Affinage

FGFR1

Fibroblast growth factor receptor 1 · UniProt P11362

Length
822 aa
Mass
91.9 kDa
Annotated
2026-06-09
100 papers in source corpus 32 papers cited in narrative 32 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

FGFR1 is a ligand-activated receptor tyrosine kinase that couples extracellular growth-factor cues to the RAS-MAPK/ERK, PI3K-AKT, PLCγ/IP3-calcium, and STAT signaling cascades to control proliferation, differentiation, migration, and tissue patterning (PMID:10918587, PMID:21479780). Receptor output is set by its ligand repertoire and co-receptors: canonical FGF2 drives ERK activation (PMID:30875802), FGF21 requires the co-receptor βKlotho (KLB) to engage FGFR1 with high affinity for the adipose response (PMID:22442730), and non-canonical ligands including Gremlin1 (binding at an interface distinct from FGF1) and the thrombomodulin domain rTMD23 also activate FGFR1 (PMID:35624341, PMID:25388665). Kinase activity is dispensable for receptor internalization, which is triggered purely by dimerization/clustering and proceeds through clathrin- and dynamin-dependent endocytosis (PMID:28769084, PMID:32511887). Receptor signaling is further tuned post-translationally: Nedd4-1 binds activated FGFR1 through a non-canonical motif and ubiquitylates it to drive endocytic downregulation (PMID:21765395), while SUMOylation (reversed by SENP1) restrains kinase activation by modulating dimerization and PTPRG interaction and redirects FRS2α recruitment toward VEGFR2, switching endothelial cells between FGF/FGFR1 and VEGFA/VEGFR2 angiogenic signaling (PMID:35733256). Beyond the membrane, an FGF-stimulated, Granzyme B-cleaved fragment of FGFR1 translocates to the nucleus, where it occupies transcription start sites in complex with phosphorylated RNA Pol II and FOXA1 to reprogram transcription and confer endocrine resistance in breast cancer—activity insensitive to FGFR kinase inhibitors (PMID:22665522, PMID:34011560). In oncology FGFR1 acts through an ERK1/2-SOX2 axis to drive EMT and invasion and through PLCγ to confer radioresistance (PMID:29858603, PMID:26896280), and FGFR1 amplification supports prostate cancer progression and metastasis (PMID:23576558). Developmentally, FGFR1 is required for primitive endoderm specification and exit from pluripotency, telencephalic midline and commissural formation, and cerebellar morphogenesis (PMID:28552557, PMID:16309667, PMID:22578469). A dominant-negative secreted truncation underlies a Kallmann syndrome FGFR1 mutation that suppresses wild-type receptor ERK signaling (PMID:28411082).

Mechanistic history

Synthesis pass · year-by-year structured walk · 25 steps
  1. 2000 High

    Established that the FGFR1 kinase domain, when constitutively active and membrane-targeted, is sufficient to engage a broad downstream signaling network and drive transformation and differentiation, defining its core effector outputs.

    Evidence Activating mutagenesis with transformation, neurite-outgrowth, and substrate-phosphorylation readouts in NIH3T3/PC12 cells

    PMID:10918587

    Open questions at the time
    • Does not address ligand- or co-receptor-dependent activation
    • Effector usage in physiological contexts not resolved
  2. 2001 Medium

    Showed FGFR1 phosphorylation and ERK activation are among the earliest signaling events after retinal detachment, placing the receptor at the front of an injury-response cascade.

    Evidence Western/immunoprecipitation and IHC in cat and rabbit retinal detachment models

    PMID:11328752

    Open questions at the time
    • Causality from FGF-2 inferred, not proven
    • Downstream functional consequence not established
  3. 2011 High

    Identified Nedd4-1 as a direct E3 ligase that ubiquitylates activated FGFR1 to drive endocytic downregulation, revealing a post-translational brake on receptor signaling with developmental consequences.

    Evidence Reciprocal Co-IP, ubiquitylation/endocytosis assays, recognition-motif deletion, and zebrafish patterning readouts

    PMID:21765395

    Open questions at the time
    • Structural basis of non-PY motif recognition not defined
    • Relative contribution versus other downregulation routes unknown
  4. 2011 Medium

    Demonstrated via a kinase-domain point mutant that loss of catalytic function abolishes both IP3/calcium and Ras/MAPK signaling and acts dominant-negatively, supporting receptor dimerization as the mechanism of dominant interference.

    Evidence W691R (hush puppy) mutagenesis with calcium and MAPK assays in heterozygous mice

    PMID:21479780

    Open questions at the time
    • Dominant-negative dimerization inferred, not directly visualized
    • Single mutant allele
  5. 2012 High

    Resolved the ligand-and-co-receptor logic of FGFR1 activation, showing FGF21 selectively engages FGFR1 via KLB to mediate adipose responses, distinguishing it from KLB-independent FGF1.

    Evidence Binding kinetics plus KLB/FGFR1 conditional knockout mice

    PMID:22442730

    Open questions at the time
    • Structural detail of the FGF21-FGFR1-KLB ternary complex not defined
    • Tissue-specific co-receptor availability not mapped
  6. 2012 High

    Uncovered a non-canonical pathway in which Granzyme B cleaves FGF-stimulated FGFR1 and the fragment traffics to the nucleus to control pro-migratory transcription, redefining FGFR1 as a direct transcriptional effector.

    Evidence Cleavage/nuclear-trafficking assays with Granzyme B inhibition, 3D model, and clinical breast cancer IHC

    PMID:22665522

    Open questions at the time
    • Nuclear target gene set only partially defined here
    • Mechanism of nuclear import not detailed
  7. 2014 High

    Defined FGFR1 as an autocrine regulator of FGF23 in bone, controlling its production both transcriptionally (PLCγ/MAPK) and translationally (PI3K/Akt), linking receptor signaling to mineral homeostasis.

    Evidence Osteocyte-specific Dmp1-Cre Fgfr1 deletion with promoter assays and pathway inhibitors

    PMID:25089825

    Open questions at the time
    • Upstream ligand in osteocytes not identified
    • Direct transcription factor mediating promoter activation unknown
  8. 2014 Medium

    Added thrombomodulin domain rTMD23 as a direct FGFR1 binder that activates the receptor to promote angiogenesis, broadening the non-canonical ligand repertoire.

