Affinage

FOLR1

Folate receptor alpha · UniProt P15328

Length
257 aa
Mass
29.8 kDa
Annotated
2026-06-09
100 papers in source corpus 26 papers cited in narrative 26 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

FOLR1 (FRα) is a high-affinity, GPI-anchored cell-surface receptor that mediates receptor-mediated import of 5-methyltetrahydrofolate, functioning as the principal folate-uptake entity in epithelial and barrier tissues (PMID:20619709, PMID:25816016). Its transport activity follows saturation kinetics, is sensitive to reactive oxygen species, and is abolished by GPI cleavage or silencing, confirming FOLR1 itself as the transporting moiety (PMID:20619709). FOLR1-dependent folate delivery is required for normal development: knockout mouse embryos display cardiovascular and cardiac neural crest defects rescuable by folinic acid (PMID:17286298), FRα marks midbrain dopaminergic progenitors (PMID:27580818), and FOLR1 cooperates genetically with Shroom3 to drive Src-kinase/MLCK-dependent apical constriction during neural tube closure (PMID:30670450). In humans, a loss-of-function p.Cys105Arg mutation disrupts a folding-critical disulfide bond, causing cerebral folate deficiency and establishing FOLR1 as the folate transporter of the choroid plexus blood–CSF barrier (PMID:20857335). Surface abundance is set post-translationally by mTORC1/mTORC2 signaling and by FUT8-mediated core-fucosylation at Asn-201, both of which tune folate-uptake capacity (PMID:27562465, PMID:34093861), while transcription is controlled by CIC/capicua and by YAP1–TEAD2 (PMID:32820034, PMID:37269960). Beyond folate import, FOLR1 engages non-canonical signaling: ligand-bound FRα activates c-SRC/ERK1/2/NF-κB/TP53 to enforce cell-cycle arrest in colon cancer (PMID:26056802), an ERK1/2/TSLC1 axis in nasopharyngeal cancer (PMID:29070520), and an EGFR/AKT/GSK-3β axis that stabilizes β-catenin to promote proliferation and migration (PMID:37702010); it can also translocate to the nucleus, where NSD2/H3K36me2 recruits it to glycolytic gene promoters to act as a transcriptional driver of aerobic glycolysis (PMID:39798773). These activities underlie FOLR1's role in tumor folate uptake, proliferation, invasion, and drug resistance, making it a validated target for anti-FRα antibodies and antibody-drug conjugates whose efficacy tracks with surface receptor density (PMID:23144806, PMID:25816016, PMID:25904506).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1994 Medium

    Establishing which folate receptor isoform is expressed in placental trophoblast resolved that FRα (FOLR1), not FRβ, is the relevant transporter in this tissue, anchoring later transport and developmental work to the correct gene product.

    Evidence Isoform-specific RT-PCR, Northern blot, and sequencing in placental trophoblast and JAR cells

    PMID:8061055

    Open questions at the time
    • No functional transport assay in this study
    • Does not address regulation or signaling roles
  2. 2007 High

    Folr1 knockout in mouse and transcriptomic profiling showed that FOLR1-mediated folate transport is required for cardiac neural crest migration and cardiovascular morphogenesis, framing FOLR1 as a developmental folate-delivery gene rather than a passive carrier.

    Evidence Folr1 knockout mouse embryos with folinic acid rescue and microarray/qPCR of cardiac tissue

    PMID:17286298 PMID:18028541

    Open questions at the time
    • Mechanism linking folate to neural crest gene programs not resolved at protein level
    • Whether effects are purely metabolic or also signaling
  3. 2010 Medium

    Human loss-of-function genetics and in vitro kinetic analysis established FOLR1 as the high-affinity folate transporter at the blood–CSF barrier and demonstrated saturable receptor-mediated uptake sensitive to oxidative stress.

    Evidence Patient FOLR1 sequencing with CSF 5-MTHF measurement; KB-cell uptake assays with PIPLC cleavage and siRNA

    PMID:20619709 PMID:20857335

    Open questions at the time
    • No in vitro reconstitution of transport
    • Single family for the disease mutation
    • Cycling/endocytic mechanism of uptake not detailed
  4. 2011 Medium

    Folr1-null fibroblasts linked FOLR1 loss to altered TGFβ/Smad and Wnt signaling, indicating folate status feeds into developmental signaling pathways relevant to neural tube closure.

    Evidence Primary Folr1-/- MEF reporter assays and Wnt target gene expression

    PMID:21649587

    Open questions at the time
    • Direct molecular link between FOLR1 and these pathways not established
    • Single lab, reporter-based readouts
  5. 2012 Medium

    Bidirectional manipulation in ovarian cancer cells defined FOLR1 as a pro-tumorigenic driver of folate-dependent proliferation, migration, and invasion counterbalanced by RFC, moving FOLR1 from a transporter to a phenotype-controlling oncology target.

    Evidence Stable FRα knockdown, RFC overexpression, migration/invasion assays, E-cadherin Western blot

    PMID:23144806

    Open questions at the time
    • Signaling intermediaries not identified
    • Single lab
  6. 2013 Medium

    Computational modeling and antibody studies began defining the folate-binding pocket and validated FOLR1 surface expression as an immunotherapy/ADCC target.

    Evidence Homology modeling/MD/docking; farletuzumab ADCC and ovarian xenograft assays

    PMID:23880302 PMID:24025360

    Open questions at the time
    • Structural model lacks experimental validation
    • ADCC mechanism shown without crystallographic epitope mapping
  7. 2015 Medium

    A series of studies linked FOLR1 surface level directly to folate import, proliferation under low folate, and sensitivity to FRα-targeted ADCs, while defining a folate-bound FRα/c-SRC/ERK/NF-κB/TP53 cascade controlling cell cycle.

