Affinage

FGL1

Fibrinogen-like protein 1 · UniProt Q08830

Length
312 aa
Mass
36.4 kDa
Annotated
2026-06-09
64 papers in source corpus 26 papers cited in narrative 25 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

FGL1 (HFREP-1) is a liver-secreted fibrinogen-domain protein that lacks the platelet-binding, cross-linking, and thrombin-sensitive elements required to form fibrin clots (PMID:8390249), and which functions principally as a major functional ligand for the immune checkpoint receptor LAG-3, engaging LAG-3 through its fibrinogen domain to inhibit T cell activation and cytokine secretion (PMID:34526102, PMID:35111155). In the liver microenvironment, hepatocyte-derived FGL1 acts via LAG-3 to suppress CD8+ T and NK cell function, and its genetic deletion or antibody blockade restores cytotoxic lymphocyte numbers and restrains liver metastasis (PMID:38973608); the same axis constrains Treg suppressive activity and skews CD4+ T cell cytokine output (PMID:37916085), drives M2 macrophage polarization through TNFR1/NF-κB suppression to promote liver repair (PMID:41548433), and delays autoimmune onset by regulating T cell homeostasis (PMID:40395191). FGL1 expression is induced by inflammatory IL-6 signaling in hepatocytes (PMID:37916085), and its transcription is controlled by a convergent set of regulators including STAT3—itself licensed by KDM4A-mediated H3K9me3 demethylation at the promoter (PMID:39085849) and by HDAC1-dependent JAK1 stability (PMID:39384195)—as well as YY1 (PMID:36268014), PRDM1 acting downstream of USP7 (PMID:38589688), PRMT5-methylated TCF12 (PMID:40041915), and SET1A-Yap in KRAS-driven tumors (PMID:39340215). FGL1 protein abundance is set by opposing ubiquitin machinery, with the E3 ligases FBXO38 (PMID:37938970) and IRF1-induced TRIM21 (PMID:42020516) promoting proteasomal degradation while the deubiquitinase OTUD1, induced by macrophage NF-κB signaling, stabilizes the protein to drive metastasis (PMID:37872170); an atypical glucosyl-galactosyl-hydroxylation at Lys65 catalyzed by LH3/GLT25D1 further stabilizes FGL1 (PMID:33984770). Independently of immune signaling, FGL1 suppresses hepcidin synthesis by directly binding BMP6 to block BMP-SMAD signaling, linking it to iron homeostasis during anemia recovery (PMID:38232308). An earlier body of work also defined FGL1 as a hepatocellular carcinoma growth suppressor whose tumor-restraining activity depends on an intact fibrinogen domain (PMID:14981537), a role that contrasts with its pro-tumor immune-evasive functions in other contexts.

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1993 Medium

    Established FGL1 as a liver- and HCC-expressed fibrinogen-family protein structurally incapable of clot formation, defining it as a secreted fibrinogen-domain protein rather than a coagulation factor.

    Evidence Subtractive cDNA cloning, sequence analysis, and Northern blot

    PMID:8390249

    Open questions at the time
    • No receptor or binding partner identified
    • Functional role undefined at discovery
  2. 2004 High

    Showed that FGL1 restrains tumor growth, answering whether its liver/HCC expression reflects a functional role and assigning it a growth-suppressor activity dependent on intact protein sequence.

    Evidence Gene restoration, antisense knockdown, soft agar and nude mouse xenograft assays with missense mutants

    PMID:14981537

    Open questions at the time
    • Mechanism of growth suppression not defined
    • Hard to reconcile with later pro-tumor immune-evasion roles
  3. 2016 Medium

    Demonstrated FGL1 can oligomerize with FGL2 in a distinct tissue context, indicating partner-dependent complex formation outside the liver-tumor axis.

    Evidence Proteomics, co-IP, and in situ localization in epididymis

    PMID:27732889

    Open questions at the time
    • Functional consequence of FGL1-FGL2 binding to spermatozoa unresolved
    • Relevance to systemic FGL1 biology unclear
  4. 2021 High

    Identified LAG-3 as FGL1's major functional receptor and mapped the interaction to FGL1's fibrinogen domain and LAG-3 D1-D2, establishing FGL1 as an immune checkpoint ligand that inhibits T cell activation.