    Evidence Co-precipitation, SPR binding kinetics, siRNA/inhibitor blockade, and ischemic hindlimb model

    PMID:25388665

    Open questions at the time
    • Physiological relevance of TM-FGFR1 interaction unclear
    • Binding interface not mapped
  9. 2017 Medium

    Showed FGFR1 dimerization alone is sufficient to trigger clathrin/dynamin-dependent endocytosis independent of kinase activity, separating receptor internalization from catalytic signaling.

    Evidence Valency-engineered antibody fragments with endocytic-pathway inhibitors and kinase-dead receptor

    PMID:28769084

    Open questions at the time
    • Adaptor proteins linking dimers to clathrin not identified
    • Single-lab antibody system
  10. 2017 High

    Established distinct, non-redundant roles for FGFR1 over FGFR2 in primitive endoderm formation and exit from pluripotency, defining receptor-specific functions in early development.

    Evidence Reporter knockin lines and conditional double-knockout mice with ESC differentiation assays

    PMID:28552557

    Open questions at the time
    • Downstream effectors distinguishing FGFR1 from FGFR2 not defined
    • Ligand source in blastocyst not resolved
  11. 2017 Medium

    Identified FOXC1 as a transcriptional driver of the FGFR1-IIIc isoform during TGFβ1-induced EMT, linking transcriptional control of receptor isoform choice to migratory behavior.

    Evidence ChIP, luciferase reporter, FOXC1 knockdown/overexpression, and FGFR1-rescued 3D migration

    PMID:28684636

    Open questions at the time
    • Isoform-specific signaling differences not dissected
    • Single context (EMT) tested
  12. 2017 Medium

    Showed FGFR1 inhibition induces ERK/MAPK-dependent, beclin-1-mediated autophagy as a survival response in FGFR1-amplified lung cancer, rationalizing combination with autophagy inhibition.

    Evidence LC3/beclin-1 assays, constitutively active MEK1, beclin-1 RNAi, and FGFR1 shRNA/AZD4547

    PMID:28558758

    Open questions at the time
    • In vivo relevance of autophagy response not established here
    • Single-lab data
  13. 2018 High

    Defined an FGFR1-ERK1/2-SOX2 axis driving EMT, proliferation, and invasion in FGFR1-amplified lung cancer, establishing a transcription-factor effector for the oncogenic phenotype.

    Evidence FGF2/AZD4547, constitutively active ERK2, SOX2 knockdown, and xenograft models

    PMID:29858603

    Open questions at the time
    • Direct ERK-SOX2 regulatory link mechanism not detailed
    • Generality beyond lung cancer untested
  14. 2018 Medium

    Showed the gatekeeper V561M mutation confers FGFR inhibitor resistance through elevated STAT3 signaling, identifying a targetable bypass downstream of mutant FGFR1.

    Evidence Kinase binding assays, CyTOF, STAT3 shRNA rescue of AZD4547 sensitivity

    PMID:30257990

    Open questions at the time
    • Mechanism coupling V561M to STAT3 not defined
    • Single-lab cell models
  15. 2019 High

    Mapped nuclear FGFR1 genome-wide occupancy and its interaction with phospho-RNA Pol II and FOXA1, establishing it as a kinase-inhibitor-resistant transcriptional driver of endocrine resistance.

    Evidence ChIP-seq, RNA-seq, MS interactome, FOXA1 siRNA, and xenograft

    PMID:34011560

    Open questions at the time
    • How FGFR1 is recruited to specific TSS beyond FOXA1 unclear
    • Structural basis of Pol II association unknown
  16. 2019 Medium

    Used compartment-targeted optogenetics to show only membrane-associated FGFR1 kinase, via ERK, drives neuronal differentiation, while nuclear FGFR1 kinase produces no signaling change, dissociating nuclear function from kinase activity.

    Evidence LOV-domain FGFR1 fusions targeted to membrane/cytoplasm/nucleus with signaling and neurite readouts

    PMID:30875802

    Open questions at the time
    • Cell-type dependence (PC12 vs HEK293) unexplained
    • Does not address ligand-driven nuclear translocation
  17. 2019 Medium

    Identified the catalytically dead receptor PTK7 as a direct extracellular-domain partner that transactivates FGFR1 and is required for full receptor phosphorylation and oncogenic signaling.

    Evidence Co-IP, colocalization, PTK7 siRNA with phosphorylation and oncogenic-phenotype assays in ESCC cells

    PMID:31490704

    Open questions at the time
    • Structural mechanism of PTK7-driven transactivation unknown
    • Single cancer context
  18. 2019 Medium

    Showed FGFR1 amplifies tumor angiogenesis by MAPK-dependent VEGF secretion and an autocrine VEGF-VEGFR1-AKT loop, supporting dual FGFR1/VEGFR1 targeting.

    Evidence FGFR1 knockout, VEGF secretion assays, MEK/FGFR inhibitors, and in vivo angiogenesis

    PMID:29970903

    Open questions at the time
    • Direct vs indirect VEGF regulation not separated
    • Single-lab models
  19. 2019 Low

    Proposed a reciprocal YAP1-FGFR1 regulatory loop sustaining self-renewal in FGFR1-amplified lung cancer.

    Evidence TEAD promoter analysis, YAP1 knockdown/overexpression, and orthotopic model

    PMID:29452146

    Open questions at the time
    • TEAD binding to FGFR1 promoter not confirmed by direct ChIP
    • Loop directionality not rigorously established
  20. 2020 Medium

    Refined the endocytosis model by showing higher-order FGFR1 clustering engages an additional dynamin-dependent, clathrin-independent internalization route, all kinase-independent.

    Evidence Tetravalent vs bivalent antibodies with route-specific inhibitors and kinase-dead FGFR1

    PMID:32511887

    Open questions at the time
    • Molecular machinery of clathrin-independent route unidentified
    • Physiological clustering triggers unknown
  21. 2020 High

    Placed FGFR1 in a Piezo1-FGF1 mechanotransduction feedback loop controlling preadipocyte differentiation, connecting mechanical sensing to adipogenesis.

