Affinage

IGFBP5

Insulin-like growth factor-binding protein 5 · UniProt P24593

Length
272 aa
Mass
30.6 kDa
Annotated
2026-06-10
100 papers in source corpus 36 papers cited in narrative 34 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

IGFBP5 is a secreted regulator of the insulin-like growth factor (IGF) axis that controls cell survival, proliferation, differentiation, senescence and fibrosis in a context-dependent manner (PMID:12223411, PMID:26854565). Its N-terminal domain adopts a globular fold with a single high-affinity IGF-binding site that binds IGF-I/II and competes with the IGF-I receptor, blocking receptor autophosphorylation and downstream Akt signaling (PMID:9822601, PMID:11447105); in vivo this sequestering activity is potent enough to induce mammary apoptosis (loss of Bcl-2/Bcl-xL, increased caspase-3) and to rescue the lethal excess-IGF-II phenotype of Igf2r-null mice, effects that require an intact IGF-binding site (PMID:12223411, PMID:15010534, PMID:19332648). IGFBP5 also exerts IGF-independent functions, dissected with IGF-binding-deficient mutants: it suppresses the intrinsic caspase-9 apoptotic pathway to promote survival and signals through Ras–p38/Erk and the intracellular partner RASSF1C (PMID:15075235, PMID:11923300, PMID:16007340). Extracellularly, its C-terminal heparin-binding domain mediates interactions with matrix proteins vitronectin and with α2β1 integrins, modulating adhesion, migration and survival, with N- and C-terminal domains carrying separable growth-suppressive versus anti-invasive activities (PMID:11751588, PMID:22328518, PMID:23665505). Subcellular partitioning further tunes outcome: nuclear IGFBP5 is growth-suppressive while cytoplasmic redirection is growth-promoting (PMID:19341485). IGFBP5 sits at the output of multiple regulatory circuits — it is a HIF1α/mTORC1 target that acts as a feedback inhibitor of IGF-1 signaling (PMID:26854565), a STAT3 effector driving IL-6-induced senescence via ROS (PMID:22374671), and a gene whose expression is set by an EZH2/KDM6B–H3K27me3 epigenetic switch in endothelium, stem cells and drug-resistant tumors (PMID:29896299, PMID:25827480, PMID:29925528). In disease contexts it promotes pulmonary and diabetic renal fibrosis through ECM/CTGF/LOX induction and EGR1–PFKFB3-driven endothelial glycolysis and inflammasome activation (PMID:30374330, PMID:35418167, PMID:40423799), and acts as a ligand for ROR1 to drive ROR1/HER2 heterodimerization and CREB-mediated invasion in glioblastoma (PMID:36949068).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 1998 High

    Established the structural and biochemical basis for how IGFBP5 captures IGF and antagonizes the IGF-I receptor, defining its core molecular activity.

    Evidence NMR structure of the N-terminal mini-IGFBP-5 domain with IGF-I receptor binding and autophosphorylation assays

    PMID:9822601

    Open questions at the time
    • Did not resolve the C-terminal domain or full-length protein structure
    • Functional consequences of IGF sequestration in cells/tissues not addressed
  2. 2001 High

    Atomic-resolution co-crystal structure clarified the interlaced hydrophobic interface and showed how IGFBP5 binding occludes the IGF-I receptor-binding surface.

    Evidence 2.1 Å X-ray co-crystal structure of IGF-I:mini-IGFBP-5

    PMID:11447105

    Open questions at the time
    • Only the isolated N-terminal complex was crystallized
    • Does not address IGF-independent activities
  3. 2002 High

    Demonstrated that IGFBP5 induces cell death principally by sequestering IGF-I and blocking IGF-I receptor/Akt signaling, validating the sequestration model in vivo.

    Evidence Transgenic mammary overexpression with R3-IGF-I and growth hormone rescue, apoptosis and phosphorylation readouts

    PMID:12223411

    Open questions at the time
    • Did not separate IGF-dependent from IGF-independent contributions in this model
    • Mechanism of caspase-3/plasmin induction not fully resolved
  4. 2002 Medium

    Revealed IGF-independent and matrix-contextual activities: IGFBP5 can stimulate growth via Ras-p38/Erk, bind vitronectin to enhance IGF-I responses, and switch between pro- and anti-survival depending on fibronectin.

    Evidence Kinase inhibitors and dominant-negative Ras in smooth muscle cells; vitronectin mutagenesis and adhesion assays; ceramide apoptosis assays in breast cancer cells

    PMID:11751588 PMID:11835403 PMID:11923300 PMID:12376561

    Open questions at the time
    • Receptor/transducer for IGF-independent Ras signaling not identified here
    • Matrix-context dependence mechanistically incomplete (pharmacological inhibitors only)
  5. 2004 High

    IGF-binding-deficient mutants and ubiquitous transgenics formally partitioned IGFBP5 into IGF-dependent differentiation/growth control and IGF-independent caspase-9 survival functions.

    Evidence Myc-tagged WT vs non-IGF-binding mutant in C2 myoblasts with caspase assays; transgenic overexpression and Igf2r-null genetic rescue

    PMID:15010534 PMID:15075235 PMID:19332648

    Open questions at the time
    • Molecular target of the IGF-independent survival arm not defined
    • Circulating free IGF-I changes were undetectable despite phenotypes, leaving the in vivo mechanism partly unresolved
  6. 2005 Medium

    Identified RASSF1C as an intracellular IGFBP5 partner mediating IGF-independent ERK signaling, providing a candidate transducer for non-sequestration functions.

    Evidence Yeast two-hybrid, Co-IP, and siRNA with ERK phosphorylation and proliferation in osteoblasts

    PMID:16007340

    Open questions at the time
    • Single lab; no reciprocal validation or structural mapping of the interaction
    • How a secreted protein engages an intracellular partner not mechanistically explained
  7. 2008 High

    Showed IGFBP5 can also potentiate IGF action—binding IGF-II to drive a PI3K-Akt autoregulatory loop promoting myogenic differentiation.

    Evidence siRNA, constitutively active Akt rescue, IGF analogue competition and IGF-binding-deficient mutant in myoblasts

    PMID:18762576

    Open questions at the time
    • Context determinants distinguishing potentiation from inhibition not defined
    • Did not reconcile with caspase-9 IGF-independent survival arm
  8. 2009 Medium

    Demonstrated that subcellular localization is a functional switch—nuclear IGFBP5 suppresses growth/motility whereas cytoplasmic IGFBP5 promotes them.