    Evidence FOLR1 KD/OE in TNBC, ADC cytotoxicity/bystander/xenograft assays, and siRNA epistasis with signaling Western blots in colon cancer

    PMID:25816016 PMID:25904506 PMID:26056802

    Open questions at the time
    • Direct physical coupling of FRα to c-SRC not demonstrated
    • Context-dependence of pro- vs anti-proliferative signaling unresolved
  8. 2015 High

    QTL mapping and transgenic rescue in SHR rats established renal FOLR1-mediated folate reabsorption as a determinant of sulfur amino acid metabolism and metabolic syndrome traits.

    Evidence Congenic strains, promoter reporter assay, Folr1 transgenic rescue, metabolic phenotyping

    PMID:26667416

    Open questions at the time
    • Causal promoter variant mechanism in human metabolic disease not addressed
    • Tissue-specific contributions not dissected
  9. 2016 Medium

    Identification of mTORC1/mTORC2 as post-translational regulators of FRα plasma-membrane abundance, and prospective FolR1+ isolation of dopaminergic progenitors, expanded FOLR1 regulation and lineage-marker roles.

    Evidence raptor/rictor siRNA with membrane fractionation in trophoblasts; FACS/MACS sorting and differentiation of FolR1+ neural progenitors

    PMID:27562465 PMID:27580818

    Open questions at the time
    • Trafficking machinery downstream of mTOR not identified
    • Whether FolR1 marking is functional or incidental in dopaminergic lineage unknown
  10. 2017 Medium

    Epistasis dissection defined an FRα/ERK1/2/TSLC1 pathway through which folate-bound FOLR1 suppresses nasopharyngeal cancer cell proliferation and invasion, adding a second tumor-suppressive signaling branch.

    Evidence ERK inhibitor and TSLC1 siRNA with proliferation/invasion/migration assays

    PMID:29070520

    Open questions at the time
    • Mechanism of FRα-to-MEK/ERK coupling unresolved
    • Single lab
  11. 2019 High

    Multi-system genetics showed FOLR1 cooperates with Shroom3 via a Src-kinase/MLCK/phospho-myosin axis to drive apical constriction, mechanistically connecting folate signaling to morphogenetic cell-shape change and neural tube closure.

    Evidence Cell-culture and chick embryo apical constriction rescue, MLCK/Src inhibitors, Shroom3;Folr1 double-heterozygous mice, phospho-MLC Western blot

    PMID:30670450

    Open questions at the time
    • Direct biochemical link between FRα and MLCK not shown
    • How folate signal reaches the cytoskeleton from a GPI-anchored receptor unclear
  12. 2021 Medium

    FUT8-dependent core-fucosylation at Asn-201, FOLR1-driven sorafenib resistance via autophagy, and folinic acid/Folr1-stimulated β-cell differentiation broadened FOLR1's roles into glycan-regulated uptake, drug resistance, and one-carbon-metabolism-driven regeneration.

    Evidence Glycoproteomics with FUT8 siRNA; IP-MS and autophagy-inhibitor epistasis in HCC; zebrafish/pig islet gain-of-function with metabolomics

    PMID:33677528 PMID:34093861 PMID:34099692

    Open questions at the time
    • FOLR1 autophagy-protein interactors not individually validated
    • Causal metabolite mediators of β-cell regeneration not proven
    • Single labs per finding
  13. 2023 Medium

    FOLR1 was shown to drive an EGFR/AKT/GSK-3β axis stabilizing β-catenin, an APOBEC3B-dependent antiviral effect via induced folate deficiency, and YAP1–TEAD2-controlled expression modulating glioma temozolomide sensitivity, extending its non-canonical signaling and transcriptional regulation.

    Evidence Inhibitor/siRNA epistasis and ubiquitination assays (LSCC); OE/KD with folate rescue and VSV assays; ChIP, verteporfin, and DNA-damage readouts in glioma

    PMID:37028598 PMID:37269960 PMID:37702010

    Open questions at the time
    • Whether β-catenin stabilization is folate-dependent unclear
    • Direct FRα–EGFR coupling not shown
    • Single lab per study
  14. 2025 Medium

    Demonstration that NSD2/H3K36me2 recruits nuclear FOLR1 to glycolytic gene promoters established a moonlighting transcription-factor role driving aerobic glycolysis in pulmonary artery endothelial cells.

    Evidence ChIP for FOLR1 and H3K36me2, promoter activity and metabolic flux assays, NSD2/FOLR1 KD in vitro and monocrotaline PAH mouse model

    PMID:39798773

    Open questions at the time
    • Mechanism and trafficking route of GPI-anchored FOLR1 to the nucleus unexplained
    • Whether nuclear FOLR1 binds DNA directly or via cofactors unknown
    • Single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single GPI-anchored folate receptor mechanistically couples extracellular folate binding to intracellular kinase cascades and to nuclear transcriptional activity, and what determines tumor-suppressive versus pro-tumorigenic signaling outcomes, remains unresolved.
  • No structural basis for FRα-to-cytoplasmic-effector coupling
  • Mechanism of nuclear translocation of a GPI-anchored protein unknown
  • Context-dependence of opposing signaling outputs not explained

