding assay for FXR response element, qRT-PCR and western blot Biochemical and biophysical research communications Medium 24291500
2017 RECK modulates ER stress by binding to and sequestering GRP78 (glucose-regulated protein 78), thereby releasing the transmembrane sensors (e.g., PERK), which activates eIF2α phosphorylation and enhances ER stress. RECK/GRP78 binding assay, PERK/eIF2α phosphorylation measurement (described in review context citing experimental results) International journal of molecular sciences Low 28134767
2023 Pancreatic Reck deletion in a PDAC mouse model dramatically augments spontaneous PDAC development with a mesenchymal phenotype, increased liver metastases, and EMT (with tumor cells giving rise to inflammatory CAF-like cells by lineage tracing). RECK re-expression in Reck-null PDAC cells markedly reduces liver metastases, shifts tumor phenotype to epithelial, downregulates MMP2 and MMP3, increases E-cadherin, and decreases EMT transcription factors. An MMP inhibitor recapitulates RECK effects on E-cadherin and EMT factors. Pancreatic conditional Reck knockout, lineage tracing, splenic transplantation model, RECK re-expression, MMP inhibitor treatment, western blotting The Journal of clinical investigation High 37712427
2010 RECK is upregulated in osteoarthritic (OA) cartilage chondrocytes. siRNA knockdown of RECK reduces chondrocyte spreading and focal adhesions and increases migration (in an MMP activity-dependent manner), while RECK overexpression inhibits migration and promotes proliferation via maintained phospho-FAK and phospho-ERK levels. siRNA knockdown, RECK overexpression, monolayer wound assay, MMP activity-dependent pharmacological rescue, immunohistochemistry, western blotting for FAK and ERK phosphorylation The American journal of pathology Medium 20395433
2015 RECK expression impedes DNA repair in breast cancer cells by inhibiting erbB signaling and attenuating downstream JAB1 and RAD51 expression, leading to activation of ATM/ATR pathways and γ-H2AX foci formation. Ectopic expression of JAB1 counteracts RECK-induced RAD51 reduction and drug sensitization; EGF or HER-2 overexpression reverses RECK inhibitory effects. RECK overexpression, γ-H2AX foci formation, ATM/ATR pathway activation assay, erbB signaling inhibition, JAB1 rescue expression, HER-2/EGF reversal American journal of cancer research Medium 26396917
2016 Adgra2 (Gpr124) and Reck traffic to the plasma membrane independently of each other: Adgra2 trafficking depends on precise LRR domain composition but occurs in a Reck-independent manner (CRISPR/Cas9 Adgra2-null cells), and Reck reaches the plasma membrane irrespective of Adgra2 expression, suggesting they meet at the plasma membrane after independent intracellular trafficking. CRISPR/Cas9 gene editing of Adgra2, subcellular localization assays, characterization of zebrafish ouchless allele (LRR domain deletion) Biology open Medium 27979830
2022 Mycoplasma pneumoniae infection decreases RECK expression in bronchial epithelial cells by inducing Sp1 phosphorylation. RECK overexpression significantly impairs M. pneumoniae-triggered MMP-9 enzymatic activity (without affecting MMP-9 protein level), establishing RECK as a post-translational regulator of MMP-9 activity in this context. RECK overexpression, MMP-9 activity assay, Sp1 phosphorylation analysis, specific pathway inhibitors and chromatin co-precipitation Virulence Medium 35892136

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2015 Tip cell-specific requirement for an atypical Gpr124- and Reck-dependent Wnt/β-catenin pathway during brain angiogenesis. eLife 219 26051822
2008 Expansion and countrywide dissemination of ST11, ST15 and ST147 ciprofloxacin-resistant CTX-M-15-type beta-lactamase-producing Klebsiella pneumoniae epidemic clones in Hungary in 2005--the new 'MRSAs'? The Journal of antimicrobial chemotherapy 189 18667450