    Evidence NLS mutagenesis with fluorescent fusion localization and growth/motility assays in breast cancer cells

    PMID:19341485

    Open questions at the time
    • Nuclear molecular targets and import mechanism not identified
    • Single cell line and single lab
  9. 2012 High

    Mapped IGFBP5's matrix-receptor activity to direct α2β1 integrin binding via the C-terminal heparin-binding domain, activating Cdc42/ILK/Akt to promote adhesion and survival independently of IGF.

    Evidence Domain truncation and IGF-binding-deficient mutants, integrin blocking antibodies, and signaling readouts in breast cancer cells

    PMID:22328518

    Open questions at the time
    • Migration mechanism distinct from adhesion remains undefined
    • Stoichiometry/affinity of the integrin interaction not quantified
  10. 2012 High

    Placed IGFBP5 within paracrine and feedback circuits driving senescence and bone coupling: a STAT3 effector mediating IL-6-induced ROS/senescence and a c-Src/STAT3/IL-6 amplifier and osteoblast-osteoclast coupling factor.

    Evidence STAT3 and IGFBP5 knockdown with ROS/senescence readouts in fibroblasts; pathway epistasis and osteoclastogenesis assays in osteoblasts

    PMID:22252554 PMID:22374671

    Open questions at the time
    • How secreted IGFBP5 triggers intracellular ROS not mechanistically resolved
    • Receptor mediating the senescence-inducing activity not identified
  11. 2012 Medium

    Positioned IGFBP5 as a required downstream effector of tumor regulatory pathways—repressed by Wnt/β-catenin in mammary tumors such that its induction drives regression.

    Evidence MMTV-Wnt1 tumor model with Fzd8CRD treatment and IGFBP5 knockdown rescue

    PMID:22307840

    Open questions at the time
    • Mechanism of Wnt-mediated IGFBP5 repression not defined
    • Single in vivo model
  12. 2013 Medium

    Defined separable domain functions in cancer—N-terminal domain inhibits proliferation/apoptosis while C-terminal domain suppresses migration, invasion and metastasis.

    Evidence Domain truncation mutants with in vitro assays and xenograft/pulmonary metastasis models in osteosarcoma

    PMID:23665505

    Open questions at the time
    • Molecular partners for each domain activity not fully identified
    • Single tumor type and lab
  13. 2015 Medium

    Reinforced a tumor-suppressive signaling output—IGFBP5 reduces IGF1R/ERK/p38 phosphorylation and HIF1α/VEGF/MMP9 to suppress EMT in melanoma.

    Evidence Reciprocal overexpression and knockdown with signaling and EMT readouts plus xenograft/metastasis models

    PMID:26010068

    Open questions at the time
    • IGF-dependent vs independent contributions not separated
    • Single lab
  14. 2016 High

    Established IGFBP5 as a secreted mTORC1-HIF1α transcriptional target functioning as a feedback inhibitor of IGF-1 signaling, integrating it into nutrient/growth sensing.

    Evidence Quantitative secretome proteomics of rapamycin-sensitive TSC2−/− MEFs with HIF1α ChIP/reporter and IGF-1 signaling assays

    PMID:26854565

    Open questions at the time
    • Quantitative contribution of secreted IGFBP5 versus intracellular feedback branches not delineated
    • Tissue contexts where this feedback operates not mapped
  15. 2016 High

    Identified an EZH2/H3K27me3 epigenetic switch (flow→miR-101→EZH2) as a key determinant of endothelial IGFBP5 expression linked to anti-inflammatory programming.

    Evidence EZH2 silencing/inhibition, H3K27me3 ChIP, adenoviral IGFBP5 overexpression and monocyte adhesion/in vivo aorta staining

    PMID:29896299

    Open questions at the time
    • Downstream effectors of IGFBP5's anti-inflammatory action not fully defined
    • Receptor mediating endothelial response unidentified
  16. 2018 High

    Showed KDM6B antagonizes EZH2 at the IGFBP5 promoter, and an H3K27me3-to-H3K27Ac switch driving IGFBP5 upregulation underlies PI3K-inhibitor resistance in breast cancer.

    Evidence KDM6B gain/loss, H3K27me3/H3K27Ac ChIP and IGFBP5 siRNA in PI3K inhibitor-resistant cells

    PMID:25827480 PMID:29925528

    Open questions at the time
    • How IGFBP5 mediates drug-resistant survival signaling not fully mechanistic
    • Generalizability across resistance models untested here
  17. 2018 Medium

    Demonstrated a pro-fibrotic role—IGFBP5 induces collagen, fibronectin, CTGF and LOX in lung fibroblasts via a self-amplifying feedback loop.

    Evidence Recombinant and adenoviral IGFBP5, siRNA, and human lung organ culture with ECM gene readouts

    PMID:30374330

    Open questions at the time
    • Receptor/signaling pathway driving ECM induction not identified
    • Single lab
  18. 2019 Medium

    Identified transcriptional and epigenetic regulators of IGFBP5 in cancer—PKNOX2 directly activates IGFBP5 in a p53 tumor-suppressor pathway, while Mybbp1a-DNMT1 silences IGFBP5 to activate IGF1/AKT.

    Evidence ChIP-PCR, bisulfite sequencing, Co-IP and epistasis rescue with xenografts in gastric and hepatocellular cancer

    PMID:30745575 PMID:31109829

    Open questions at the time
    • Direct mechanism by which secreted IGFBP5 elevates p53 not defined
    • Single lab per pathway
  19. 2022 Medium

    Connected IGFBP5 to metabolic reprogramming in diabetic kidney disease via an EGR1-PFKFB3 axis that enhances endothelial glycolysis and inflammation.

    Evidence IGFBP5 ablation in diabetic mice with EGR1/PFKFB3 expression, ECAR/lactate measurement and PFKFB3 mutant rescue

    PMID:35418167

    Open questions at the time
    • How IGFBP5 activates EGR1 (receptor/signal) not defined
    • Single lab
  20. 2023 High

    Discovered a receptor-ligand role: IGFBP5 binds ROR1 to promote ROR1/HER2 heterodimerization and CREB-mediated invasion in glioblastoma, defining a new signaling axis.

    Evidence Co-IP/binding and heterodimer pulldown, CREB reporter, ETV5/FBXW9 readouts and patient-derived xenograft invasion with CRISPR editing

    PMID:36949068

    Open questions at the time
    • Binding interface/affinity of IGFBP5-ROR1 not structurally mapped
    • Whether this receptor activity operates outside glioblastoma unknown
  21. 2025 Medium

    Extended the diabetic-nephropathy mechanism—IGFBP5-driven glycolysis raises H3K18 lactylation to activate the NLRP3 inflammasome, promoting EndoMT and renal fibrosis.