    Evidence Binding assays and T cell co-culture functional assays replicated across labs

    PMID:34526102 PMID:35111155

    Open questions at the time
    • Structural basis of the interaction not detailed in timeline
    • Signaling events downstream of LAG-3 engagement not resolved here
  5. 2021 High

    Resolved how FGL1 protein levels are post-translationally maintained by identifying an atypical Lys65 glucosyl-galactosyl-hydroxylation that stabilizes the protein.

    Evidence LC-MS/MS, CRISPR knockout of LH3/GLT25D1, and site-directed mutagenesis

    PMID:33984770

    Open questions at the time
    • How GGH alters folding/secretion mechanistically not defined
    • Whether the modification affects LAG-3 binding untested
  6. 2021 Medium

    Began defining FGL1 transcriptional control and a non-immune intracellular partner, showing YY1 drives FGL1 and FGL1 binds MYH9 to promote lung adenocarcinoma proliferation.

    Evidence ChIP, luciferase, Co-IP/MS, and proliferation assays in LUAD

    PMID:36268014

    Open questions at the time
    • Mechanism by which intracellular FGL1-MYH9 promotes proliferation unclear
    • Relationship to secreted/checkpoint FGL1 pool not addressed
  7. 2023 High

    Established opposing ubiquitin-system control of FGL1 abundance, with FBXO38 ubiquitylating FGL1 for degradation and macrophage-induced OTUD1 deubiquitinating it, linking FGL1 stability to tumor immune evasion and metastasis.

    Evidence Co-IP, ubiquitination assays, ligase/DUB perturbation, and in vivo metastasis models

    PMID:37872170 PMID:37938970

    Open questions at the time
    • Quantitative balance between ligase and DUB in normal physiology unknown
    • Degron on FGL1 not mapped
  8. 2023 Medium

    Extended the LAG-3 axis beyond conventional T cells, showing FGL1 limits Treg suppressive function and shifts CD4+ cytokine output, and that hepatocyte FGL1 is IL-6 inducible.

    Evidence Flow cytometry, ELISA, antibody blockade, and cytokine-stimulated hepatocytes

    PMID:37916085

    Open questions at the time
    • Direct LAG-3 dependence of each cytokine effect not fully dissected
    • In vivo relevance to autoimmunity limited at this stage
  9. 2024 High

    Defined a hepcidin-suppressing, iron-regulatory function for FGL1 independent of immune signaling, via direct BMP6 binding and BMP-SMAD inhibition.

    Evidence Fgl1 knockout mice, in vitro BMP6 binding, and hepcidin/SMAD pathway readouts

    PMID:38232308

    Open questions at the time
    • Structural basis of FGL1-BMP6 binding undefined
    • Crosstalk with FGL1's LAG-3 role not explored
  10. 2024 High

    Established the in vivo liver immunology of FGL1, showing hepatocyte FGL1 suppresses CD8+ T and NK cells through LAG-3 and that its blockade restrains metastasis in a cytotoxic-lymphocyte-dependent manner.

    Evidence Fgl1 knockout mice, anti-FGL1 mAb, LAG-3 inhibition assays, cell depletion and adoptive transfer

    PMID:38973608

    Open questions at the time
    • Contribution of NK vs T cells to specific tumor types not separated
    • Therapeutic window of FGL1 blockade undefined
  11. 2024 High

    Assembled the upstream transcriptional and epigenetic network driving FGL1, converging on STAT3 (licensed by KDM4A demethylation and HDAC1/JAK1 stability), PRDM1 (USP7-stabilized), PRMT5-methylated TCF12, SET1A-Yap, and IRF1-TRIM21 degradation, explaining context-dependent FGL1 levels in tumor immune evasion.

    Evidence ChIP, luciferase, Co-IP, mass spectrometry, methylation/acetylation assays, and in vivo tumor models

    PMID:38589688 PMID:39085849 PMID:39340215 PMID:39384195 PMID:40041915 PMID:42020516

    Open questions at the time
    • Hierarchy and tissue specificity among these regulators unresolved
    • Which inputs dominate in normal hepatocytes vs tumors unclear
  12. 2024 Medium

    Broadened FGL1's effector reach to innate immunity and additional cancers, showing LAG-3-dependent M2 macrophage polarization and FGL1 partners/effectors (CENPM, SOX5, IMPDH1) in diverse tumor contexts.