2003 Histone deacetylase inhibitor up-regulates RECK to inhibit MMP-2 activation and cancer cell invasion. Cancer research 182 12810630
2017 Reck and Gpr124 Are Essential Receptor Cofactors for Wnt7a/Wnt7b-Specific Signaling in Mammalian CNS Angiogenesis and Blood-Brain Barrier Regulation. Neuron 161 28803732
2003 RECK: a novel suppressor of malignancy linking oncogenic signaling to extracellular matrix remodeling. Cancer metastasis reviews 119 12784995
2012 Oncogenic miRNA-182-5p targets Smad4 and RECK in human bladder cancer. PloS one 110 23226455
2017 Virulence genes in isolates of Klebsiella pneumoniae from the UK during 2016, including among carbapenemase gene-positive hypervirulent K1-ST23 and 'non-hypervirulent' types ST147, ST15 and ST383. Journal of medical microbiology 106 29205138
2004 Tissue inhibitors of metalloproteinase 2 inhibits endothelial cell migration through increased expression of RECK. Cancer research 98 15604273
2019 Empagliflozin reduces high glucose-induced oxidative stress and miR-21-dependent TRAF3IP2 induction and RECK suppression, and inhibits human renal proximal tubular epithelial cell migration and epithelial-to-mesenchymal transition. Cellular signalling 96 31862399
2018 A RECK-WNT7 Receptor-Ligand Interaction Enables Isoform-Specific Regulation of Wnt Bioavailability. Cell reports 94 30304675
2010 Hypoxia and RAS-signaling pathways converge on, and cooperatively downregulate, the RECK tumor-suppressor protein through microRNAs. Oncogene 92 20154725
2012 MicroRNA-21 expression is regulated by β-catenin/STAT3 pathway and promotes glioma cell invasion by direct targeting RECK. CNS neuroscience & therapeutics 91 22630347
2009 MT1-MMP and RECK are involved in human CD34+ progenitor cell retention, egress, and mobilization. The Journal of clinical investigation 85 19197139
2009 RECK negatively regulates matrix metalloproteinase-9 transcription. Cancer research 81 19208844
2013 STAT3 upregulates miR-92a to inhibit RECK expression and to promote invasiveness of lung cancer cells. British journal of cancer 76 23820254
2015 MicroRNA-135b, a HSF1 target, promotes tumor invasion and metastasis by regulating RECK and EVI5 in hepatocellular carcinoma. Oncotarget 67 25537516
2013 MicroRNA-221 promotes colorectal cancer cell invasion and metastasis by targeting RECK. FEBS letters 66 24269686
2014 MiR-374b-5p suppresses RECK expression and promotes gastric cancer cell invasion and metastasis. World journal of gastroenterology 59 25516656
2017 Nimbolide upregulates RECK by targeting miR-21 and HIF-1α in cell lines and in a hamster oral carcinogenesis model. Scientific reports 57 28515436
2008 RECK, a novel matrix metalloproteinase regulator. Histology and histopathology 57 18498076
2003 RECK is a target of Epstein-Barr virus latent membrane protein 1. Oncogene 57 14614450
2014 The RECK gene and biological malignancy--its significance in angiogenesis and inhibition of matrix metalloproteinases. Anticancer research 56 25075007
2014 MiR-96 downregulates RECK to promote growth and motility of non-small cell lung cancer cells. Molecular and cellular biochemistry 55 24469470
2005 RECK-mediated suppression of tumor cell invasion is regulated by glycosylation in human tumor cell lines. Cancer research 55 16103099
2013 miR-96 promotes tumor proliferation and invasion by targeting RECK in breast cancer. Oncology reports 54 24366472
2014 MiR-96 promotes proliferation and chemo- or radioresistance by down-regulating RECK in esophageal cancer. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 52 25465153
2013 Inhibition of miR-92b suppresses nonsmall cell lung cancer cells growth and motility by targeting RECK. Molecular and cellular biochemistry 51 24162673