    Evidence Adipocyte-specific Piezo1 knockout mice with FGF1 secretion and FGFR1 activation assays under high-fat diet

    PMID:32385276

    Open questions at the time
    • FGFR1 effector pathway in preadipocytes not dissected
    • Other Piezo1-released factors not excluded
  22. 2022 High

    Defined SUMOylation (writer machinery; SENP1 eraser) as a switch restraining FGFR1 kinase activation and rerouting FRS2α to VEGFR2, balancing FGF/FGFR1 versus VEGFA/VEGFR2 angiogenic signaling.

    Evidence SUMO-site mutagenesis, SENP1 manipulation, dimerization/PTPRG/FRS2α assays, and SUMO-defective knockin mice

    PMID:35733256

    Open questions at the time
    • Stoichiometry and dynamics of SUMOylation in vivo not quantified
    • Crosstalk with ubiquitylation not resolved
  23. 2022 High

    Identified Gremlin1 as a non-canonical FGFR1 ligand binding at an interface distinct from FGF1 to activate MAPK and drive prostate cancer lineage plasticity and castration resistance.

    Evidence Co-IP, structural docking, mutagenesis, and in vivo anti-Gremlin1 antibody with ADT

    PMID:35624341

    Open questions at the time
    • High-resolution structure of the Gremlin1-FGFR1 complex not solved
    • Co-receptor requirements unknown
  24. 2023 Medium

    Showed VEGF-B directly binds FGFR1, drives FGFR1/VEGFR1 heterodimer formation, and suppresses FGF2-induced ERK, defining a negative-regulatory ligand-receptor cross-interaction in angiogenesis.

    Evidence Direct binding, Co-IP for heterodimer, ERK Western, and in vitro/in vivo tumor models

    PMID:37591843

    Open questions at the time
    • Mechanism by which heterodimerization blunts signaling unclear
    • Single-lab study
  25. 2023 Medium

    Placed ROCK2 downstream of endothelial FGFR1, with FGFR1 loss derepressing ROCK2 to increase vascular permeability and inflammation in lung injury, defining a barrier-protective signaling axis.

    Evidence Endothelial-specific Fgfr1 knockout, HUVEC knockdown, ROCK2 activity assays, and ROCK2-inhibitor rescue

    PMID:36969192

    Open questions at the time
    • Direct biochemical link between FGFR1 and ROCK2 regulation unknown
    • Single injury model

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the membrane, ubiquitylation, SUMOylation, endocytic, and nuclear FGFR1 modes are integrated into a single regulatory program—and how ligand/co-receptor identity selects among them—remains unresolved.
  • No unified model linking post-translational marks to fate choice between degradation, recycling, and nuclear translocation
  • Crosstalk between ubiquitylation and SUMOylation not mapped
  • Structural basis distinguishing canonical from non-canonical ligand engagement incomplete

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 4 GO:0060089 molecular transducer activity 3 GO:0140110 transcription regulator activity 2 GO:0140657 ATP-dependent activity 1
Localization
GO:0005886 plasma membrane 4 GO:0005634 nucleus 2 GO:0031410 cytoplasmic vesicle 2
Pathway
R-HSA-1266738 Developmental Biology 3 R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 3 R-HSA-5653656 Vesicle-mediated transport 3 R-HSA-74160 Gene expression (Transcription) 2
Partners
FOXA1FRS2GREM1KLBNEDD4PTK7PTPRGVEGFR1