    Evidence Liver injury models, BMDM assays, Co-IP, rescue experiments in ACC/prostate/ESCC models

    PMID:38702629 PMID:39463328 PMID:39778025 PMID:41548433

    Open questions at the time
    • Whether these partner interactions are direct and reciprocal varies by study
    • Integration with the canonical secreted/LAG-3 pool unclear
  13. 2025 Medium

    Linked FGL1 to systemic autoimmunity, showing IL-6-induced hepatic FGL1 regulates T cell homeostasis and delays Sjögren-like disease onset.

    Evidence Fgl1-knockout mouse model of primary Sjögren disease with immunologic profiling

    PMID:40395191

    Open questions at the time
    • LAG-3 dependence in this model not formally proven
    • Translation to human disease untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How FGL1's roles as an HCC growth suppressor, a pro-tumor LAG-3 checkpoint ligand, and a hepcidin/iron regulator are reconciled within a single protein remains unresolved.
  • No unifying structural or signaling framework connecting tumor-suppressive and immune-evasive functions
  • Physiological vs pathological balance of the FGL1-LAG-3 axis undefined
  • Functional impact of the p.Trp256Leu hemostasis-associated variant not biochemically tested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 2 GO:0098772 molecular function regulator activity 2
Localization
GO:0005576 extracellular region 3
Pathway
R-HSA-168256 Immune System 4 R-HSA-1643685 Disease 2 R-HSA-162582 Signal Transduction 1
Partners
BMP6CENPMFBXO38FGL2LAG3MYH9SOX5TRIM21
Complex memberships
eFGL (FGL1-FGL2 disulfide-linked oligomer)