    Evidence IGFBP5 siRNA in glomerular endothelial cells and DN mice with glycolysis, H3K18 lactylation, NLRP3 and EndoMT readouts

    PMID:40423799

    Open questions at the time
    • Upstream receptor coupling IGFBP5 to glycolysis not identified
    • Single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how secreted IGFBP5 transduces its diverse IGF-independent signals—the cell-surface receptor(s) beyond ROR1 and integrins, the route by which it engages intracellular/nuclear partners, and what dictates its context-dependent pro- versus anti-tumor and pro- versus anti-survival outcomes.
  • No unified receptor model for IGF-independent signaling
  • Determinants of nuclear vs cytoplasmic partitioning unknown
  • No structure of full-length IGFBP5 or its C-terminal domain

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 4 GO:0140313 molecular sequestering activity 3 GO:0008092 cytoskeletal protein binding 2
Localization
GO:0005576 extracellular region 3 GO:0031012 extracellular matrix 2 GO:0005634 nucleus 1
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-4839726 Chromatin organization 4 R-HSA-1266738 Developmental Biology 3 R-HSA-8953897 Cellular responses to stimuli 3 R-HSA-5357801 Programmed Cell Death 2
Partners
ERBB2IGF1IGF2ITGA2ITGB1RASSF1CROR1VTN