Evidence

Reading pass · 32 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 Constitutively active FGFR1 kinase domain (activation loop mutation K→E, analogous to TDII), when targeted to the plasma membrane by a myristylation signal, transforms NIH3T3 cells, induces neurite outgrowth in PC12 cells, and activates Shp2, PLCγ, MAPK, Stat1, Stat3, and PI-3 kinase downstream. Activated receptor mutagenesis, cell transformation assay, neurite outgrowth assay, immunoprecipitation/Western blot for downstream signaling Oncogene High 10918587
2011 Nedd4-1 (E3 ubiquitin ligase) directly binds activated FGFR1 via its WW3 domain interacting with a non-canonical non-PY motif on FGFR1, ubiquitylates it, and promotes its endocytosis. Deletion of the Nedd4-1 recognition motif (FGFR1-Δ6) abolishes ubiquitylation, impairs receptor endocytosis, and sustains downstream signaling (FRS2α, Akt, Erk1/2, PLCγ phosphorylation), promoting neuronal differentiation and disrupting anterior brain patterning in zebrafish. Co-immunoprecipitation, ubiquitylation assay, receptor endocytosis assay, Western blot for downstream signaling, neural stem cell differentiation assay, zebrafish embryo expression The EMBO journal High 21765395
2012 FGF-10-stimulated FGFR1 is cleaved by Granzyme B and the resulting fragment traffics to the nucleus, where it regulates specific target genes that promote cell migration. Blocking Granzyme B activity prevents nuclear FGFR1 trafficking and abrogates the FGF-stimulated pro-migratory effect. Nuclear FGFR1 was confirmed in invading cells in clinical breast cancer material and a 3D model. FGFR1 cleavage/nuclear trafficking assay, Granzyme B inhibition, target gene identification, 3D breast cancer model, clinical tissue analysis (IHC) The Journal of cell biology High 22665522
2012 FGF21 binds FGFR1 with much higher affinity than FGFR4 in the presence of co-receptor KLB (betaKlotho), whereas FGF19 binds both FGFR1 and FGFR4/KLB complexes with comparable affinity. KLB is an indispensable mediator for FGF19/FGF21 binding to FGFRs (but not required for FGF1 binding). Ablation of KLB or FGFR1 blunts the adipose tissue response to FGF21. Quantitative binding kinetics (surface plasmon resonance/direct binding assay), downstream signal transduction assays, conditional knockout mice (KLB/FGFR1 ablation) PloS one High 22442730
2014 Osteocyte-specific deletion of Fgfr1 (via Dmp1-Cre) reduces FGF23 expression in bone and circulating FGF23 levels. FGFR1 activation in osteoblasts stimulates FGF23 promoter activity via PLCγ and MAPK pathways and also promotes FGF23 translation via PI3K/Akt—thus FGFR1 regulates FGF23 by both transcriptional and post-transcriptional mechanisms. Conditional knockout (Dmp1-Cre;Fgfr1flox), FGF23 promoter activity assay, pharmacological inhibition of PLCγ/MAPK/PI3K, Western blot, qPCR PloS one High 25089825
2017 Antibody-induced dimerization of FGFR1 (via bivalent scFv-Fc format) is sufficient to trigger clathrin- and dynamin-dependent endocytosis of FGFR1. Monovalent antibody fragments bind but are not internalized. Receptor tyrosine kinase activity is dispensable for this dimerization-induced endocytosis. Antibody fragment internalization assay (bivalent vs. monovalent formats), pharmacological inhibition of clathrin/dynamin pathways, kinase-dead receptor expression Scientific reports Medium 28769084
2020 FGFR1 clustering into larger oligomers via tetravalent antibody stimulates fast, highly efficient receptor internalization via both clathrin-mediated endocytosis and a dynamin-dependent clathrin-independent route, whereas bivalent antibody triggers only clathrin-mediated endocytosis. All endocytic pathways engaged are kinase-independent. Engineered antibodies of different valency, live cell internalization assays, pharmacological inhibition of endocytic routes, kinase-dead FGFR1 expression Molecular oncology Medium 32511887
2022 FGFR1 is SUMOylated at conserved lysines in endothelial cells in response to hypoxia/proangiogenic stimuli; SENP1 acts as the deSUMOylase. SUMOylation restricts FGFR1 tyrosine kinase activation by modulating FGFR1 dimerization and its interaction with phosphatase PTPRG. SUMOylated FGFR1 facilitates FRS2α recruitment to VEGFR2 instead, thereby switching from FGF/FGFR1 to VEGFA/VEGFR2 signaling. SUMOylation-defective FGFR1 mutant knockin mice show reduced angiogenesis in vivo. SUMOylation site mutagenesis, SENP1 knockdown/overexpression, FGFR1 dimerization assay, PTPRG binding assay, FRS2α recruitment assay, endothelial-specific knockin mouse model, in vivo angiogenesis assay Proceedings of the National Academy of Sciences of the United States of America High 35733256
2018 FGFR1 activation by FGF2 promotes EMT, proliferation, migration, and invasion in FGFR1-amplified lung cancer via the FGFR1-ERK1/2-SOX2 axis: FGFR1 activates ERK1/2, which upregulates SOX2, and SOX2 drives EMT and metastatic processes. SOX2 silencing abolishes FGFR1-driven phenotypes. FGF2 stimulation, FGFR1 inhibitor (AZD4547), ERK2 constitutively-active construct transfection, SOX2 knockdown stable cell lines, in vivo orthotopic and subcutaneous xenograft models Oncogene High 29858603
2019 Nuclear FGFR1 occupies transcription start sites in ER+ breast cancer cells, interacts with phosphorylated RNA Polymerase II and FOXA1 (identified by mass spectrometry), and requires FOXA1 for chromatin recruitment. Nuclear FGFR1-driven gene transcription promotes resistance to estrogen suppression and fulvestrant. FGFR tyrosine kinase inhibitor (erdafitinib) does not impair nuclear FGFR1 translocation or genomic activity. ChIP-seq, RNA-seq, mass spectrometry of nuclear FGFR1 interactome, FOXA1 siRNA knockdown, FGFR1(SP-)(NLS) overexpression, in vivo xenograft model Clinical cancer research High 34011560