2015 Controlling RECK miR21 Promotes Tumor Cell Invasion and Is Related to Biochemical Recurrence in Prostate Cancer. Journal of Cancer 50 25663948
2012 The metalloproteinase inhibitor Reck is essential for zebrafish DRG development. Development (Cambridge, England) 49 22296847
2007 RECK expression in osteosarcoma: correlation with matrix metalloproteinases activation and tumor invasiveness. Journal of orthopaedic research : official publication of the Orthopaedic Research Society 49 17262820
2002 Transcriptional control of the RECK metastasis/angiogenesis suppressor gene. Cancer detection and prevention 47 12507228
2019 Molecular determinants in Frizzled, Reck, and Wnt7a for ligand-specific signaling in neurovascular development. eLife 46 31225798
2015 MiR-21 overexpression improves osteoporosis by targeting RECK. Molecular and cellular biochemistry 46 25893734
2018 RECK inhibits cervical cancer cell migration and invasion by promoting p53 signaling pathway. Journal of cellular biochemistry 45 29064588
2018 miR-15b-5p facilitates the tumorigenicity by targeting RECK and predicts tumour recurrence in prostate cancer. Journal of cellular and molecular medicine 45 29363862
2015 Reck enables cerebrovascular development by promoting canonical Wnt signaling. Development (Cambridge, England) 45 26657775
2006 TIMP-2 upregulates RECK expression via dephosphorylation of paxillin tyrosine residues 31 and 118. Oncogene 44 16491114
2010 Involvement of the Reck tumor suppressor protein in maternal and embryonic vascular remodeling in mice. BMC developmental biology 42 20691046
2019 GAS5 Regulates RECK Expression and Inhibits Invasion Potential of HCC Cells by Sponging miR-135b. BioMed research international 40 30733959
2013 MicroRNA-15a promotes neuroblastoma migration by targeting reversion-inducing cysteine-rich protein with Kazal motifs (RECK) and regulating matrix metalloproteinase-9 expression. The FEBS journal 40 23176145
2023 Hypervirulent Klebsiella pneumoniae Causing Neonatal Bloodstream Infections: Emergence of NDM-1-Producing Hypervirulent ST11-K2 and ST15-K54 Strains Possessing pLVPK-Associated Markers. Microbiology spectrum 39 36752639
2014 Docosahexaenoic acid reverses angiotensin II-induced RECK suppression and cardiac fibroblast migration. Cellular signalling 39 24447911
2010 RECK-mediated inhibition of glioma migration and invasion. Journal of cellular biochemistry 38 20127710
2016 First Description of KPC-2-Producing Escherichia coli and ST15 OXA-48-Positive Klebsiella pneumoniae in Tunisia. Microbial drug resistance (Larchmont, N.Y.) 37 27754776
2021 GDE2-RECK controls ADAM10 α-secretase-mediated cleavage of amyloid precursor protein. Science translational medicine 35 33731436
2020 LncRNA SNHG8 accelerates proliferation and inhibits apoptosis in HPV-induced cervical cancer through recruiting EZH2 to epigenetically silence RECK expression. Journal of cellular biochemistry 35 31961005
2020 The role of miR-21/RECK in the inhibition of osteosarcoma by curcumin. Molecular and cellular probes 35 32081769
2014 Acetylsalicylic acid inhibits IL-18-induced cardiac fibroblast migration through the induction of RECK. Journal of cellular physiology 34 24265116
2014 Involvement of RECK in gambogic acid induced anti-invasive effect in A549 human lung carcinoma cells. Molecular carcinogenesis 34 24532189
2019 RECK suppresses interleukin-17/TRAF3IP2-mediated MMP-13 activation and human aortic smooth muscle cell migration and proliferation. Journal of cellular physiology 33 31074012
2019 Nosocomial spread of OXA-232-producing Klebsiella pneumoniae ST15 in a teaching hospital, Shanghai, China. BMC microbiology 33 31660869
2009 Expression of RECK and matrix metalloproteinase-2 in ameloblastoma. BMC cancer 32 19995435