Evidence

Reading pass · 34 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 NMR solution structure of the N-terminal IGF-binding domain of IGFBP-5 (mini-IGFBP-5, residues 40-92) revealed a globular fold with a three-stranded anti-parallel beta-sheet stabilized by two disulfide bridges. The single high-affinity IGF-binding site involves conserved Leu and Val residues in a hydrophobic surface patch. IGFBP-5 inhibits IGF binding to the IGF-I receptor and blocks receptor autophosphorylation; smaller N-terminal fragments are less potent inhibitors. NMR structure determination; IGF-I receptor binding assay; receptor autophosphorylation assay; in vitro IGF-binding with deletion fragments The EMBO journal High 9822601
2001 2.1 Å crystal structure of IGF-I bound to the N-terminal domain of IGFBP-5 (mini-IGFBP-5) revealed that the principal interactions are interlaced hydrophobic side chains from both proteins, surrounded by polar interactions. A solvent-exposed hydrophobic patch on the opposite pole of IGF-I marks the IGF-I receptor binding site, clarifying the mechanism of IGF-I receptor competition. X-ray crystallography (2.1 Å); co-crystal structure of IGF-I:mini-IGFBP-5 complex The EMBO journal High 11447105
2002 Vitronectin binds IGFBP-5 with high affinity in solution; this interaction is mediated by basic residues R134, R136, K138, K139, R201, and K202 in two regions (aa 131-141 and aa 201-218) and is inhibitable by glycosaminoglycans. When IGFBP-5 is localized to a vitronectin-enriched matrix, IGF-I-stimulated smooth muscle cell DNA synthesis and migration are enhanced; IGFBP-5 mutants unable to bind vitronectin do not confer this enhancement. Solution binding assays; synthetic peptide competitive binding; site-directed mutagenesis; smooth muscle cell DNA synthesis and migration assays on vitronectin matrix Endocrinology High 11751588
2002 IGFBP-5 overexpression in transgenic mouse mammary glands caused premature apoptosis, reduced Bcl-2 and Bcl-xL, increased caspase-3 and plasmin, and inhibited IGF-I receptor and Akt phosphorylation. Rescue with R3-IGF-1 (which binds weakly to IGFBP-5) normalized mammary development, while growth hormone treatment (raising endogenous IGF-1) did not, demonstrating that IGFBP-5 induces cell death primarily by sequestering IGF-I and blocking IGF-I receptor/Akt signaling. Transgenic mouse mammary-specific overexpression; IGF receptor and Akt phosphorylation assays; BrdU labeling; DNA laddering; caspase-3 measurement; R3-IGF-I rescue experiments Development High 12223411
2002 IGFBP-5 stimulates growth and IGF-I secretion in human intestinal smooth muscle cells independently of IGF-I and the IGF-I receptor tyrosine kinase, acting through Ras-dependent activation of both p38 MAP kinase and Erk1/2 pathways. Inhibition of either pathway partially reduced the effect; combined inhibition or dominant-negative Ras abolished it. In vitro [3H]thymidine incorporation; pharmacological kinase inhibitors (SB203580, U0126); dominant-negative Ras(S17N) expression; IGF-I secretion assay The Journal of biological chemistry High 11923300
2002 IGFBP-5 has IGF-independent effects on Hs578T breast cancer cell survival: it protects against ceramide-induced apoptosis in the absence of fibronectin but loses this protective effect (and promotes death) when fibronectin is present. The survival and adhesion effects of IGFBP-5 require sphingosine kinase and protein kinase C activity, as inhibition of either reverses IGFBP-5-mediated protection. Cell viability assays; apoptosis flow cytometry; cell adhesion assay; pharmacological inhibitors of sphingosine kinase (DMS) and PKC (chelerythrine) Journal of cell science; Journal of cellular biochemistry Medium 11835403 12376561
2004 In C2 myoblasts, wild-type IGFBP-5 inhibited myogenesis (IGF-dependent effect) while both wild-type and IGF-binding-deficient mutant IGFBP-5 equally increased cell survival by inhibiting the intrinsic (caspase-9) apoptotic pathway in an IGF-independent manner. This partitions IGFBP-5 action into IGF-dependent differentiation inhibition and IGF-independent cell survival. Transfection of myc-tagged wild-type vs. non-IGF-binding mutant IGFBP-5 in C2 myoblasts; caspase-3 and caspase-9 activity assays; annexin V binding; MHC immunocytochemistry; co-transfection with antisense Igf2 Journal of cell science High 15075235
2004 Ubiquitous overexpression of wild-type IGFBP-5 in transgenic mice inhibited growth, reduced fertility, and impaired muscle development; circulating free IGF-I was not detectably reduced despite elevated IGFBP-5. Overexpression of wild-type but not IGF-binding-deficient Igfbp5 rescued the lethal excess-IGF-II phenotype of type-2 IGF receptor-null mice, demonstrating potent in vivo IGF-sequestering activity. Transgenic mouse overexpression (wild-type and N-terminal IGF-binding mutant); genetic rescue cross with Igf2r-null mice; serum IGF-I and IGFBP-5 measurements; growth and fertility phenotyping PNAS; FASEB journal High 15010534 19332648
2005 RASSF1C was identified as an intracellular binding partner of IGFBP-5 by yeast two-hybrid screening and confirmed by co-immunoprecipitation. Silencing RASSF1C with siRNA abolished IGFBP-5-induced ERK1/2 phosphorylation and reduced osteoblast cell number, indicating RASSF1C mediates IGF-independent ERK signaling downstream of IGFBP-5. Yeast two-hybrid screen; co-immunoprecipitation; siRNA knockdown; ERK1/2 phosphorylation immunoblot; AlamarBlue cell proliferation assay Journal of bone and mineral research Medium 16007340
2005 IGFBP-5 overexpression in differentiating chondrocytes potentiated IGF-I-enhanced chondrocyte differentiation specifically by increasing Akt phosphorylation (PI3K pathway activation) in the presence of IGF-I, without IGF-independent effects on differentiation. IGFBP-5 overexpression in RCJ chondrogenic cells; Akt phosphorylation immunoblot; differentiation assays American journal of physiology. Endocrinology and metabolism Medium 16204335
2008 IGFBP-5 promotes myogenic differentiation by binding to IGF-II and activating the IGF-II auto-regulation loop via PI3K-Akt signaling. Knockdown of IGFBP-5 impaired myogenesis and suppressed IGF-II expression; rescue required either constitutively active Akt or IGF-II itself, but not an IGF analogue that cannot bind IGFBPs. An IGF-binding-deficient IGFBP-5 mutant could not rescue defects when combined with low IGF-II concentrations. siRNA knockdown; constitutively active Akt rescue; IGF analogue competition; IGF-binding-deficient IGFBP-5 mutant rescue; PI3K inhibitor; real-time PCR for IGF-II expression The Journal of cell biology High 18762576