2020 Opening of Piezo1 mechanosensitive channel in mature adipocytes causes release of FGF1, which induces preadipocyte differentiation through activation of FGFR1. Adipocyte-specific Piezo1 knockout mice show defective preadipocyte differentiation under high-fat diet, identifying an FGF1/FGFR1-mediated feed-back mechanism for adipogenesis. Conditional adipocyte-specific Piezo1 knockout mice, FGF1 secretion measurement, FGFR1 activation assay, preadipocyte differentiation assay, high-fat diet model Nature communications High 32385276
2015 Cadherin-2 (Cdh2) physically associates with and stabilizes FGFR1 protein in mouse epiblast stem cells, as shown by co-immunoprecipitation and Western blot. Cdh2 knockdown reduces FGFR1 protein levels and impairs FGF signaling-dependent pluripotency maintenance; Cdh1 overexpression cannot substitute. Co-immunoprecipitation, Western blot, siRNA knockdown, Cdh2 overexpression in mESCs with FGF2 supplementation Scientific reports Medium 26420260
2017 Distinct Requirements for FGFR1 vs FGFR2 in primitive endoderm development: fluorescent reporter knockins show Fgfr1 is expressed in all blastocyst cell populations while Fgfr2 becomes restricted to extraembryonic lineages. Loss of both receptors prevents primitive endoderm formation; FGFR1 plays a more prominent role than FGFR2. FGFR1 also has a greater influence than FGFR2 in embryonic stem cell exit from pluripotency. Fluorescent reporter knockin lines, conditional double knockout mice, embryonic stem cell differentiation assay Developmental cell High 28552557
2005 Fgfr1 (but not Fgfr3) is essential in the cerebrum for establishing all three commissural axon tracts (corpus callosum, hippocampal commissure, anterior commissure) and for generating telencephalic midline structures including septal cells and three specialized glial types (indusium griseum glia, midline zipper glia, glial wedge). In Fgfr1 heterozygotes with normal midline patterning, commissural defects still occur, indicating at least two distinct FGF-dependent mechanisms. Conditional Fgfr1 knockout mice (brain-specific), histological analysis, axon tracing, comparison with Fgfr3 knockout Developmental biology High 16309667
2001 FGFR1 is phosphorylated in the retina within 15 minutes of retinal detachment, and ERK is activated in Müller and RPE cells; these are among the earliest signaling responses to retinal detachment, preceding morphological changes, suggesting FGF-2 initiates these responses through FGFR1. Western blotting, immunoprecipitation, immunohistochemistry, in situ hybridization on cat and rabbit retina after experimental retinal detachment Investigative ophthalmology & visual science Medium 11328752
2016 FGFR1 promotes glioblastoma radioresistance through PLCγ (PLCG1) as an essential mediator: silencing FGFR1 or inhibiting PLCγ both decrease radioresistance and induce radiation-induced centrosome overduplication and mitotic cell death. FGFR1 silencing also reduces HIF1α expression, which independently contributes to radioresistance. FGFR1 shRNA knockdown, PLCγ inhibition, xenograft mouse models with irradiation, HIF1α expression analysis Cancer research Medium 26896280
2019 Membrane-associated FGFR1 kinase (but not cytoplasmic or nuclear FGFR1 kinase) induces neuronal differentiation in PC12 cells, primarily through ERK activation (pERK and pPLCγ1 elevated; pAKT not altered). Optogenetic activation of cytoplasmic FGFR1 enhances ERK signaling in HEK293 but not PC12 cells. Nuclear FGFR1 activation produces no signaling changes or neurite outgrowth. Optogenetic stimulation of subcellularly targeted FGFR1 (LOV domain fusions directed to membrane, cytoplasm, nucleus), Western blot for pERK/pPLCγ1/pAKT, neurite outgrowth quantification Cells Medium 30875802
2019 Catalytically inactive receptor PTK7 colocalizes with and physically binds FGFR1 via its extracellular domain. PTK7 knockdown reduces ligand-free and FGF-induced FGFR1 phosphorylation, impairs signaling adaptor protein interaction with FGFR1, and reduces downstream signaling activation as well as FGF-induced oncogenic phenotypes (proliferation, colony formation, migration, invasion) in esophageal squamous cell carcinoma cells. Co-immunoprecipitation, co-localization (colocalization assay), PTK7 siRNA knockdown, phosphorylation Western blot, oncogenic phenotype assays FASEB journal Medium 31490704
2022 Gremlin1 binds directly to FGFR1 and activates downstream MAPK signaling to promote prostate cancer lineage plasticity and castration resistance. Gremlin1 interacts with FGFR1 at a different binding interface than the canonical FGF1 ligand, as shown by protein structure docking and mutagenesis. Co-immunoprecipitation, protein structure docking, mutagenesis, MAPK signaling assays, in vivo mouse model with anti-Gremlin1 antibody + ADT Nature cancer High 35624341
2011 A missense mutation in the FGFR1 kinase domain (W691R, hush puppy mouse) abolishes both the IP3/calcium pathway and Ras/MAP kinase pathway activation while the mutant receptor is expressed at the cell membrane normally. The mutant protein appears to exert a dominant negative effect, likely by dimerizing with wild-type receptor. Intracellular calcium measurement (IP3 pathway), MAP kinase pathway activation assay, immunocytochemistry for receptor localization, RT-PCR, heterozygous mouse phenotyping Mammalian genome Medium 21479780
2017 FGFR1 inhibition in FGFR1-amplified lung cancer induces autophagy through the ERK/MAPK pathway (not AKT pathway), accompanied by upregulation of beclin-1. Constitutively active MEK1 or beclin-1 knockdown attenuates FGFR1 inhibition-induced autophagy. Combined FGFR1 inhibition and autophagy inhibition enhances apoptosis. Western blot for LC3/beclin-1, GFP-LC3 puncta assay, MDC staining, constitutively active MEK1 transfection, beclin-1 RNAi, FGFR1 shRNA, pharmacological FGFR1 inhibition (AZD4547) Journal of experimental & clinical cancer research Medium 28558758