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 4 GO:0008289 lipid binding 2 GO:0140110 transcription regulator activity 1
Localization
GO:0005886 plasma membrane 3 GO:0005634 nucleus 1
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-382551 Transport of small molecules 3 R-HSA-1266738 Developmental Biology 2 R-HSA-1430728 Metabolism 2
Partners
CICEGFRFUT8NSD2TEAD2YAP1

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1994 FR-α (FOLR1) is the isoform selectively expressed in human placental syncytiotrophoblast and choriocarcinoma cells, not FR-β as previously believed. RT-PCR with isoform-specific primers and Northern blot analysis of placental trophoblast cells and JAR choriocarcinoma cells confirmed only FR-α mRNA, with nucleotide sequences identical to FR-α cDNA. RT-PCR with isoform-specific primers, Northern blot analysis, DNA sequencing Biochimica et biophysica acta Medium 8061055
1999 DNA vaccination with FRα (FOLR1) cDNA induces both IgG2a antibody responses and cytotoxic T lymphocyte activity against FRα-expressing tumor cells in mice, and delays tumor growth upon challenge with FRα-transduced cells, demonstrating immunogenicity of the surface-expressed protein. In vivo DNA vaccination, FACS-based antibody detection, cytotoxic T lymphocyte assay, tumor challenge model Cancer gene therapy Medium 10419053
2007 Folr1 knockout mouse embryos develop cardiovascular abnormalities including outflow tract defects, aortic arch artery anomalies, and dextracardia, with abnormal heart looping and disrupted migration of cardiac neural crest cells; maternal folinic acid supplementation rescues these defects in a dose-dependent manner, implicating FOLR1-mediated folate transport in cardiac neural crest cell function and pharyngeal arch/secondary heart field signaling. Folr1 knockout mouse model, folinic acid dose-response rescue study, histological analysis of cardiac development Birth defects research. Part A, Clinical and molecular teratology High 17286298
2007 Folr1 gene ablation alters expression of genes involved in cell migration, cytoskeletal organization, cell-cell adhesion, and cellular redox status in developing cardiac and conotruncal tissues, suggesting FOLR1-dependent folate homeostasis regulates gene expression programs required for cardiovascular morphogenesis. Microarray analysis of Folr1 knockout embryo cardiac tissue at three developmental stages, validated by quantitative real-time PCR BMC developmental biology Medium 18028541
2010 Loss-of-function homozygous missense mutation p.Cys105Arg in FOLR1 abolishes a predicted disulfide bond required for correct protein folding, causing defective cerebral folate transport across the blood-CSF barrier and profound CSF 5-methyltetrahydrofolate deficiency, establishing that FOLR1 is the primary folate transporter at the choroid plexus. FOLR1 gene sequencing in patient with cerebral folate deficiency, CSF 5-MTHF measurement by HPLC, structural prediction of disulfide bond disruption Journal of inherited metabolic disease Medium 20857335
2010 FOLR1-dependent 5-methyltetrahydrofolate (MTHF) uptake in KB cells follows saturation kinetics consistent with high-affinity receptor-mediated transport at physiological MTHF concentrations; reactive oxygen species (but not valproate or carbamazepine) significantly decrease FOLR1-mediated MTHF uptake, as confirmed by PIPLC cleavage and siRNA silencing of FOLR1. KB cell culture assay, phosphatidylinositol-specific phospholipase C (PIPLC) cleavage, siRNA knockdown, MTHF uptake quantification Molecular genetics and metabolism High 20619709
2011 Folr1-deficient mouse embryonic fibroblasts show attenuated TGFβ1/Smad signaling (measured by Smad-dependent reporter assay) and increased canonical Wnt pathway activity (Wnt-3a-stimulated Axin2 expression), demonstrating that FOLR1 loss alters developmental signaling pathways relevant to neural tube closure. Primary Folr1-/- mouse embryonic fibroblast cultures, luciferase reporter assay (p3TP-lux), quantitative gene expression analysis of Wnt target genes Cell biology international Medium 21649587
2012 FOLR1 overexpression in ovarian cancer cells promotes folate uptake and enhances cell proliferation, migration, and invasion in response to folate; stable knockdown of FOLR1 blocks folate-induced cancer cell migration and invasion and reverses downregulation of E-cadherin. Ectopic overexpression of RFC (reduced folate carrier) phenocopies FRα knockdown, suggesting RFC counterbalances FRα-mediated pro-tumorigenic signaling. Stable FRα knockdown and RFC overexpression in ovarian cancer cell lines, in vitro proliferation, migration and invasion assays, E-cadherin Western blot PloS one Medium 23144806