2009 Subcellular localization of IGFBP5 determines its function: nuclear-localizing wild-type IGFBP5 suppressed proliferation and motility in MDA-MB-435 breast cancer cells, whereas a nuclear localization sequence (NLS) mutant that redirected IGFBP5 to the cytoplasm increased proliferation and migration. Site-directed mutagenesis of NLS; stable transfection of wild-type vs. NLS-mutant IGFBP5; fluorescence microscopy (pDsRed fusion); cell growth rate and motility assays BMC cancer Medium 19341485
2009 IGFBP-5 induces migration of lung fibroblasts and peripheral blood mononuclear cells (preferentially monocytes/macrophages, NK cells, and CD4+ T cells) via MAPK (MEK1/2) activation independently of IGF-I. IGFBP-5 also induced transformation of monocytes into mesenchymal cells expressing alpha-smooth muscle actin and fibronectin in vitro and in vivo. Migration assays; MEK1/2 inhibitor (U0126); flow cytometry of cell subsets; immunostaining for mesenchymal markers in vitro and in vivo American journal of respiratory cell and molecular biology Medium 19131643
2012 IGFBP5 acts downstream of a c-Src → STAT3 → IL-6 loop in immature osteoblasts: c-Src stimulates STAT3, which induces IGFBP5 expression; IGFBP5 in turn reactivates c-Src (amplifying the loop) only in immature osteoblasts. In mature osteoblasts, IGFBP5 is induced by Runx2 but fails to reactivate c-Src because c-Src is downregulated. IGFBP5 produced by osteoblasts also stimulates osteoclastogenesis and bone resorption, functioning as an osteoblast-osteoclast coupling factor. In vitro osteoblast differentiation; siRNA/overexpression; STAT3 reporter; c-Src kinase activity assay; osteoclastogenesis assays; in vivo validation Nature communications High 22252554
2012 IL-6/soluble IL-6R induces premature senescence in human fibroblasts via a STAT3-IGFBP5 axis: STAT3 is required for early ROS increase and subsequent senescence; IGFBP5 is a major STAT3-downstream mediator secreted from early stimulation through senescence and is responsible for the ROS increase and senescence-inducing activity in conditioned media. STAT3 siRNA; IGFBP5 knockdown; ROS measurement; DNA damage response markers; p53 accumulation; conditioned media functional assays; senescence-associated beta-galactosidase Cell cycle High 22374671
2012 IGFBP5 increases adhesion of MCF-7 breast cancer epithelial cells to mesenchymal but not epithelial extracellular matrix via direct interaction with α2β1 integrins, requiring the C-terminal heparin-binding domain. This adhesion effect is IGF-independent, activates Cdc42, integrin-linked kinase (ILK), and Akt, prolongs cell survival, decreases p38 MAPK phosphorylation, and inhibits cell migration (the migration effect requires a different mechanism than adhesion). IGFBP5 mutants (C-terminal truncations; IGF-binding-deficient); integrin blocking antibodies; Cdc42/ILK/Akt/p38 phosphorylation assays; cell adhesion and migration assays; nutrient deprivation survival assay Journal of cell science High 22328518
2012 Wnt/β-catenin signaling represses IGFBP5 expression in mammary tumors; inhibition of Wnt signaling with Fzd8CRD acutely induces IGFBP5, which mediates tumor regression. IGFBP5 knockdown prevented Fzd8CRD-induced regression, placing IGFBP5 downstream of Wnt/β-catenin as a required effector of tumor involution. MMTV-Wnt1 transgenic tumor model; Fzd8CRD treatment; IGFBP5 knockdown rescue experiment; gene expression analysis Cancer research Medium 22307840
2013 In osteosarcoma, the N-terminal domain of IGFBP5 inhibits cell proliferation and induces apoptosis while the C-terminal domain inhibits cell migration and invasion. The C-terminal domain decreases both tumor growth and pulmonary metastasis in vivo, whereas the N-terminal domain reduces tumor growth without affecting metastasis, demonstrating domain-specific activities. Domain truncation/deletion mutants expressed in osteosarcoma cells; in vitro proliferation, apoptosis, migration, and invasion assays; xenograft tumor growth; pulmonary metastasis model Cancer letters Medium 23665505
2015 IGFBP5 exerts its tumor-suppressive activity in melanoma by reducing phosphorylation of IGF1R, ERK1/2, and p38-MAPK, decreasing expression of HIF1α and its targets VEGF and MMP9, and suppressing EMT. These effects were confirmed by both overexpression (A375 cells) and knockdown (A2058 cells) experiments. IGFBP5 overexpression and siRNA knockdown; IGF1R/ERK1/2/p38 phosphorylation immunoblot; HIF1α/VEGF/MMP9 expression; EMT markers; xenograft and in vivo metastasis models Oncotarget Medium 26010068
2015 KDM6B histone demethylase promotes IGFBP5 expression by removing repressive H3K27me3 marks from the IGFBP5 promoter; depletion of KDM6B increases H3K27me3 at the IGFBP5 promoter and downregulates IGFBP5. IGFBP5 in turn enhances osteogenic differentiation of MSCs and promotes anti-inflammatory effects via suppression of NF-κB signaling. KDM6B knockdown; ChIP for H3K27me3 at IGFBP5 promoter; IGFBP5 gain/loss-of-function; ALP activity; NF-κB reporter; swine periodontitis model Stem cells High 25827480
2016 Secreted IGFBP5 is a direct transcriptional target of HIF1α (itself an mTORC1 target) and functions as a rapamycin-sensitive, mTORC1-dependent feedback inhibitor of IGF-1 signaling. Once secreted, IGFBP5 cooperates with intracellular feedback branches to block IGF-1 signaling; identified by quantitative proteomic profiling of the rapamycin-sensitive secretome in TSC2−/− MEFs. Large-scale quantitative secretome proteomics; rapamycin treatment; HIF1α ChIP/reporter assays; TSC2−/− MEFs; IGF-1 signaling readouts; proliferation assays with IGF-1R inhibitors Nature cell biology High 26854565
2016 IGFBP5 enhances osteogenic differentiation of periodontal ligament stem cells and Wharton's jelly umbilical cord stem cells via activation of JNK and MEK/Erk signaling pathways; inhibition of either pathway by SP600125 (JNK) or PD98059 (MEK/Erk) blocked IGFBP5-enhanced ALP activity and mineralization. IGFBP5 overexpression/knockdown; recombinant IGFBP5 protein treatment; JNK and MEK/Erk inhibitors; p-JNK/p-MEK/p-Erk1/2 immunoblot; ALP activity; Alizarin Red staining Cell proliferation Medium 27484838