2018 The gatekeeper mutation V561M in FGFR1 confers resistance to AZD4547 through increased STAT3 activation downstream of V561M FGFR1. STAT3 knockdown via shRNA restores AZD4547 sensitivity in cells expressing V561M FGFR1. V561M also biases cells toward a mesenchymal phenotype with increased proliferation and invasion. In vitro kinase binding assays, cell-based resistance characterization, CyTOF single-cell analysis, shRNA STAT3 knockdown, pharmacological rescue Molecular cancer research Medium 30257990
2017 FOXC1 transcription factor binds an upstream regulatory region of Fgfr1 (confirmed by ChIP) and activates an Fgfr1 promoter element to induce expression of the FGFR1-IIIc isoform following TGFβ1-induced EMT. FOXC1 knockdown impairs FGF2-mediated 3D cell migration, which is rescued by FGFR1 re-expression. ChIP, luciferase reporter assay, RNA-seq, Foxc1 knockdown/overexpression, 3D migration assay with FGFR1 rescue Molecular cancer research Medium 28684636
2023 VEGF-B binds directly to FGFR1, induces FGFR1/VEGFR1 heterodimer complex formation, and suppresses FGF2-induced ERK activation, thereby inhibiting FGF2/FGFR1-driven angiogenesis and tumor growth. Direct binding assay, co-immunoprecipitation for FGFR1/VEGFR1 complex, ERK activation Western blot, in vitro angiogenesis assays, in vivo tumor models Signal transduction and targeted therapy Medium 37591843
2019 FGFR1 regulates VEGF secretion from breast cancer cells in a MAPK-dependent manner and induces autocrine activation of the VEGF-VEGFR1-AKT pathway to further amplify VEGF secretion. FGFR1 knockout inhibits tumor angiogenesis in vivo. Dual FGFR1/VEGFR1 inhibition shows synergistic anti-angiogenic effects. FGFR1 knockout (in vivo), VEGF secretion assay, MEK inhibitor, FGFR inhibitor (BGJ398), in vivo tumor angiogenesis assay, combination drug treatment Oncogene Medium 29970903
2014 Recombinant thrombomodulin domain rTMD23 physically interacts with FGFR1 (co-precipitated with syndecan-4 from endothelial cells and FGFR1-expressing HEK293 cells; binding kinetics measured by surface plasmon resonance). rTMD23 activates FGFR1 and promotes angiogenesis; FGFR1-specific inhibition (PD173074) or FGFR1 siRNA knockdown blocks rTMD23-induced FGFR1 activation and tube formation. Co-precipitation (Sepharose pulldown), surface plasmon resonance, FGFR1 siRNA knockdown, pharmacological inhibition, in vitro angiogenesis assay, ischemic rat hindlimb model Cardiovascular research Medium 25388665
2013 FGFR1 is essential for prostate cancer progression and metastasis: conditional deletion of fgfr1 in prostate cells (ARR2PBi-Cre/TRAMP/fgfr1loxP/loxP) produces smaller tumors with well-differentiated foci, while tumors escaping deletion retain fgfr1 and exhibit poorly differentiated phenotype. All metastases were primarily negative for the fgfr1 null allele and showed high FGFR1 expression with a neuroendocrine phenotype. Tissue-specific conditional knockout (Cre/lox), histological analysis, allele-specific PCR, FGFR1 IHC, survival analysis Cancer research Medium 23576558
2023 Conditional deletion of endothelial FGFR1 upregulates ROCK2 activity, leading to increased inflammatory cell adhesion and vascular permeability in ALI/ARDS. FGFR1 knockdown in HUVECs activates ROCK2 and promotes endothelial dysfunction. ROCK2-selective inhibition rescues the FGFR1-deficiency phenotype, placing ROCK2 downstream of endothelial FGFR1. Endothelial-specific conditional Fgfr1 knockout (in vivo LPS-ALI model), FGFR1 siRNA knockdown in HUVECs, ROCK2 activity assay, AAV-shROCK2 and pharmacological ROCK2 inhibitor (TDI01) rescue Frontiers in immunology Medium 36969192
2017 A dominant negative FGFR1 mutation (p.W289X) identified in a Kallmann syndrome patient produces a truncated receptor lacking transmembrane and intracellular domains that is secreted into culture medium. This secreted truncated FGFR1 interferes with wild-type receptor function to suppress ERK1/2 phosphorylation downstream. Expression of truncated receptor in culture, Western blot for secreted protein, ERK1/2 phosphorylation assay with co-expression of wild-type and mutant receptor Gene Medium 28411082
2013 X-ray crystallography of FGFR1 tyrosine kinase domain with pyrazolylaminopyrimidine inhibitors reveals that close structural analogs adopt divergent binding modes involving different conformational changes in both the protein and the ligand (including bound water network differences), rationalizing differences in inhibitory potency. X-ray crystallography, isothermal titration calorimetry, surface plasmon resonance ACS medicinal chemistry letters High 24900792
2019 YAP1 upregulates FGFR1 expression via the TEAD binding site on the FGFR1 promoter; conversely, bFGF/FGFR1 signaling induces YAP1 expression via LATS1, forming a reciprocal regulatory loop. Absence of YAP1 abolishes self-renewal ability in FGFR1-amplified lung cancer cells. Promoter TEAD binding site analysis, YAP1 knockdown/overexpression, real-time PCR, Western blot, IHC, orthotopic mouse model Cancer letters Low 29452146
2012 Combined Fgfr1/Fgfr2 double knockout (hGFAP-Cre) in mice reduces cerebellar size due to reduced proliferation of radial glia and glial precursors, impaired granule cell precursor amplification in the external granular layer, and arrested inward migration of granule cells and outward migration of GABA interneurons. These defects disrupt cerebellar laminar architecture and cause impaired motor coordination. Conditional double knockout mice (hGFAP-Cre;Fgfr1flox/flox;Fgfr2flox/flox), histological analysis, BrdU proliferation assay, cell migration analysis, behavioral motor testing Brain research Medium 22578469