2013 Homology modeling and molecular dynamics of FOLR1 using the riboflavin-binding protein crystal structure as template revealed a full disulfide bridge network and identified key residues in the folate-binding pocket; docking studies showed that folic acid and vintafolide share the same binding site, with Trp and His residues contributing to ligand specificity. Homology modeling, molecular dynamics simulation, in silico ligand docking Journal of molecular graphics & modelling Low 23880302
2013 The anti-FOLR1 monoclonal antibody farletuzumab (MORAb-003) mediates its antitumor effect against ovarian cancer xenografts primarily through antibody-dependent cellular cytotoxicity (ADCC), as demonstrated in an experimental ovarian cancer model. ADCC assay, human ovarian cancer xenograft mouse model with farletuzumab treatment Cancer biology & therapy Medium 24025360
2015 FOLR1 knockdown in triple-negative breast cancer cell lines with high endogenous FOLR1 expression causes growth inhibition, while FOLR1 overexpression promotes folate uptake and confers growth advantage under low-folate conditions, directly linking surface FOLR1 expression to folate import and cell proliferation. RNA interference knockdown, FOLR1 overexpression, folate uptake assay, cell proliferation assay in low-folate medium PloS one Medium 25816016
2015 Folic acid (FA) inhibits colon cancer cell proliferation through a FOLR1-dependent signaling cascade: FA binding to FRα activates c-SRC, which activates ERK1/2, leading to NFκB nuclear translocation, TP53 upregulation, and increased CDKN1A/CDKN1B expression causing G0/G1 arrest. Knockdown of FOLR1 abolishes FA-induced c-SRC pathway activation and downstream effects. FRα siRNA knockdown, TP53 siRNA knockdown, Western blot (c-SRC, ERK1/2, NFκB, TP53, CDKN1A, CDKN1B), cell cycle analysis, in vivo xenograft Scientific reports Medium 26056802
2015 FOLR1 surface expression level is a major determinant of sensitivity to anti-FOLR1 antibody-drug conjugate (ADC) IMGN853/mirvetuximab soravtansine; cells with low or no FRα are resistant, while high FRα-expressing cells are highly sensitive, and bystander cytotoxic activity is observed against FRα-negative cells co-cultured with FRα-positive cells. FRα expression quantification by immunohistochemistry, in vitro cytotoxicity assays, FRα-positive and FRα-negative co-culture bystander assay, xenograft models Molecular cancer therapeutics Medium 25904506
2015 Genetic variation in the Folr1 promoter of spontaneously hypertensive rats (SHR) reduces renal Folr1 expression and folate reabsorption, causing decreased serum folate, hypercysteinemia, adiposity, reduced insulin sensitivity, and increased blood pressure; transgenic rescue with a Folr1 transgene in SHR ameliorates these metabolic disturbances, establishing FOLR1-mediated renal folate reabsorption as a regulator of sulfur amino acid metabolism and metabolic syndrome. QTL mapping, SHR.BN-chr.1 congenic strain analysis, luciferase promoter reporter assay, Folr1 transgenic rescue experiment, metabolic phenotyping Hypertension High 26667416
2016 mTORC1 and mTORC2 positively regulate folate uptake in primary human trophoblast cells by controlling the plasma membrane abundance of FR-α (FOLR1) and RFC through post-translational mechanisms, without affecting total protein levels; silencing of raptor (mTORC1) or rictor (mTORC2) markedly decreases surface FR-α and reduces folate uptake; mTORC2 but not mTORC1 mediates insulin+IGF-1-stimulated folate uptake. siRNA silencing of raptor/rictor, plasma membrane fractionation, folate uptake assay in primary human trophoblast cells Scientific reports Medium 27562465
2016 FolR1 specifically marks midbrain dopaminergic (mesDA) neural progenitors and immature dopamine neurons during mouse development (E9.5–E14.5) and in ESC-derived cultures; FACS/MACS-sorted FolR1+ neural progenitors give rise to TH+ and Pitx3+ dopamine neurons, while FolR1-negative cells generate non-dopaminergic neurons and glia. Immunofluorescence co-staining with Lmx1a, FACS/MACS cell sorting, in vitro differentiation assay of sorted populations Scientific reports Medium 27580818
2017 Folic acid (FA) bound to FRα induces MEK/ERK1/2 activation and increases TSLC1 and E-cadherin expression in nasopharyngeal cancer cells; blocking ERK1/2 activation attenuates FA-mediated TSLC1 upregulation; TSLC1 knockdown abolishes FA-mediated inhibition of proliferation, invasion and migration, defining an FRα/ERK1/2/TSLC1 signaling pathway. ERK1/2 inhibitor treatment, siRNA knockdown of TSLC1, Western blot, proliferation/invasion/migration assays Bioscience reports Medium 29070520