2018 Laminar (atheroprotective) blood flow reduces EZH2 expression via mechanosensitive miR-101, decreasing H3K27me3 at the IGFBP5 locus and upregulating IGFBP5 expression. Adenoviral IGFBP5 overexpression recapitulates the anti-inflammatory effects of H3K27me3 inhibition, linking the flow→miR-101→EZH2→H3K27me3→IGFBP5 axis to endothelial anti-inflammatory gene programming. EZH2 siRNA/inhibitor (GSK126); adenoviral IGFBP5 overexpression; H3K27me3 ChIP; RNA-seq; monocyte adhesion assay; en face staining of mouse aorta Theranostics High 29896299
2018 KDM6B antagonizes EZH2-mediated H3K27me3 repression at the IGFBP5 promoter to sustain IGFBP5 expression. Acquired PI3K inhibitor (GDC-0941) resistance in breast cancer is associated with an epigenetic switch from H3K27me3 to H3K27Ac at the IGFBP5 promoter and IGFBP5 upregulation. KDM6B or IGFBP5 inhibition re-sensitizes resistant cells, demonstrating dependency on the KDM6B-IGFBP5 axis. KDM6B overexpression/inhibition; H3K27me3 and H3K27Ac ChIP at IGFBP5 promoter; EZH2 inhibitor; IGFBP5 siRNA; apoptosis assays in PI3K inhibitor-resistant cells Molecular cancer therapeutics High 29925528
2018 IGFBP-5 promotes pulmonary fibrosis by increasing production of ECM genes (collagen, fibronectin), upregulating pro-fibrotic CTGF, and increasing lysyl oxidase (LOX) expression in primary human lung fibroblasts; it also promotes its own expression, creating a positive feedback loop. These effects were demonstrated with both exogenous and adenovirally expressed IGFBP-5, including in human lung organ culture. Exogenous recombinant IGFBP-5 treatment; adenoviral IGFBP-5 expression; IGFBP-5 siRNA; ECM gene expression (collagen, fibronectin); CTGF and LOX expression; human lung organ culture Frontiers in endocrinology Medium 30374330
2019 PKNOX2 transcriptionally activates IGFBP5 by directly binding to the IGFBP5 promoter (demonstrated by ChIP-PCR). IGFBP5 knockdown partially abrogated the tumor-suppressive effects of PKNOX2 in gastric cancer cells, and IGFBP5 promoted PKNOX2-mediated p53 upregulation, placing IGFBP5 downstream of PKNOX2 in a PKNOX2→IGFBP5→p53 tumor suppressor pathway. ChIP-PCR for PKNOX2 binding to IGFBP5 promoter; IGFBP5 siRNA rescue; PKNOX2 overexpression/knockdown; p53 target gene expression; xenograft model Oncogene Medium 30745575
2019 Mybbp1a forms a complex with DNMT1 and induces hypermethylation of CpG islands in the IGFBP5 promoter, suppressing IGFBP5 secretion and thereby activating the IGF1/AKT signaling pathway to promote HCC progression. Mybbp1a suppression leads to IGFBP5 promoter hypomethylation, increased IGFBP5, and IGF1/AKT pathway inhibition. Co-IP (Mybbp1a-DNMT1 complex); ChIP; bisulfite sequencing; pyrosequencing of IGFBP5 CpG islands; Mybbp1a knockdown in HCC cells and xenografts EBioMedicine Medium 31109829
2022 IGFBP5 promotes diabetic kidney disease inflammation by activating the transcription factor EGR1, which increases PFKFB3 expression in glomerular endothelial cells, thereby enhancing glycolysis (increased lactate and ECAR). PFKFB3 mutation attenuated renal inflammation in DKD mice, placing IGFBP5 upstream of EGR1-PFKFB3-mediated metabolic reprogramming. IGFBP5 ablation in diabetic mice; EGR1 and PFKFB3 expression assays; extracellular acidification rate (ECAR) measurement; lactate measurement; PFKFB3 mutant rescue in vivo Cell death & disease Medium 35418167
2023 IGFBP5 is a ligand for the receptor tyrosine kinase-like orphan receptor 1 (ROR1). IGFBP5 binding to ROR1 facilitates ROR1/HER2 heterodimer formation, leading to CREB-mediated upregulation of ETV5 and FBXW9, thereby promoting glioblastoma stem-like cell (GSC) invasion and tumorigenesis both in vitro and in patient-derived xenograft models. Co-IP/binding assays (IGFBP5-ROR1); ROR1/HER2 heterodimer pulldown; IGFBP5 knockdown/overexpression in GSCs; CREB reporter; ETV5/FBXW9 expression; patient-derived xenograft invasion model; CRISPR/Cas9 IGFBP5 gene editing via nanocapsule delivery Nature communications High 36949068
2007 The MN1 oncoprotein transcriptionally activates the IGFBP5 promoter through a CACCC-rich consensus sequence located ~140 bp upstream of the transcription start site. Retinoic acid induction of the IGFBP5 promoter depends on co-expressed MN1 in Hep3B cells. The leukemia-associated MN1TEL fusion protein activates the promoter but cannot cooperate with retinoic acid. IGFBP5 promoter-luciferase reporter; promoter deletion analysis; oligonucleotide selection assay; MN1 and MN1TEL cotransfection; retinoic acid treatment Journal of molecular endocrinology Medium 17242174
2010 Curcumin activates p38 MAP kinase, which in turn activates the C/EBPα transcription factor that binds a CACCC-containing element (nt -71 to -59) in the IGFBP5 promoter to drive IGFBP5 expression in oral keratinocytes. ChIP confirmed increased C/EBPα binding at this region in the presence of curcumin; SB203580 (p38 inhibitor) blocked curcumin-induced IGFBP5 upregulation. IGFBP5 promoter deletion mapping; ChIP for C/EBPα binding; p38 inhibitor (SB203580); MKK6 overexpression; xenograft tumorigenesis assay International journal of cancer Medium 20127863
2017 BCOR forms a protein complex with the histone demethylase KDM6B and raises H3K27 methylation at the IGFBP5 promoter, thereby negatively regulating IGFBP5 expression in mesenchymal stem cells. This was demonstrated by Co-IP and ChIP assays. Co-IP (BCOR-KDM6B complex); ChIP for H3K27me3 at IGFBP5 promoter; BCOR knockdown; IGFBP5 rescue Stem cell research & therapy Medium 28962660
2016 Activated coagulation factor X (FXa) induces endothelial cell senescence through upregulation of IGFBP-5 (along with EGR-1, p53, p16INK4a). siRNA knockdown of IGFBP-5 decreased FXa-induced senescence and restored cell proliferation. In a mouse hindlimb ischemia model, FXa inhibited neovascularization, an effect reversed by the FXa inhibitor rivaroxaban. FXa treatment of HUVECs; RT-qPCR array; IGFBP-5 siRNA; senescence-associated beta-galactosidase assay; ischemic hindlimb mouse model Scientific reports Medium 27752126
2025 IGFBP5 promotes endothelial-to-mesenchymal transition (EndoMT) and renal fibrosis in diabetic nephropathy by increasing glycolysis, which elevates histone H3K18 lactylation, activating the NLRP3 inflammasome. IGFBP5 knockdown in glomerular endothelial cells and DN mouse models reduced glycolysis, H3K18 lactylation, NLRP3 inflammasome activation, EndoMT, and renal fibrosis. IGFBP5 siRNA knockdown in glomerular endothelial cells and DN mouse model; glycolysis measurement; H3K18 lactylation assay; NLRP3 inflammasome inhibitor (MCC950); EndoMT markers; fibrosis assessment in vivo Cellular and molecular life sciences Medium 40423799