2015 miR-221 and miR-222 Simultaneously Target RECK and Regulate Growth and Invasion of Gastric Cancer Cells. Medical science monitor : international medical journal of experimental and clinical research 31 26364844
2011 Involvement of the SKP2-p27(KIP1) pathway in suppression of cancer cell proliferation by RECK. Oncogene 31 22158033
2010 A novel screen using the Reck tumor suppressor gene promoter detects both conventional and metastasis-suppressing anticancer drugs. Oncotarget 31 21304177
2004 Expression and localisation of the new metalloproteinase inhibitor RECK (reversion inducing cysteine-rich protein with Kazal motifs) in inflamed synovial membranes of patients with rheumatoid arthritis. Annals of the rheumatic diseases 31 15485996
2006 Immunohistochemical detection of MT1-MMP, RECK, and EMMPRIN in ameloblastic tumors. Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology 30 16762015
2019 Elevation of long non-coding RNA GAS5 and knockdown of microRNA-21 up-regulate RECK expression to enhance esophageal squamous cell carcinoma cell radio-sensitivity after radiotherapy. Genomics 29 31866421
2016 MiR-200c promotes bladder cancer cell migration and invasion by directly targeting RECK. OncoTargets and therapy 29 27574450
2007 Expression of matrix metalloproteinases-2 and -9 and RECK during alveolar bone regeneration in rat. Journal of molecular histology 29 17987394
2018 Suppression of Non-Small Cell Lung Cancer Growth and Metastasis by a Novel Small Molecular Activator of RECK. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 26 29510387
2006 Downregulation of the RECK-tumor and metastasis suppressor gene in glioma invasiveness. Journal of cellular biochemistry 26 16791855
2020 Clinical and Molecular Description of a High-Copy IncQ1 KPC-2 Plasmid Harbored by the International ST15 Klebsiella pneumoniae Clone. mSphere 25 33028683
2020 LINC01419 facilitates hepatocellular carcinoma growth and metastasis through targeting EZH2-regulated RECK. Aging 24 32522890
2017 HDAC Inhibitors and RECK Modulate Endoplasmic Reticulum Stress in Tumor Cells. International journal of molecular sciences 24 28134767
2021 Salvianolic acid B targets mortalin and inhibits the migration and invasion of hepatocellular carcinoma via the RECK/STAT3 pathway. Cancer cell international 23 34876128
2017 AKT Axis, miR-21, and RECK Play Pivotal Roles in Dihydroartemisinin Killing Malignant Glioma Cells. International journal of molecular sciences 23 28208619
2021 Detection of extensively drug-resistant and hypervirulent Klebsiella pneumoniae ST15, ST147, ST377 and ST442 in Iran. Acta microbiologica et immunologica Hungarica 22 34546968
2019 Minocycline inhibits PDGF-BB-induced human aortic smooth muscle cell proliferation and migration by reversing miR-221- and -222-mediated RECK suppression. Cellular signalling 22 30716386
2018 RECK isoforms have opposing effects on cell migration. Molecular biology of the cell 22 29874120
2016 Promotion of tumour proliferation, migration and invasion by miR-92b in targeting RECK in osteosarcoma. Clinical science (London, England : 1979) 22 26993249
2023 FXR agonists INT-787 and OCA increase RECK and inhibit liver steatosis and inflammation in diet-induced ob/ob mouse model of NASH. Liver international : official journal of the International Association for the Study of the Liver 21 37904642
2021 Reck-Notch1 Signaling Mediates miR-221/222 Regulation of Lung Cancer Stem Cells in NSCLC. Frontiers in cell and developmental biology 21 33959615
2016 A Hypothesis for the Role of RECK in Angiogenesis. Current vascular pharmacology 21 26463982
2015 RECK (reversion-inducing cysteine-rich protein with Kazal motifs) regulates migration, differentiation and Wnt/β-catenin signaling in human mesenchymal stem cells. Cellular and molecular life sciences : CMLS 21 26459448