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 Frequent and focal FGFR1 amplification associates with therapeutically tractable FGFR1 dependency in squamous cell lung cancer. Science translational medicine 675 21160078
2013 Recurrent somatic alterations of FGFR1 and NTRK2 in pilocytic astrocytoma. Nature genetics 649 23817572
2000 Transformation and Stat activation by derivatives of FGFR1, FGFR3, and FGFR4. Oncogene 222 10918587
1995 Mutations in FGFR1 and FGFR2 cause familial and sporadic Pfeiffer syndrome. Human molecular genetics 203 7795583
2016 FGFR1 and NTRK3 actionable alterations in "Wild-Type" gastrointestinal stromal tumors. Journal of translational medicine 185 27974047
2012 Differential specificity of endocrine FGF19 and FGF21 to FGFR1 and FGFR4 in complex with KLB. PloS one 154 22442730
2016 Germline and somatic FGFR1 abnormalities in dysembryoplastic neuroepithelial tumors. Acta neuropathologica 150 26920151
2017 Distinct Requirements for FGFR1 and FGFR2 in Primitive Endoderm Development and Exit from Pluripotency. Developmental cell 144 28552557
2018 FGFR1-ERK1/2-SOX2 axis promotes cell proliferation, epithelial-mesenchymal transition, and metastasis in FGFR1-amplified lung cancer. Oncogene 139 29858603
2020 Adipocyte Piezo1 mediates obesogenic adipogenesis through the FGF1/FGFR1 signaling pathway in mice. Nature communications 126 32385276
2001 FGFR1, signaling, and AP-1 expression after retinal detachment: reactive Müller and RPE cells. Investigative ophthalmology & visual science 125 11328752
2008 The complex genetics of Kallmann syndrome: KAL1, FGFR1, FGF8, PROKR2, PROK2, et al. Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation 118 18987492
2000 Expression of FGFR1, FGFR2 and FGFR3 during early neural development in the chick embryo. Mechanisms of development 108 10585567
2012 FGFR1 cleavage and nuclear translocation regulates breast cancer cell behavior. The Journal of cell biology 96 22665522
2014 Osteocyte-specific deletion of Fgfr1 suppresses FGF23. PloS one 95 25089825
2013 FGFR1 is essential for prostate cancer progression and metastasis. Cancer research 90 23576558
2000 The FGFR1 inhibitor PD 173074 selectively and potently antagonizes FGF-2 neurotrophic and neurotropic effects. Journal of neurochemistry 86 10987832
2011 Nedd4-1 binds and ubiquitylates activated FGFR1 to control its endocytosis and function. The EMBO journal 73 21765395
2005 Development of midline cell types and commissural axon tracts requires Fgfr1 in the cerebrum. Developmental biology 64 16309667
2018 FGFR1 actionable mutations, molecular specificities, and outcome of adult midline gliomas. Neurology 59 29728520
2021 Nuclear FGFR1 Regulates Gene Transcription and Promotes Antiestrogen Resistance in ER+ Breast Cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 58 34011560
2018 The Hippo/YAP1 pathway interacts with FGFR1 signaling to maintain stemness in lung cancer. Cancer letters 58 29452146
2022 FGFR1 SUMOylation coordinates endothelial angiogenic signaling in angiogenesis. Proceedings of the National Academy of Sciences of the United States of America 57 35733256
2017 Myeloid/lymphoid neoplasms with FGFR1 rearrangement. Leukemia & lymphoma 56 29119847
2023 VEGF-B prevents excessive angiogenesis by inhibiting FGF2/FGFR1 pathway. Signal transduction and targeted therapy 55 37591843
1996 Expression and regulation of Cek-8, a cell to cell signalling receptor in developing chick limb buds. Development (Cambridge, England) 55 8620841
2019 FGFR1 Cooperates with EGFR in Lung Cancer Oncogenesis, and Their Combined Inhibition Shows Improved Efficacy. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 54 30639621
2022 Gremlin1 is a therapeutically targetable FGFR1 ligand that regulates lineage plasticity and castration resistance in prostate cancer. Nature cancer 52 35624341
2012 FGFR1 expression and gene copy numbers in human lung cancer. Virchows Archiv : an international journal of pathology 52 22648708
2017 FGF2/FGFR1 regulates autophagy in FGFR1-amplified non-small cell lung cancer cells. Journal of experimental & clinical cancer research : CR 50 28558758
2013 Myeloid neoplasms associated with eosinophilia and rearrangement of PDGFRA, PDGFRB, and FGFR1: a review. International journal of laboratory hematology 50 23489324
2016 FGFR1 Induces Glioblastoma Radioresistance through the PLCγ/Hif1α Pathway. Cancer research 49 26896280
2017 Mechanisms of Primary Drug Resistance in FGFR1-Amplified Lung Cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 48 28630215
2020 FGFR1 Oncogenic Activation Reveals an Alternative Cell of Origin of SCLC in Rb1/p53 Mice. Cell reports 46 32187553
1995 Developmental expression of fibroblast growth factor receptor-1 (cek-1; flg) during heart development. Developmental dynamics : an official publication of the American Association of Anatomists 46 7734730
2019 Reciprocal regulatory mechanism between miR-214-3p and FGFR1 in FGFR1-amplified lung cancer. Oncogenesis 45 31492847
2018 The FGFR1 V561M Gatekeeper Mutation Drives AZD4547 Resistance through STAT3 Activation and EMT. Molecular cancer research : MCR 42 30257990
2017 Differential regulation of renal Klotho and FGFR1 in normal and uremic rats. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 41 28515153
2017 Design, synthesis and evaluate of novel dual FGFR1 and HDAC inhibitors bearing an indazole scaffold. Bioorganic & medicinal chemistry 41 29317150
2015 Hematolymphoid neoplasms associated with rearrangements of PDGFRA, PDGFRB, and FGFR1. American journal of clinical pathology 41 26276769
2008 Molecular drug targets in myeloproliferative neoplasms: mutant ABL1, JAK2, MPL, KIT, PDGFRA, PDGFRB and FGFR1. Journal of cellular and molecular medicine 41 19175693
2020 FGFR1 regulates proliferation and metastasis by targeting CCND1 in FGFR1 amplified lung cancer. Cell adhesion & migration 37 32380883
2015 FGFR1 inhibition in lung squamous cell carcinoma: questions and controversies. Cell death discovery 37 27551478
2018 Clinical outcomes of myeloid/lymphoid neoplasms with fibroblast growth factor receptor-1 (FGFR1) rearrangement. Hematology (Amsterdam, Netherlands) 35 29486661
2020 Oxysophocarpine suppresses FGFR1-overexpressed hepatocellular carcinoma growth and sensitizes the therapeutic effect of lenvatinib. Life sciences 34 33148422
1996 Expression of FGF1 and FGFR1 in human melanoma tissues. Melanoma research 34 8819125
2021 Fisetin attenuates periodontitis through FGFR1/TLR4/NLRP3 inflammasome pathway. International immunopharmacology 33 33725636
2018 Synergistic anti-angiogenic treatment effects by dual FGFR1 and VEGFR1 inhibition in FGFR1-amplified breast cancer. Oncogene 33 29970903
2014 mTORC1 and FGFR1 signaling in fibrolamellar hepatocellular carcinoma. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 33 24925055
2010 FGFR1 mutations in Kallmann syndrome. Frontiers of hormone research 33 20389085