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1993 FGL1 (HFREP-1) was identified as a novel fibrinogen-related protein specifically expressed in liver and hepatocellular carcinoma. The deduced protein sequence contained a hydrophobic leader peptide and showed marked homology with beta- and gamma-subunits of fibrinogen, but lacked a platelet-binding site, cross-linking region, and thrombin-sensitive site, indicating it cannot form fibrin clots. Subtractive/differential cDNA cloning, sequence analysis, Northern blot Biochemical and biophysical research communications Medium 8390249
2004 LFIRE-1/HFREP-1 (FGL1) encodes a growth suppressor in hepatocellular carcinoma. Restoration of wild-type FGL1 expression in HCC cells inhibited anchorage-dependent and -independent growth in vitro and suppressed tumorigenicity in nude mice, whereas FGL1 missense mutations failed to do so. Antisense-mediated reduction of FGL1 enhanced cancer cell proliferation and colony formation. Exogenous gene restoration, antisense knockdown, colony formation assay, soft agar assay, nude mouse xenograft Oncogene High 14981537
2016 FGL1 forms disulfide-linked oligomers with FGL2 in the epididymis. These oligomers (eFGL) specifically bind nonviable spermatozoa in the cauda epididymidis. Co-immunoprecipitation using anti-FGL2 antibody demonstrated that both FGL1 and FGL2 are present in the soluble eFGL complex. FGL1 is expressed in principal cells of the proximal cauda epididymidis. Proteomics (LC-MS), PCR-based cloning, co-immunoprecipitation, immunocytochemistry, Northern blot, in situ hybridization The international journal of biochemistry & cell biology Medium 27732889
2020 FGL1 confers acquired resistance to gefitinib in NSCLC by regulating the PARP1/caspase-3 apoptosis pathway. FGL1 knockdown suppressed cell viability, reduced gefitinib IC50, and enhanced apoptosis in PC9/GR cells; mechanistically, FGL1 inhibition reduced PARP1 and caspase-3 expression upon gefitinib treatment. siRNA knockdown, CCK-8 assay, colony formation, flow cytometry, Western blot, mouse xenograft, immunohistochemistry Respiratory research Medium 32778129
2020 Oxysophocarpine sensitized LAG-3 immunotherapy against HCC by decreasing FGL1 expression through downregulation of IL-6-mediated JAK2/STAT3 signaling. This effect was specific to the LAG-3 pathway, as oxysophocarpine had little effect on CD8+ T cell cytotoxicity with PD-1, Tim-3, or TIGIT blockade. In vitro cell assays, in vivo subcutaneous tumor model, Western blot, flow cytometry Cancer medicine Medium 32810392
2021 FGL1 is a major functional ligand of the immune checkpoint receptor LAG-3 (lymphocyte activation gene 3). FGL1 binding to LAG-3 on T cells inhibits T cell activation and cytokine secretion. The D1-D2 domains of LAG-3 and the fibrinogen domain (FD) of FGL1 mediate this interaction. Binding assays, functional T cell co-culture assays (referenced across multiple papers as established finding) Journal of hematology & oncology High 34526102 35111155
2021 Glucosyl-galactosyl-hydroxylation (GGH) post-translational modification occurs at Lys65 of FGL1, despite FGL1 lacking a collagen-like domain. This modification is carried out by the glycosyltransferases LH3 and GLT25D1. Knockout of LH3 or GLT25D1 significantly inhibited glycosylation, and deficiency of GGH (via point mutation or glycosyltransferase knockout) reduced FGL1 protein levels. LC-MS/MS analysis, LH3/GLT25D1-knockout cell lines (CRISPR), site-directed mutagenesis, Western blot Biochemical and biophysical research communications High 33984770
2021 FGL1 promotes proliferation of lung adenocarcinoma (LUAD) cells in vitro and in vivo, and is transcriptionally regulated by the transcription factor YY1. FGL1 directly binds MYH9 (identified by immunoprecipitation and mass spectrometry) to promote LUAD cell proliferation. Immunoprecipitation, mass spectrometry, chromatin immunoprecipitation, dual luciferase reporter assay, in vitro and in vivo proliferation assays Frontiers in immunology Medium 36268014