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 Regulation of the IGFBP-5 and MMP-13 genes by the microRNAs miR-140 and miR-27a in human osteoarthritic chondrocytes. BMC musculoskeletal disorders 205 19948051
2006 Insulin-like growth factor-binding protein-5 (IGFBP-5): a critical member of the IGF axis. The Biochemical journal 187 16526944
2004 Insulin-like growth factor-binding protein 5 (Igfbp5) compromises survival, growth, muscle development, and fertility in mice. Proceedings of the National Academy of Sciences of the United States of America 157 15010534
1998 Structure of the IGF-binding domain of the insulin-like growth factor-binding protein-5 (IGFBP-5): implications for IGF and IGF-I receptor interactions. The EMBO journal 156 9822601
2008 IGFBP-5 regulates muscle cell differentiation by binding to IGF-II and switching on the IGF-II auto-regulation loop. The Journal of cell biology 114 18762576
2017 Uterine Inflammatory Myofibroblastic Tumors Frequently Harbor ALK Fusions With IGFBP5 and THBS1. The American journal of surgical pathology 107 28490045
2002 Insulin-like growth factor binding protein-5 (IGFBP-5) induces premature cell death in the mammary glands of transgenic mice. Development (Cambridge, England) 105 12223411
2015 MiR-204-5p suppresses cell proliferation by inhibiting IGFBP5 in papillary thyroid carcinoma. Biochemical and biophysical research communications 101 25603050
2012 c-Src and IL-6 inhibit osteoblast differentiation and integrate IGFBP5 signalling. Nature communications 100 22252554
2014 Evidence that breast cancer risk at the 2q35 locus is mediated through IGFBP5 regulation. Nature communications 97 25248036
2012 The STAT3-IGFBP5 axis is critical for IL-6/gp130-induced premature senescence in human fibroblasts. Cell cycle (Georgetown, Tex.) 93 22374671
2001 The interaction of insulin-like growth factor-I with the N-terminal domain of IGFBP-5. The EMBO journal 92 11447105
2002 Intrinsic actions of IGFBP-3 and IGFBP-5 on Hs578T breast cancer epithelial cells: inhibition or accentuation of attachment and survival is dependent upon the presence of fibronectin. Journal of cell science 91 12376561
2012 IGFBP5 induces cell adhesion, increases cell survival and inhibits cell migration in MCF-7 human breast cancer cells. Journal of cell science 81 22328518
2022 IGFBP5 promotes diabetic kidney disease progression by enhancing PFKFB3-mediated endothelial glycolysis. Cell death & disease 77 35418167
2017 Local application of IGFBP5 protein enhanced periodontal tissue regeneration via increasing the migration, cell proliferation and osteo/dentinogenic differentiation of mesenchymal stem cells in an inflammatory niche. Stem cell research & therapy 77 28962660
2016 Age-related changes in miR-143-3p:Igfbp5 interactions affect muscle regeneration. Aging cell 77 26762731
2015 Insulin-like growth factor binding protein 5 (IGFBP5) functions as a tumor suppressor in human melanoma cells. Oncotarget 76 26010068
2015 Demethylation of IGFBP5 by Histone Demethylase KDM6B Promotes Mesenchymal Stem Cell-Mediated Periodontal Tissue Regeneration by Enhancing Osteogenic Differentiation and Anti-Inflammation Potentials. Stem cells (Dayton, Ohio) 75 25827480
2013 DOG1 regulates growth and IGFBP5 in gastrointestinal stromal tumors. Cancer research 69 23576565
2004 Partitioning of IGFBP-5 actions in myogenesis: IGF-independent anti-apoptotic function. Journal of cell science 66 15075235
2018 Flow-dependent epigenetic regulation of IGFBP5 expression by H3K27me3 contributes to endothelial anti-inflammatory effects. Theranostics 65 29896299
2018 IGFBP-5 Promotes Fibrosis via Increasing Its Own Expression and That of Other Pro-fibrotic Mediators. Frontiers in endocrinology 65 30374330
2016 Secreted IGFBP5 mediates mTORC1-dependent feedback inhibition of IGF-1 signalling. Nature cell biology 63 26854565
2002 Insulin-like growth factor-binding protein-5 (IGFBP-5) stimulates growth and IGF-I secretion in human intestinal smooth muscle by Ras-dependent activation of p38 MAP kinase and Erk1/2 pathways. The Journal of biological chemistry 63 11923300
1995 Age-related changes in IGFBP-4 and IGFBP-5 levels in human serum and bone: implications for bone loss with aging. Progress in growth factor research 60 8817691
2007 Insulin-like growth factor binding proteins IGFBP3, IGFBP4, and IGFBP5 predict endocrine responsiveness in patients with ovarian cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 59 17332286
1999 Androgen receptor up-regulates insulin-like growth factor binding protein-5 (IGFBP-5) expression in a human prostate cancer xenograft. Endocrinology 59 10218991
2009 IGF-independent effects of insulin-like growth factor binding protein-5 (Igfbp5) in vivo. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 57 19332648
2018 miR-143-3p regulates cell proliferation and apoptosis by targeting IGF1R and IGFBP5 and regulating the Ras/p38 MAPK signaling pathway in rheumatoid arthritis. Experimental and therapeutic medicine 56 29581736
2013 IGFBP5 domains exert distinct inhibitory effects on the tumorigenicity and metastasis of human osteosarcoma. Cancer letters 56 23665505
2009 The pro-fibrotic factor IGFBP-5 induces lung fibroblast and mononuclear cell migration. American journal of respiratory cell and molecular biology 56 19131643
2008 IGFBP2 and IGFBP5 overexpression correlates with the lymph node metastasis in T1 breast carcinomas. The breast journal 55 18373644
1996 Insulin-like growth factor-binding proteins (IGFBP)-4, -5, and -6 in the benign and malignant human prostate: IGFBP-5 messenger ribonucleic acid localization differs from IGFBP-5 protein localization. The Journal of clinical endocrinology and metabolism 55 8855838
1994 Signaling by insulin-like growth factors in paralyzed skeletal muscle: rapid induction of IGF1 expression in muscle fibers and prevention of interstitial cell proliferation by IGF-BP5 and IGF-BP4. The Journal of neuroscience : the official journal of the Society for Neuroscience 53 7514217
2009 The subcellular localization of IGFBP5 affects its cell growth and migration functions in breast cancer. BMC cancer 50 19341485
2016 miR-143 regulates proliferation and differentiation of bovine skeletal muscle satellite cells by targeting IGFBP5. In vitro cellular & developmental biology. Animal 49 27800570
2004 Sustained elevation of pulsatile growth hormone (GH) secretion and insulin-like growth factor I (IGF-I), IGF-binding protein-3 (IGFBP-3), and IGFBP-5 concentrations during 30-day continuous subcutaneous infusion of GH-releasing peptide-2 in older men and women. The Journal of clinical endocrinology and metabolism 49 15126555
2019 PKNOX2 suppresses gastric cancer through the transcriptional activation of IGFBP5 and p53. Oncogene 48 30745575
2014 Insulin-like growth factor binding protein 5 (IGFBP5) mediates methamphetamine-induced dopaminergic neuron apoptosis. Toxicology letters 48 25127757
2023 IGFBP5 is an ROR1 ligand promoting glioblastoma invasion via ROR1/HER2-CREB signaling axis. Nature communications 47 36949068
2005 Silencing of endogenous IGFBP-5 by micro RNA interference affects proliferation, apoptosis and differentiation of neuroblastoma cells. Cell death and differentiation 47 15618969
2000 Insulin-like growth factor binding protein-5 (IGFBP-5) potentially regulates programmed cell death and plasminogen activation in the mammary gland. Advances in experimental medicine and biology 47 10959408
2014 Transcriptomic profiling suggests a role for IGFBP5 in premature senescence of endothelial cells after chronic low dose rate irradiation. International journal of radiation biology 46 24646080
2016 IGFBP5 enhances osteogenic differentiation potential of periodontal ligament stem cells and Wharton's jelly umbilical cord stem cells, via the JNK and MEK/Erk signalling pathways. Cell proliferation 45 27484838
2010 Curcumin upregulates insulin-like growth factor binding protein-5 (IGFBP-5) and C/EBPalpha during oral cancer suppression. International journal of cancer 44 20127863
2002 Vitronectin binding to IGF binding protein-5 (IGFBP-5) alters IGFBP-5 modulation of IGF-I actions. Endocrinology 44 11751588
2008 Insulin-like growth factor binding protein-5 (IGFBP-5) suppresses the tumourigenesis of head and neck squamous cell carcinoma. The Journal of pathology 43 18085517
2002 Regulation of IGFBP-5 expression during tumourigenesis and differentiation of oral keratinocytes. The Journal of pathology 43 12375264