2023 Role and Therapeutic Potential for Targeting Fibroblast Growth Factor 10/FGFR1 in Relapsed Rheumatoid Arthritis. Arthritis & rheumatology (Hoboken, N.J.) 31 37584284
2022 Multi-organ FGF21-FGFR1 signaling in metabolic health and disease. Frontiers in cardiovascular medicine 27 35983184
2019 Novel TG-FGFR1 and TRIM33-NTRK1 transcript fusions in papillary thyroid carcinoma. Genes, chromosomes & cancer 27 30664823
2019 Effects of FGF2/FGFR1 Pathway on Expression of A1 Astrocytes After Infrasound Exposure. Frontiers in neuroscience 27 31130839
2017 Antibody-induced dimerization of FGFR1 promotes receptor endocytosis independently of its kinase activity. Scientific reports 27 28769084
2014 FGFR1 mediates recombinant thrombomodulin domain-induced angiogenesis. Cardiovascular research 27 25388665
2019 Intrinsic FGFR2 and Ectopic FGFR1 Signaling in the Prostate and Prostate Cancer. Frontiers in genetics 25 30761180
2010 Decreased expression of FGFR1, SOS1, RAF1 genes in cryptorchidism. Urologia internationalis 25 20389169
2017 FOXC1 Regulates FGFR1 Isoform Switching to Promote Invasion Following TGFβ-Induced EMT. Molecular cancer research : MCR 24 28684636
2012 Impaired motor coordination and disrupted cerebellar architecture in Fgfr1 and Fgfr2 double knockout mice. Brain research 24 22578469
2019 Tie2-FGFR1 Interaction Induces Adaptive PI3K Inhibitor Resistance by Upregulating Aurora A/PLK1/CDK1 Signaling in Glioblastoma. Cancer research 23 31416846
2018 miRNA-133b targets FGFR1 and presents multiple tumor suppressor activities in osteosarcoma. Cancer cell international 23 30574019
2013 FGFR1 amplifications in squamous cell carcinomas of the lung: diagnostic and therapeutic implications. Translational lung cancer research 23 25806220
2021 Synergistic effects of FGFR1 and PLK1 inhibitors target a metabolic liability in KRAS-mutant cancer. EMBO molecular medicine 22 34369083
2020 FGFR1 clustering with engineered tetravalent antibody improves the efficiency and modifies the mechanism of receptor internalization. Molecular oncology 22 32511887
2002 FGFR1 expression and FGFR1-FGF-2 colocalisation in rat retina: sites of FGF-2 action on rat photoreceptors. Growth factors (Chur, Switzerland) 22 12708794
2018 Activating FGFR1 Mutations in Sporadic Pheochromocytomas. World journal of surgery 21 29159601
2013 FGFR1 and FGFR2 mutations in Pfeiffer syndrome. The Journal of craniofacial surgery 21 23348274
2022 FGFR1 is a potential therapeutic target in neuroblastoma. Cancer cell international 20 35488346
2010 Construction of recombinant FGFR1 containing full-length gene and its potential application. Plasmid 20 20434485
2024 Dihydroartemisinin inhibited vasculogenic mimicry in gastric cancer through the FGF2/FGFR1 signaling pathway. Phytomedicine : international journal of phytotherapy and phytopharmacology 19 39214017
2020 MiR-3116 sensitizes glioma cells to temozolomide by targeting FGFR1 and regulating the FGFR1/PI3K/AKT pathway. Journal of cellular and molecular medicine 19 32181582
2018 FGFR1 expression defines clinically distinct subtypes in pancreatic cancer. Journal of translational medicine 19 30593273
2017 Resistance mediated by alternative receptor tyrosine kinases in FGFR1-amplified lung cancer. Carcinogenesis 19 28968756
2015 Novel FGFR1 and KISS1R Mutations in Chinese Kallmann Syndrome Males with Cleft Lip/Palate. BioMed research international 19 26199944
2024 Pharmacological and Biological Targeting of FGFR1 in Cancer. Current issues in molecular biology 18 39590377
2020 circITGA7 Functions as an Oncogene by Sponging miR-198 and Upregulating FGFR1 Expression in Thyroid Cancer. BioMed research international 18 32685526
2015 Cdh2 stabilizes FGFR1 and contributes to primed-state pluripotency in mouse epiblast stem cells. Scientific reports 18 26420260
2020 Peripheral FGFR1 Regulates Myofascial Pain in Rats via the PI3K/AKT Pathway. Neuroscience 17 32278061
2019 Membrane-Associated, Not Cytoplasmic or Nuclear, FGFR1 Induces Neuronal Differentiation. Cells 17 30875802
2015 The impact of FGFR1 and FRS2α expression on sorafenib treatment in metastatic renal cell carcinoma. BMC cancer 17 25900027
2015 Fibroblast growth factor receptor 1 (FGFR1) expression in phosphaturic mesenchymal tumors. International journal of clinical and experimental pathology 17 26464698
2024 Gentiopicroside ameliorates glucose and lipid metabolism in T2DM via targeting FGFR1. Phytomedicine : international journal of phytotherapy and phytopharmacology 16 38885580
2023 Deficiency of endothelial FGFR1 signaling via upregulation of ROCK2 activity aggravated ALI/ARDS. Frontiers in immunology 16 36969192
2019 Actionable FGFR1 and BRAF mutations in adult circumscribed gliomas. Journal of neuro-oncology 16 31673897
2017 A dominant negative FGFR1 mutation identified in a Kallmann syndrome patient. Gene 16 28411082
2011 A missense mutation in Fgfr1 causes ear and skull defects in hush puppy mice. Mammalian genome : official journal of the International Mammalian Genome Society 16 21479780
2024 FGFR1 fusions as a novel molecular driver in rhabdomyosarcoma. Genes, chromosomes & cancer 15 38607246
2023 FGF21/FGFR1-β-KL cascade in cardiomyocytes modulates angiogenesis and inflammation under metabolic stress. Heliyon 15 37123894
2019 Catalytically inactive receptor tyrosine kinase PTK7 activates FGFR1 independent of FGF. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 15 31490704
2023 The FGFR1 Signaling Pathway Upregulates the Oncogenic Transcription Factor FOXQ1 to Promote Breast Cancer Cell Growth. International journal of biological sciences 14 36778115
2022 Rosette-forming glioneuronal tumours are midline, FGFR1-mutated tumours. Neuropathology and applied neurobiology 14 35293634
2021 Intrinsically Fluorescent Oligomeric Cytotoxic Conjugates Toxic for FGFR1-Overproducing Cancers. Biomacromolecules 14 34855396
2016 Amplification of FGFR1 gene and expression of FGFR1 protein is found in different histological types of lung carcinoma. Virchows Archiv : an international journal of pathology 14 27194548
2013 FGFR1 Kinase Inhibitors: Close Regioisomers Adopt Divergent Binding Modes and Display Distinct Biophysical Signatures. ACS medicinal chemistry letters 14 24900792
2013 Copy number gains of FGFR1 and 3q chromosome in squamous cell carcinoma of the lung. Translational lung cancer research 14 25806221
2023 FGF2 drives osteosarcoma metastasis through activating FGFR1-4 receptor pathway-mediated ICAM-1 expression. Biochemical pharmacology 13 37832794
2020 Temporospatial Expression of Fgfr1 and 2 During Lung Development, Homeostasis, and Regeneration. Frontiers in pharmacology 13 32194398
2020 The Relationship between Leptin, the Leptin Receptor and FGFR1 in Primary Human Breast Tumors. Cells 13 33019728
2014 NCAM and FGFR1 coexpression and colocalization in renal tumors. International journal of clinical and experimental pathology 13 24817936

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