2023 FBXO38, an E3 ubiquitin ligase, directly interacts with FGL1 and ubiquitylates it to promote its proteasomal degradation. Depletion of FBXO38 markedly augments FGL1 protein abundance, suppressing CD8+ T cell infiltration and enhancing tumor immune evasion. Co-immunoprecipitation, ubiquitination assay, FBXO38 knockout/knockdown, flow cytometry, Western blot Cell reports High 37938970
2023 Tumor-associated macrophages (TAMs) activate NF-κB by secreting TNFα/IL-1β in the liver microenvironment, which transcriptionally upregulates OTUD1 (a deubiquitinase). OTUD1 then enhances FGL1 protein stability via deubiquitination, promoting metastatic tumor progression. Mechanistic experiments in intraportal injection model, Western blot, ubiquitination assay, NF-κB reporter assay Nature communications High 37872170
2024 FGL1 is a potent suppressor of hepcidin synthesis. FGL1 exerts this activity by directly binding to BMP6, thereby inhibiting the canonical BMP-SMAD signaling cascade that controls hepcidin transcription. Deletion of Fgl1 in mice results in higher hepcidin levels at baseline and after bleeding, and FGL1 is induced in the liver in response to hypoxia during anemia recovery. Fgl1 knockout mice, in vitro binding assays (BMP6 binding), hepcidin quantification in vitro and in vivo, BMP-SMAD pathway analysis Blood High 38232308
2024 HDAC1 deacetylates JAK1; SAHA (HDACi) inhibits HDAC1, increasing acetylation of JAK1 at lysine 1109, promoting its proteasomal degradation and reducing STAT3-driven FGL1 transcription. This mechanism underlies SAHA-mediated suppression of FGL1 and enhancement of CD8+ T cell antitumor activity in lung adenocarcinoma. Co-immunoprecipitation, chromatin immunoprecipitation, mass spectrometry, RNA sequencing, Western blot, ELISA, in vitro co-culture, in vivo tumor models Journal for immunotherapy of cancer High 39384195
2024 USP7 deubiquitinates the transcription factor PRDM1, stabilizing it. PRDM1 then transcriptionally activates FGL1 expression in liver cancer cells, attenuating CD8+ T cell activity. A positive feedback loop exists in which PRDM1 also transcriptionally stimulates USP7. Co-immunoprecipitation, ubiquitination assay, knockdown/overexpression, chromatin immunoprecipitation, in vivo xenograft, flow cytometry Acta pharmacologica Sinica Medium 38589688
2024 PRMT5 catalyzes symmetric dimethylation of transcription factor TCF12 at arginine 554 (R554), promoting TCF12 binding to the FGL1 promoter and transcriptionally activating FGL1 in liver cancer cells. Methylation-deficient TCF12-R554 mutants fail to activate FGL1 transcription, and PRMT5 inhibition reduces FGL1 and enhances CD8+ T cell antitumor immunity. In vitro methylation assay, site-directed mutagenesis, chromatin immunoprecipitation, luciferase reporter assay, in vivo tumor models, flow cytometry Acta pharmaceutica Sinica. B High 40041915
2024 KDM4A interacts with STAT3 and facilitates removal of methyl groups from H3K9me3 at the FGL1 promoter, enhancing STAT3-mediated transcription of FGL1 in NSCLC cells. STAT3 acts as a direct transcription factor for FGL1 by binding its promoter. Co-immunoprecipitation, chromatin immunoprecipitation, FGL1 promoter activity assay, Western blot, cell proliferation/migration assays Journal of experimental & clinical cancer research : CR Medium 39085849
2024 KRAS activates ERK1/2, which phosphorylates SET1A histone methyltransferase, increasing its stability and nuclear localization. SET1A-mediated methylation of Yap promotes its nuclear sequestration, driving Yap-induced transcription of FGL1 to promote immune evasion in KRAS-driven lung adenocarcinoma. Chromatin immunoprecipitation, dual luciferase reporter assay, lentiviral overexpression/silencing, flow cytometry, immunofluorescence, in vivo mouse models Cancer communications Medium 39340215