2005 Ras-association domain family 1 protein, RASSF1C, is an IGFBP-5 binding partner and a potential regulator of osteoblast cell proliferation. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 42 16007340
2018 KDM6B Counteracts EZH2-Mediated Suppression of IGFBP5 to Confer Resistance to PI3K/AKT Inhibitor Treatment in Breast Cancer. Molecular cancer therapeutics 41 29925528
2017 Dysregulated DNA Methyltransferase 3A Upregulates IGFBP5 to Suppress Trophoblast Cell Migration and Invasion in Preeclampsia. Hypertension (Dallas, Tex. : 1979) 40 28049695
2016 microRNA -140-5p inhibits colorectal cancer invasion and metastasis by targeting ADAMTS5 and IGFBP5. Stem cell research & therapy 40 27906093
2004 The role of IGFBP-5 in mammary gland development and involution. Domestic animal endocrinology 40 15451073
2019 circPIP5K1A serves as a competitive endogenous RNA contributing to ovarian cancer progression via regulation of miR-661/IGFBP5 signaling. Journal of cellular biochemistry 39 31452245
2013 IGFBP5 mediates high glucose-induced cardiac fibroblast activation. Journal of molecular endocrinology 39 23417767
2009 Role of insulin-like growth factor-binding protein 5 (IGFBP5) in organismal and pancreatic beta-cell growth. Molecular endocrinology (Baltimore, Md.) 39 19897600
2005 Differential expression of IGF system components in proliferating vs. differentiating growth plate chondrocytes: the functional role of IGFBP-5. American journal of physiology. Endocrinology and metabolism 39 16204335
2020 IGFBP5 increases cell invasion and inhibits cell proliferation by EMT and Akt signaling pathway in Glioblastoma multiforme cells. Cell division 38 32127912
2005 Segmental Igfbp5 expression is specifically associated with the bent structure of zigzag hairs. Mechanisms of development 38 16024235
2015 Dysregulated IGFBP5 expression causes axon degeneration and motoneuron loss in diabetic neuropathy. Acta neuropathologica 37 26025657
2010 Tumor-associated retinal astrocytes promote retinoblastoma cell proliferation through production of IGFBP-5. The American journal of pathology 37 20508032
1998 IGFBP-3 and IGFBP-5 production by human intestinal muscle: reciprocal regulation by endogenous TGF-beta1. The American journal of physiology 37 9843764
2001 Roles of insulin-like growth factor-I (IGF-I) and IGF-I binding protein-2 (IGFBP2) and -5 (IGFBP5) in developing chick limbs. Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society 36 11914022
2002 Signalling pathways involved in the direct effects of IGFBP-5 on breast epithelial cell attachment and survival. Journal of cellular biochemistry 34 11835403
2000 Differential effects of IGF-binding proteins, IGFBP-3 and IGFBP-5, on IGF-I action and binding to cell membranes of immortalized human chondrocytes. The Journal of endocrinology 32 10856880
2016 The C-terminus of IGFBP-5 suppresses tumor growth by inhibiting angiogenesis. Scientific reports 31 28008951
2015 Stromal cells promote anti-estrogen resistance of breast cancer cells through an insulin-like growth factor binding protein 5 (IGFBP5)/B-cell leukemia/lymphoma 3 (Bcl-3) axis. Oncotarget 31 26515727
2006 Overexpression of IGFBP5, but not IGFBP3, correlates with the histologic grade of human diffuse glioma: a tissue microarray and immunohistochemical study. Technology in cancer research & treatment 31 16700616
2020 IGFBP5 modulates lipid metabolism and insulin sensitivity through activating AMPK pathway in non-alcoholic fatty liver disease. Life sciences 30 32585242
2009 IGFBP-5 induces epithelial and fibroblast responses consistent with the fibrotic response. Biochemical Society transactions 30 19614612
2021 Single cell RNA sequencing identifies IGFBP5 and QKI as ciliated epithelial cell genes associated with severe COPD. Respiratory research 29 33823868
2013 IGFBP-5 enhances epithelial cell adhesion and protects epithelial cells from TGFβ1-induced mesenchymal invasion. The international journal of biochemistry & cell biology 29 24120850
2016 An intergenic risk locus containing an enhancer deletion in 2q35 modulates breast cancer risk by deregulating IGFBP5 expression. Human molecular genetics 28 27402876
2016 Activated Factor X Induces Endothelial Cell Senescence Through IGFBP-5. Scientific reports 28 27752126
2019 IGFBP5 promotes angiogenic and neurogenic differentiation potential of dental pulp stem cells. Development, growth & differentiation 27 31599466
2018 Knockdown of lncRNA UCA1 inhibits proliferation and invasion of papillary thyroid carcinoma through regulating miR-204/IGFBP5 axis. OncoTargets and therapy 27 30425512
2005 Insulin-like growth factor binding protein (IGFBP)-3 and IGFBP-5 mediate TGF-beta- and myostatin-induced suppression of proliferation in porcine embryonic myogenic cell cultures. Experimental cell research 27 16214131
2003 Differential expression of IGFBP-5 and two human ESTs in thyroid glands with goiter, adenoma and papillary or follicular carcinomas. Cancer letters 26 12618333
1997 Serum insulin-like growth factor binding protein (IGFBP)-4 and IGFBP-5 levels in aging and age-associated diseases. Endocrine 25 9449039
2020 MiR-193b inhibits autophagy and apoptosis by targeting IGFBP5 in high glucose-induced trophoblasts. Placenta 24 33010605
2019 Targeting Mybbp1a suppresses HCC progression via inhibiting IGF1/AKT pathway by CpG islands hypo-methylation dependent promotion of IGFBP5. EBioMedicine 24 31109829
2003 Hormonal control of IGF-binding protein (IGFBP)-5 and IGFBP-2 secretion during differentiation of the HC11 mouse mammary epithelial cell line. Journal of molecular endocrinology 24 12914536
2022 Biological effects and regulation of IGFBP5 in breast cancer. Frontiers in endocrinology 23 36093095
2017 MiR-137 inhibited cell proliferation and migration of vascular smooth muscle cells via targeting IGFBP-5 and modulating the mTOR/STAT3 signaling. PloS one 23 29016699
2015 Identification of Differentially Expressed IGFBP5-Related Genes in Breast Cancer Tumor Tissues Using cDNA Microarray Experiments. Genes 23 26569312
2008 Genetic variation in IGFBP2 and IGFBP5 is associated with breast cancer in populations of African descent. Human genetics 23 18210156
2018 Expression of Insulin-Like Growth Factor Binding Protein-5 (IGFBP5) Reverses Cisplatin-Resistance in Esophageal Carcinoma. Cells 22 30241323
1993 Molecular cloning of IGFBP-5 from SCLC cell lines and expression of IGFBP-4, IGFBP-5 and IGFBP-6 in lung cancer cell lines and primary tumours. European journal of cancer (Oxford, England : 1990) 22 7692907
2022 Exosome-Encapsulated microRNA-140-5p Alleviates Neuronal Injury Following Subarachnoid Hemorrhage by Regulating IGFBP5-Mediated PI3K/AKT Signaling Pathway. Molecular neurobiology 20 36129637
2014 Clinical significance of miR-140-5p and miR-193b expression in patients with breast cancer and relationship to IGFBP5. Genetics and molecular biology 20 25983620
2012 Mammary tumor regression elicited by Wnt signaling inhibitor requires IGFBP5. Cancer research 20 22307840
2019 Microstructural changes in the brain mediate the association of AK4, IGFBP5, HSPB2, and ITPK1 with cognitive decline. Neurobiology of aging 19 31479860
2017 IGF1R activation and the in vitro antiproliferative efficacy of IGF1R inhibitor are inversely correlated with IGFBP5 expression in bladder cancer. BMC cancer 19 28882129
2025 IGFBP5 promotes EndoMT and renal fibrosis through H3K18 lactylation in diabetic nephropathy. Cellular and molecular life sciences : CMLS 18 40423799
2021 Identification of Impacted Pathways and Transcriptomic Markers as Potential Mediators of Pulmonary Fibrosis in Transgenic Mice Expressing Human IGFBP5. International journal of molecular sciences 18 34830489
2019 IGFBP5 suppresses oleate-induced intramyocellular lipids deposition and enhances insulin signaling. Journal of cellular physiology 18 30684263
2015 Upregulation of miR-197 inhibits cell proliferation by directly targeting IGFBP5 in human uterine leiomyoma cells. In vitro cellular & developmental biology. Animal 18 25990270
2007 The MN1 oncoprotein activates transcription of the IGFBP5 promoter through a CACCC-rich consensus sequence. Journal of molecular endocrinology 18 17242174
2006 Prolactin inhibits cell loss and decreases matrix metalloproteinase expression in the involuting mouse mammary gland but fails to prevent cell loss in the mammary glands of mice expressing IGFBP-5 as a mammary transgene. Journal of molecular endocrinology 18 16720715

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