2019 Folic acid modifies epithelial cell shape during morphogenesis via FOLR1 and MLCK in a RhoA/ROCK-independent but Src-kinase-dependent manner; co-expression of Folr1 rescues the apical constriction defect of a Rho-kinase-binding mutant of Shroom3 in vitro; treatment with FA is accompanied by elevated phospho-myosin light chain and MLCK; doubly heterozygous mice lacking one copy each of Shroom3 and Folr1 show neural tube defects with reduced activated myosin and MLCK. Epithelial cell culture apical constriction model, chick embryo neural epithelium rescue assay, MLCK inhibitor and Src-kinase inhibitor treatment, double heterozygous mouse genetics, phospho-MLC Western blot Biology open High 30670450
2020 CIC (capicua) transcription factor directly binds to octameric sequences in the FOLR1 promoter; CIC loss-of-function variants (including a nonsense mutation p.R353X) downregulate FOLR1 expression in HeLa cells and patient-derived iPSCs, and decrease cellular folic acid binding, establishing CIC as a transcriptional regulator of FOLR1 expression. Whole exome sequencing, promoter binding assay (CIC ChIP/reporter), siRNA in HeLa cells, iPSC-derived cells from CFD proband, folic acid binding assay Journal of medical genetics High 32820034
2021 Core-fucosylation of FOLR1 (particularly at glycosite Asn-201) positively regulates cellular folate uptake capacity; FUT8 is a driver of HGF/TGF-β1-induced EMT in HCC cells, and FUT8 silencing reduces FOLR1 core-fucosylation and partially blocks EMT. Enhanced folate uptake mediated by core-fucosylated FOLR1 promotes EMT progression. Mass spectrometry-based glycoproteomics, FUT8 siRNA knockdown, intact glycopeptide quantification, molecular biology assays for EMT markers, folate uptake assay Theranostics Medium 34093861
2021 Folr1 overexpression and folinic acid treatment stimulate β-cell differentiation from ductal cells in zebrafish and in neonatal pig islet cultures; comparative metabolomics of zebrafish with/without β-cell ablation and folinic acid treatment implicates pyrimidine, carnitine, and serine pathways as downstream effectors of FOLR1/one-carbon metabolism in β-cell regeneration. Zebrafish genetic screen, folr1 overexpression and folinic acid treatment, neonatal pig islet culture, comparative metabolomics Nature communications Medium 34099692
2021 FOLR1 overexpression drives sorafenib resistance in HCC cells; immunoprecipitation-mass spectrometry identified interaction between FOLR1 and autophagy-related proteins; FOLR1-induced resistance is accompanied by autophagy activation; autophagy inhibition significantly reduces FOLR1-induced drug resistance. Label-free quantitative proteomics, siRNA knockdown, FOLR1 overexpression, immunoprecipitation-mass spectrometry, autophagy inhibitor treatment, cell viability assay Carcinogenesis Medium 33677528
2023 FOLR1 overexpression increases APOBEC3B expression and suppresses VSV viral replication in HeLa cells and in vivo by causing intracellular folate deficiency; the antiviral effect is dependent on folate deficiency rather than direct antiviral signaling, as exogenous folate supplementation reverses FOLR1-mediated viral suppression. FOLR1 overexpression in HeLa cells and mice, VSV infection assay, APOBEC3B knockdown, folate supplementation rescue, in vivo mouse model Virologica Sinica Medium 37028598
2023 FOLR1 promotes proliferation and migration of laryngeal squamous cell carcinoma cells by stabilizing β-catenin through the EGFR/AKT/GSK-3β signaling axis; FOLR1 inhibits β-catenin ubiquitination and degradation; blocking EGFR or the AKT/GSK-3β axis abolishes FOLR1's effects on β-catenin expression and nuclear translocation; β-catenin siRNA knockdown abolishes FOLR1-induced proliferation and migration. siRNA knockdown of FOLR1 and β-catenin, EGFR inhibitor treatment, AKT inhibitor treatment, co-immunoprecipitation/ubiquitination assay, Western blot for β-catenin nuclear localization Molecular carcinogenesis Medium 37702010
2023 YAP1 and its partner transcription factor TEAD2 regulate FOLR1 expression in gliomas; chromatin immunoprecipitation and YAP1-TEAD inhibitor (verteporfin) treatment demonstrated direct transcriptional control; FOLR1 depletion in IDH1 wild-type glioma cells increases sensitivity to temozolomide-mediated cell death and heightens DNA damage markers (γH2AX, ATM phosphorylation). Chromatin immunoprecipitation (ChIP), mutant YAP1 overexpression, verteporfin treatment (YAP1-TEAD inhibitor), FOLR1 siRNA knockdown, γH2AX and pATM assay, cell death assay Cellular signalling Medium 37269960
2025 NSD2-mediated H3K36me2 recruits nuclear FOLR1 to promoters of glycolytic genes (HK2, TIGAR, G6PD) in pulmonary artery endothelial cells; FOLR1 acts as a transcription factor, and its nuclear translocation depends on NSD2 activity; NSD2 or FOLR1 knockdown reduces promoter activity and expression of glycolytic genes, and reverses the metabolic shift toward aerobic glycolysis in monocrotaline-induced PAH. NSD2 and FOLR1 siRNA knockdown, ChIP for H3K36me2 and FOLR1 at glycolytic gene promoters, promoter activity assay, metabolic flux analysis (OCR, ECAR), in vivo monocrotaline PAH mouse model Cellular signalling Medium 39798773