2024 Hepatocyte-derived FGL1 directly inhibits hepatic CD8+ T and NK cell functions via the receptor LAG-3 in the liver microenvironment. Fgl1-deficient mice showed increased hepatic CD8+ T and NK cell numbers and functions, and anti-FGL1 mAb blockade restrained liver metastasis. The antitumor efficacy of FGL1 blockade was dependent on cytotoxic T lymphocytes and NK cells as demonstrated by cell-deficient models and cell transfer in vivo. Fgl1 knockout mice, anti-FGL1 mAb treatment, in vitro inhibition assays with LAG-3, cell depletion models, adoptive cell transfer, flow cytometry JCI insight High 38973608
2024 TRIM21 (an E3 ubiquitin ligase) targets FGL1 for proteasomal degradation, and this process is transcriptionally regulated by IRF1 (which activates TRIM21 transcription). Artemisinin upregulates the IRF1-TRIM21 axis, promoting FGL1 degradation and enhancing antitumor CTL activity. Western blot, ubiquitination assay, luciferase reporter assay, chromatin immunoprecipitation, in vivo tumor models, flow cytometry Communications biology Medium 42020516
2024 CENPM physically interacts with FGL1 in adrenocortical carcinoma cells, as demonstrated by co-immunoprecipitation and DIA quantitative proteomics. Overexpression of FGL1 rescued migration and invasion of CENPM knockdown ACC cells, placing FGL1 downstream of CENPM in ACC metastasis. DIA quantitative proteomics, co-immunoprecipitation, immunofluorescence, Western blot, migration/invasion assays, xenograft model Clinical and translational medicine Medium 39778025
2024 FGL1 secreted from cancer-associated fibroblast (CAF)-derived exosomes interacts with SOX5 in prostate cancer cells and negatively regulates SOX5 expression, promoting PC cell viability, migration, and invasion via the FGL1/SOX5 axis. Co-immunoprecipitation, FISH, CCK-8, Transwell assay, rescue experiments, in vivo tumor model Histology and histopathology Low 39463328
2024 Radiation-induced upregulation of FGL1 in esophageal squamous cell carcinoma is mediated by the transcription factor FOXO4. FGL1 promotes ESCC metastasis through upregulation of IMPDH1; IMPDH1 knockdown reversed the pro-invasive effects of FGL1. qRT-PCR, Western blot, immunofluorescence, Transwell assay, wound healing, RNA sequencing, nude mouse models, rescue experiments BMC cancer Medium 38702629
2023 FGL1 binding to LAG3 inhibits Treg cell proliferation and impairs the suppressive activity of Treg cells by limiting IL-10 secretion, and promotes pathogenic IL-17a and IL-21 production by CD4+ T cells. FGL1 expression in hepatocytes is induced by the inflammatory cytokine IL-6 signaling. Flow cytometry, ELISA, cell culture assays with functional antibody blockade, hepatocyte stimulation with cytokines Heliyon Medium 37916085
2025 FGL1 binding to LAG3 on macrophages leads to downregulation of TNFR1 expression and suppression of NF-κB signaling, promoting M2 macrophage polarization while inhibiting M1 activation and thereby enhancing liver repair. Acute liver injury mouse models, bone marrow-derived macrophage experiments, Western blot, cytokine measurement, flow cytometry International immunopharmacology Medium 41548433
2021 An exome-wide association study identified an uncommon coding variant p.Trp256Leu in FGL1 that is associated with increased plasma D-dimer levels, supporting a role for FGL1 in hemostasis/fibrinolysis. Exome-wide association study, meta-analysis of 12 cohorts (n=19,306 for D-dimer), replication cohort Journal of thrombosis and haemostasis : JTH Low 33876560
2025 FGL1 produced by the liver is induced by IL-6 from CD4+ T cells in a primary Sjögren disease mouse model. FGL1 regulates naive and memory T cell homeostasis; Fgl1-deficient pSjD model mice showed earlier onset of autoimmune lesions compared to wild-type, indicating FGL1 suppresses T cell activation and delays autoimmunity onset. Fgl1-knockout mouse model of pSjD, immunologic analyses, genomic/bioinformatic analyses, cytokine measurement Arthritis & rheumatology Medium 40395191