2010 Expression of matrix metalloproteinase regulator, RECK, and its clinical significance in osteosarcoma. Journal of orthopaedic research : official publication of the Orthopaedic Research Society 21 20973064
2019 Curcumin suppresses wilms' tumor metastasis by inhibiting RECK methylation. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 20 30841433
2012 The potential of RECK inducers as antitumor agents for glioma. Anticancer research 20 22753763
2023 Pancreatic RECK inactivation promotes cancer formation, epithelial-mesenchymal transition, and metastasis. The Journal of clinical investigation 19 37712427
2019 Down-regulated microRNA-30b-3p inhibits proliferation, invasion and migration of glioma cells via inactivation of the AKT signaling pathway by up-regulating RECK. Bioscience reports 19 31270250
2018 MicroRNA-96 Promotes Tumor Invasion in Colorectal Cancer via RECK. Anticancer research 19 29599320
2011 MT1-MMP and RECK: opposite and essential roles in hematopoietic stem and progenitor cell retention and migration. Journal of molecular medicine (Berlin, Germany) 19 21842347
2020 Exosomal miR-182 regulates the effect of RECK on gallbladder cancer. World journal of gastroenterology 18 32206004
2016 Molecular insights into Adgra2/Gpr124 and Reck intracellular trafficking. Biology open 18 27979830
2011 Expression of RECK in endothelial cells of glioma: comparison with CD34 and VEGF expressions. Journal of neuro-oncology 18 22183444
2010 The Reck tumor suppressor protein alleviates tissue damage and promotes functional recovery after transient cerebral ischemia in mice. Journal of neurochemistry 18 20796170
2021 Vegetable-Derived Carbapenemase-Producing High-Risk Klebsiella pneumoniae ST15 and Acinetobacter baumannii ST2 Clones in Japan: Coexistence of blaNDM-1, blaOXA-66, blaOXA-72, and an AbaR4-Like Resistance Island in the Same Sample. Applied and environmental microbiology 17 33674428
2021 Dihydroartemisinin regulates apoptosis, migration, and invasion of ovarian cancer cells via mediating RECK. Journal of pharmacological sciences 16 33941323
2019 MiR-92a promotes the invasion and migration of colorectal cancer by targeting RECK. International journal of clinical and experimental pathology 16 31933974
2010 RECK is up-regulated and involved in chondrocyte cloning in human osteoarthritic cartilage. The American journal of pathology 16 20395433
2005 Expression of RECK gene and MMP-9 in hilar cholangiocarcinoma and its clinical significance. Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban 16 16463672
2023 The BAP31/miR-181a-5p/RECK axis promotes angiogenesis in colorectal cancer via fibroblast activation. Frontiers in oncology 15 36895489
2022 The WNT7A/WNT7B/GPR124/RECK signaling module plays an essential role in mammalian limb development. Development (Cambridge, England) 15 35552394
2022 Mycoplasma pneumoniae downregulates RECK to promote matrix metalloproteinase-9 secretion by bronchial epithelial cells. Virulence 15 35892136
2022 Identification of KPC-112 from an ST15 Klebsiella pneumoniae Strain Conferring Resistance to Ceftazidime-Avibactam. mSphere 15 36374086
2017 Preeclampsia associates with RECK-dependent decrease in human trophoblasts migration and invasion. Placenta 15 29108633
2015 RECK impedes DNA repair by inhibiting the erbB/JAB1/Rad51 signaling axis and enhances chemosensitivity of breast cancer cells. American journal of cancer research 15 26396917
2015 Isolation and characterization of novel RECK tumor suppressor gene splice variants. Oncotarget 15 26431549
2013 Activation of farnesoid X receptor induces RECK expression in mouse liver. Biochemical and biophysical research communications 15 24291500
2024 MiR-21 Regulates Growth and Migration of Cervical Cancer Cells by RECK Signaling Pathway. International journal of molecular sciences 14 38612895

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