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2023 Mirvetuximab Soravtansine in FRα-Positive, Platinum-Resistant Ovarian Cancer. The New England journal of medicine 340 38055253
2015 IMGN853, a Folate Receptor-α (FRα)-Targeting Antibody-Drug Conjugate, Exhibits Potent Targeted Antitumor Activity against FRα-Expressing Tumors. Molecular cancer therapeutics 187 25904506
2022 Emerging roles for folate receptor FOLR1 in signaling and cancer. Trends in endocrinology and metabolism: TEM 133 35094917
2020 Phase Ib study of mirvetuximab soravtansine, a folate receptor alpha (FRα)-targeting antibody-drug conjugate (ADC), in combination with bevacizumab in patients with platinum-resistant ovarian cancer. Gynecologic oncology 119 32081463
2017 Characterization of folate receptor alpha (FRα) expression in archival tumor and biopsy samples from relapsed epithelial ovarian cancer patients: A phase I expansion study of the FRα-targeting antibody-drug conjugate mirvetuximab soravtansine. Gynecologic oncology 119 28843653
2015 Folate receptor-α (FOLR1) expression and function in triple negative tumors. PloS one 108 25816016
2023 Safety and efficacy of mirvetuximab soravtansine, a folate receptor alpha (FRα)-targeting antibody-drug conjugate (ADC), in combination with bevacizumab in patients with platinum-resistant ovarian cancer. Gynecologic oncology 99 36736157
2023 FDA Approval Summary: Mirvetuximab Soravtansine-Gynx for FRα-Positive, Platinum-Resistant Ovarian Cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 90 37212825
2014 Evidence for a time-dependent association between FOLR1 expression and survival from ovarian carcinoma: implications for clinical testing. An Ovarian Tumour Tissue Analysis consortium study. British journal of cancer 90 25349970
2012 Paradoxical impact of two folate receptors, FRα and RFC, in ovarian cancer: effect on cell proliferation, invasion and clinical outcome. PloS one 89 23144806
2018 Folate receptor 1 (FOLR1) targeted chimeric antigen receptor (CAR) T cells for the treatment of gastric cancer. PloS one 79 29874279
2018 MORAb-202, an Antibody-Drug Conjugate Utilizing Humanized Anti-human FRα Farletuzumab and the Microtubule-targeting Agent Eribulin, has Potent Antitumor Activity. Molecular cancer therapeutics 78 30262588
2018 Safety and activity findings from a phase 1b escalation study of mirvetuximab soravtansine, a folate receptor alpha (FRα)-targeting antibody-drug conjugate (ADC), in combination with carboplatin in patients with platinum-sensitive ovarian cancer. Gynecologic oncology 74 30093227
2013 Folate-receptor 1 (FOLR1) protein is elevated in the serum of ovarian cancer patients. Clinical biochemistry 55 23528302
2009 Expression of the folate receptor genes FOLR1 and FOLR3 differentiates ovarian carcinoma from breast carcinoma and malignant mesothelioma in serous effusions. Human pathology 55 19454358
2021 Tandem CAR-T cells targeting FOLR1 and MSLN enhance the antitumor effects in ovarian cancer. International journal of biological sciences 54 34803504
1994 Selective expression of the high-affinity isoform of the folate receptor (FR-alpha) in the human placental syncytiotrophoblast and choriocarcinoma cells. Biochimica et biophysica acta 52 8061055
2021 Site-specific glycoproteomic analysis revealing increased core-fucosylation on FOLR1 enhances folate uptake capacity of HCC cells to promote EMT. Theranostics 46 34093861
2007 Cardiovascular abnormalities in Folr1 knockout mice and folate rescue. Birth defects research. Part A, Clinical and molecular teratology 46 17286298
2013 The antitumor activity of the human FOLR1-specific monoclonal antibody, farletuzumab, in an ovarian cancer mouse model is mediated by antibody-dependent cellular cytotoxicity. Cancer biology & therapy 44 24025360
2010 Progressive ataxia and myoclonic epilepsy in a patient with a homozygous mutation in the FOLR1 gene. Journal of inherited metabolic disease 44 20857335
2022 CBFA2T3-GLIS2 model of pediatric acute megakaryoblastic leukemia identifies FOLR1 as a CAR T cell target. The Journal of clinical investigation 43 36136600
2016 Mechanistic target of rapamycin (mTOR) regulates trophoblast folate uptake by modulating the cell surface expression of FR-α and the RFC. Scientific reports 42 27562465
2018 A Single-Agent Dual-Specificity Targeting of FOLR1 and DR5 as an Effective Strategy for Ovarian Cancer. Cancer cell 35 30107179
2016 Neurological improvement following intravenous high-dose folinic acid for cerebral folate transporter deficiency caused by FOLR-1 mutation. European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society 35 27328863
2015 Folic acid inhibits COLO-205 colon cancer cell proliferation through activating the FRα/c-SRC/ERK1/2/NFκB/TP53 pathway: in vitro and in vivo studies. Scientific reports 35 26056802
2024 The efficacy and safety of mirvetuximab soravtansine in FRα-positive, third-line and later, recurrent platinum-sensitive ovarian cancer: the single-arm phase II PICCOLO trial. Annals of oncology : official journal of the European Society for Medical Oncology 34 39617145
2010 Association of folate receptor (FOLR1, FOLR2, FOLR3) and reduced folate carrier (SLC19A1) genes with meningomyelocele. Birth defects research. Part A, Clinical and molecular teratology 34 20683905
2018 Combined use of EpCAM and FRα enables the high-efficiency capture of circulating tumor cells in non-small cell lung cancer. Scientific reports 32 29352248
2023 Recent advances in using folate receptor 1 (FOLR1) for cancer diagnosis and treatment, with an emphasis on cancers that affect women. Life sciences 30 37244363
2017 Modification of cytokine-induced killer cells with folate receptor alpha (FRα)-specific chimeric antigen receptors enhances their antitumor immunity toward FRα-positive ovarian cancers. Molecular immunology 30 28360017
2024 Phase 1b study of mirvetuximab soravtansine, a folate receptor alpha (FRα)-targeting antibody-drug conjugate, in combination with carboplatin and bevacizumab in patients with platinum-sensitive ovarian cancer. Gynecologic oncology 29 38447347
2016 Promising Nanocarriers for PEDF Gene Targeting Delivery to Cervical Cancer Cells Mediated by the Over-expressing FRα. Scientific reports 28 27576898
2023 Cancer-associated fibroblasts induce sorafenib resistance of hepatocellular carcinoma cells through CXCL12/FOLR1. BMC cancer 26 38057830
2021 Reinforcing one-carbon metabolism via folic acid/Folr1 promotes β-cell differentiation. Nature communications 26 34099692
2010 The role of folate receptor alpha (FRalpha) in the response of malignant pleural mesothelioma to pemetrexed-containing chemotherapy. British journal of cancer 26 20051956
2007 Differentially expressed genes in embryonic cardiac tissues of mice lacking Folr1 gene activity. BMC developmental biology 25 18028541
2016 Severe leukoencephalopathy with cortical involvement and peripheral neuropathy due to FOLR1 deficiency. Brain & development 24 27743887
2013 Effects of parental folate deficiency on the folate content, global DNA methylation, and expressions of FRα, IGF-2 and IGF-1R in the postnatal rat liver. Nutrition research and practice 24 23964315
2020 CIC de novo loss of function variants contribute to cerebral folate deficiency by downregulating FOLR1 expression. Journal of medical genetics 23 32820034
2022 High Expression of Folate Receptor Alpha (FOLR1) is Associated With Aggressive Tumor Behavior, Poor Response to Chemoradiotherapy, and Worse Survival in Rectal Cancer. Technology in cancer research & treatment 22 36426547
2016 Evaluation of folate receptor 1 (FOLR1) mRNA expression, its specific promoter methylation and global DNA hypomethylation in type I and type II ovarian cancers. BMC cancer 22 27485273
2013 Structural and functional insights on folate receptor α (FRα) by homology modeling, ligand docking and molecular dynamics. Journal of molecular graphics & modelling 22 23880302
2010 Effect of antiepileptic drugs and reactive oxygen species on folate receptor 1 (FOLR1)-dependent 5-methyltetrahydrofolate transport. Molecular genetics and metabolism 22 20619709
2021 Conjugated β-Cyclodextrin Enhances the Affinity of Folic Acid towards FRα: Molecular Dynamics Study. Molecules (Basel, Switzerland) 21 34500740
2014 Sensory stimulus-sensitive drop attacks and basal ganglia calcification: new findings in a patient with FOLR1 deficiency. Epileptic disorders : international epilepsy journal with videotape 21 24556562
2019 Circulating Tumor Cell Detection In Epithelial Ovarian Cancer Using Dual-Component Antibodies Targeting EpCAM And FRα. Cancer management and research 19 32021417
2016 FolR1: a novel cell surface marker for isolating midbrain dopamine neural progenitors and nascent dopamine neurons. Scientific reports 19 27580818
2024 Maintenance with mirvetuximab soravtansine plus bevacizumab vs bevacizumab in FRα-high platinum-sensitive ovarian cancer. Future oncology (London, England) 18 39082675
2021 Novel Anti-FOLR1 Antibody-Drug Conjugate MORAb-202 in Breast Cancer and Non-Small Cell Lung Cancer Cells. Antibodies (Basel, Switzerland) 18 33535554
2013 Valproic acid substantially downregulated genes folr1, IGF2R, RGS2, COL6A3, EDNRB, KLF6, and pax-3, N-acetylcysteine alleviated most of the induced gene alterations in chicken embryo model. Romanian journal of morphology and embryology = Revue roumaine de morphologie et embryologie 18 24398995
2009 A novel approach identified the FOLR1 gene, a putative regulator of milk protein synthesis. Mammalian genome : official journal of the International Mammalian Genome Society 18 19669235
1999 DNA vaccination against the ovarian carcinoma-associated antigen folate receptor alpha (FRalpha) induces cytotoxic T lymphocyte and antibody responses in mice. Cancer gene therapy 18 10419053
2006 Novel mutations in the 5'-UTR of the FOLR1 gene. Clinical chemistry and laboratory medicine 17 16475900
2025 FOLR1 as a therapeutic target in platinum-resistant ovarian carcinoma: unique expression patterns across ovarian carcinoma histotypes and molecular subtypes of low-grade serous carcinoma. Journal of gynecologic oncology 16 40150910
2021 Heterocyclic Substitutions Greatly Improve Affinity and Stability of Folic Acid towards FRα. an In Silico Insight. Molecules (Basel, Switzerland) 16 33670773
2020 Correlation between the expression of folate receptor alpha (FRα) and clinicopathological features in patients with lung adenocarcinoma. Lung cancer (Amsterdam, Netherlands) 16 32450493
2019 Folic acid modifies the shape of epithelial cells during morphogenesis via a Folr1 and MLCK dependent mechanism. Biology open 16 30670450
2018 FOLR1 increases sensitivity to cisplatin treatment in ovarian cancer cells. Journal of ovarian research 16 29433550
2017 Folic acid inhibits nasopharyngeal cancer cell proliferation and invasion via activation of FRα/ERK1/2/TSLC1 pathway. Bioscience reports 16 29070520
2014 Structural and dynamic investigation of bovine folate receptor alpha (FOLR1), and role of ultra-high temperature processing on conformational and thermodynamic characteristics of FOLR1-folate complex. Colloids and surfaces. B, Biointerfaces 15 25023142
2024 A phase I study of Mirvetuximab Soravtansine and gemcitabine in patients with FRα-positive recurrent ovarian, primary peritoneal, fallopian tube, or endometrial cancer, or triple negative breast cancer. Gynecologic oncology 13 38262235
2024 Characterizing the genomic landscape through the lens of FOLR1 status in low and high grade serous ovarian carcinoma. Gynecologic oncology 13 39366033
2020 Identification of folate receptor α (FRα) binding oligopeptides and their evaluation for targeted virotherapy applications. Cancer gene therapy 13 31902944
2014 Polymorphisms of PRLR and FOLR1 genes and association with milk production traits in goats. Genetics and molecular research : GMR 13 24615071
2024 Analysis of real world FRα testing in ovarian, fallopian tube, and primary peritoneal cancers. Gynecologic oncology 12 39631181
2014 Down-regulation of FRα inhibits proliferation and promotes apoptosis of cervical cancer cells in vitro. Asian Pacific journal of cancer prevention : APJCP 12 25081683
2024 Dolutegravir induces FOLR1 expression during brain organoid development. Frontiers in molecular neuroscience 11 38828282
2021 Quantitative proteomics identifies FOLR1 to drive sorafenib resistance via activating autophagy in hepatocellular carcinoma cells. Carcinogenesis 11 33677528
2021 Cerebral folate deficiency in two siblings caused by biallelic variants including a novel mutation of FOLR1 gene: Intrafamilial heterogeneity following early treatment and the role of ketogenic diet. JIMD reports 11 34258135
2020 Epigenetic regulation of folate receptor-α (FOLR1) in human placenta of preterm newborns. Placenta 11 32421530
2019 microRNA-29b inhibits cell growth and promotes sensitivity to oxaliplatin in colon cancer by targeting FOLR1. BioFactors (Oxford, England) 11 31621972
2015 Genetic Variation in Renal Expression of Folate Receptor 1 (Folr1) Gene Predisposes Spontaneously Hypertensive Rats to Metabolic Syndrome. Hypertension (Dallas, Tex. : 1979) 11 26667416
2012 Expression of genes FOLR1, BAG1 and LAPTM4B in functioning and non-functioning pituitary adenomas. Folia neuropathologica 11 23023342
2025 Safety and efficacy of mirvetuximab soravtansine, a folate receptor alpha (FRα)-targeting antibody-drug conjugate (ADC), in combination with pembrolizumab in patients with platinum-resistant ovarian cancer. Gynecologic oncology 10 40700855
2024 Development of an FRα Companion Diagnostic Immunohistochemical Assay for Mirvetuximab Soravtansine. Archives of pathology & laboratory medicine 10 38282564
2021 Cerebral folate transporter deficiency syndrome in three siblings: Why genetic testing for developmental and epileptic encephalopathies should be performed early and include the FOLR1 gene. American journal of medical genetics. Part A 10 34008900
2020 First case report of cerebral folate deficiency caused by a novel mutation of FOLR1 gene in a Chinese patient. BMC medical genetics 10 33243190
2023 FOLR1-induced folate deficiency reduces viral replication via modulating APOBEC3 family expression. Virologica Sinica 9 37028598
2023 BiTE secretion by adoptively transferred stem-like T cells improves FRα+ ovarian cancer control. Journal for immunotherapy of cancer 9 37647218
2021 Identification of proteins related with pemetrexed resistance by iTRAQ and PRM-based comparative proteomic analysis and exploration of IGF2BP2 and FOLR1 functions in non-small cell lung cancer cells. Journal of proteomics 8 33561557
2017 Expression and characterization of the zebrafish orthologue of the human FOLR1 gene during embryogenesis. Gene expression patterns : GEP 8 28826993
2014 Decitabine impact on the endocytosis regulator RhoA, the folate carriers RFC1 and FOLR1, and the glucose transporter GLUT4 in human tumors. Clinical epigenetics 8 24401732
2014 [FRα: a target for prophylactic photodynamic therapy of ovarian peritoneal metastasis?]. Bulletin du cancer 8 25532689
2011 Altered signal transduction in Folr1-/- mouse embryo fibroblasts. Cell biology international 8 21649587
2018 Dissecting the role of Folr1 and Folh1 genes in the pathogenesis of metabolic syndrome in spontaneously hypertensive rats. Physiological research 7 30113208
2025 A dual-targeting peptide-drug conjugate based on CXCR4 and FOLR1 inhibits triple-negative breast cancer. Acta pharmaceutica Sinica. B 6 41132836
2007 Mutations in exons 2 and 3 of the FOLR1 gene in demented and non-demented elderly subjects. International journal of molecular medicine 6 17912458
2024 PARP-1, EpCAM, and FRα as potential targets for intraoperative detection and delineation of endometriosis: a quantitative tissue expression analysis. Reproductive biology and endocrinology : RB&E 5 39085882
2023 FOLR1 Gene Variation With Adult-Onset Cerebral Folate Deficiency and Stable Clinical and MRI Features up to 2 Years. Neurology. Genetics 5 38239817
2024 Exosomal or follicular FNDC3A decreases FOLR1 mRNA abundance and progesterone and lactate synthesis in bovine granulosa cells. Reproduction (Cambridge, England) 4 38513348
2025 NSD2 mediated H3K36me2 promotes pulmonary arterial hypertension by recruiting FOLR1 and metabolism reprogramming. Cellular signalling 3 39798773
2025 Patient outcomes in advanced ovarian cancer treated with an anti-FOLR1 antibody-drug conjugate. Gynecologic oncology 3 40121972
2025 The Anti-FRα Antibody-Drug Conjugate Luveltamab Tazevibulin Demonstrates Efficacy in Non-Small Cell Lung Cancer Preclinical Models and Induces Immunogenic Cell Death. Molecular cancer therapeutics 3 40293943
2025 Folate receptor alpha (FRα/FOLR1) and HER2 immunohistochemical staining in high-grade endometrial carcinoma with aberrant p53 expression. Histopathology 3 40769949
2024 Expression of the Folate Receptor Proteins FOLR1 and FOLR2 in Correlation With Clinicopathological Variables of Gastric Cancer. Cureus 3 38915965
2024 Identification and Characterization of Fully Human FOLR1-Targeting CAR T Cells for the Treatment of Ovarian Cancer. Cells 3 39594628
2023 Reduced YAP1 and FOLR1 in gliomas predict better response to chemotherapeutics. Cellular signalling 3 37269960
2023 FOLR1-stabilized β-catenin promotes laryngeal carcinoma progression through EGFR/AKT/GSK-3β pathway. Molecular carcinogenesis 3 37702010
2022 Association of polymorphisms of FOLR1 gene and FOLR2 gene and maternal folic acid supplementation with risk of ventricular septal defect: a case-control study. European journal of clinical nutrition 3 35273364

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