Source papers

Stage 0 corpus · 64 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2022 Immune Checkpoint LAG3 and Its Ligand FGL1 in Cancer. Frontiers in immunology 137 35111155
2020 Expression and clinical significance of LAG-3, FGL1, PD-L1 and CD8+T cells in hepatocellular carcinoma using multiplex quantitative analysis. Journal of translational medicine 114 32762721
2021 Fibrinogen-like protein 1 (FGL1): the next immune checkpoint target. Journal of hematology & oncology 107 34526102
2020 FGL1 regulates acquired resistance to Gefitinib by inhibiting apoptosis in non-small cell lung cancer. Respiratory research 87 32778129
1993 Molecular cloning and initial characterization of a novel fibrinogen-related gene, HFREP-1. Biochemical and biophysical research communications 70 8390249
2023 The liver microenvironment orchestrates FGL1-mediated immune escape and progression of metastatic colorectal cancer. Nature communications 57 37872170
2004 LFIRE-1/HFREP-1, a liver-specific gene, is frequently downregulated and has growth suppressor activity in hepatocellular carcinoma. Oncogene 57 14981537
2021 Engineered Small Extracellular Vesicles as a FGL1/PD-L1 Dual-Targeting Delivery System for Alleviating Immune Rejection. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 54 34738731
2020 Oxysophocarpine suppresses hepatocellular carcinoma growth and sensitizes the therapeutic blockade of anti-Lag-3 via reducing FGL1 expression. Cancer medicine 38 32810392
2019 Loss of FGL1 induces epithelial‑mesenchymal transition and angiogenesis in LKB1 mutant lung adenocarcinoma. International journal of oncology 33 31322182
2024 HDAC inhibitor SAHA enhances antitumor immunity via the HDAC1/JAK1/FGL1 axis in lung adenocarcinoma. Journal for immunotherapy of cancer 31 39384195
2024 The hepatokine FGL1 regulates hepcidin and iron metabolism during anemia in mice by antagonizing BMP signaling. Blood 27 38232308
2022 Dual immunological and proliferative regulation of immune checkpoint FGL1 in lung adenocarcinoma: The pivotal role of the YY1-FGL1-MYH9 axis. Frontiers in immunology 24 36268014
2023 Development of a high-throughput TR-FRET screening assay for LAG-3/FGL1 interaction. SLAS discovery : advancing life sciences R & D 23 37121273
2023 Xue-Jie-San restricts ferroptosis in Crohn's disease via inhibiting FGL1/NF-κB/STAT3 positive feedback loop. Frontiers in pharmacology 23 37153794
2021 FGL1 as a Novel Mediator and Biomarker of Malignant Progression in Clear Cell Renal Cell Carcinoma. Frontiers in oncology 22 34956878
2024 Inhibition of USP7 enhances CD8+ T cell activity in liver cancer by suppressing PRDM1-mediated FGL1 upregulation. Acta pharmacologica Sinica 21 38589688
2023 Development of LAG-3/FGL1 blocking peptide and combination with radiotherapy for cancer immunotherapy. Acta pharmaceutica Sinica. B 21 38486998
2023 FBXO38 mediates FGL1 ubiquitination and degradation to enhance cancer immunity and suppress inflammation. Cell reports 20 37938970
2022 tRNA-derived fragment tRF-Glu49 inhibits cell proliferation, migration and invasion in cervical cancer by targeting FGL1. Oncology letters 19 36039056
2024 FGL1 and FGL2: emerging regulators of liver health and disease. Biomarker research 16 38816776
2021 Dual-targeting vaccine of FGL1/CAIX exhibits potent anti-tumor activity by activating DC-mediated multi-functional CD8 T cell immunity. Molecular therapy oncolytics 15 34977338
2024 Hepatocyte-derived FGL1 accelerates liver metastasis and tumor growth by inhibiting CD8+ T and NK cells. JCI insight 14 38973608
2024 FGL1: a novel biomarker and target for non-small cell lung cancer, promoting tumor progression and metastasis through KDM4A/STAT3 transcription mechanism. Journal of experimental & clinical cancer research : CR 14 39085849
2024 Yap methylation-induced FGL1 expression suppresses anti-tumor immunity and promotes tumor progression in KRAS-driven lung adenocarcinoma. Cancer communications (London, England) 13 39340215
2024 Impact of LAG-3/FGL1 pathway on immune evasive contexture and clinical outcomes in advanced urothelial carcinoma. Journal for immunotherapy of cancer 12 39043605
2023 Xue-Jie-San prevents the early development of colitis-associated intestinal fibrosis by blocking Notch1 and FGL1 signaling pathways. Journal of ethnopharmacology 12 37263315
2016 Two fibrinogen-like proteins, FGL1 and FGL2 are disulfide-linked subunits of oligomers that specifically bind nonviable spermatozoa. The international journal of biochemistry & cell biology 11 27732889
2024 A novel LAG3 neutralizing antibody improves cancer immunotherapy by dual inhibition of MHC-II and FGL1 ligand binding. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 9 38776682
2024 Vibrio splendidus infection promotes circRNA-FGL1-regulated coelomocyte apoptosis via competitive binding to Myc with the deubiquitinase OTUB1 in Apostichopus japonicus. PLoS pathogens 9 39146353
2024 FGL1 in plasma extracellular vesicles is correlated with clinical stage of lung adenocarcinoma and anti-PD-L1 response. Clinical and experimental immunology 8 38146642
2024 Tumor-intrinsic PRMT5 upregulates FGL1 via methylating TCF12 to inhibit CD8+ T-cell-mediated antitumor immunity in liver cancer. Acta pharmaceutica Sinica. B 8 40041915
2023 FGL1-LAG3 axis impairs IL-10-Producing regulatory T cells associated with Systemic lupus erythematosus disease activity. Heliyon 7 37916085
2025 Identification of CENPM as a key gene driving adrenocortical carcinoma metastasis via physical interaction with immune checkpoint ligand FGL1. Clinical and translational medicine 6 39778025
2023 Evaluation of Serum FGL1 as Diagnostic Markers for HBV-Related Hepatocellular Carcinoma. Laboratory medicine 6 36219698
2021 Involvement of LH3 and GLT25D1 for glucosyl-galactosyl-hydroxylation on non-collagen-like domain of FGL1. Biochemical and biophysical research communications 6 33984770
2024 Synthesis and Characterization of a Novel PET Tracer for Noninvasive Evaluation of FGL1 Status in Tumors. Molecular pharmaceutics 5 38836286
2024 Carvacrol potentiates immunity and sorafenib anti-cancer efficacy by targeting HIF-1α/STAT3/ FGL1 pathway: in silico and in vivo study. Naunyn-Schmiedeberg's archives of pharmacology 5 39466438
2022 Variations in Fibrinogen-like 1 (FGL1) Gene Locus as a Genetic Marker Related to Fat Deposition Based on Pig Model and Liver RNA-Seq Data. Genes 5 36011329
2021 FGL1 as a modulator of plasma D-dimer levels: Exome-wide marker analysis of plasma tPA, PAI-1, and D-dimer. Journal of thrombosis and haemostasis : JTH 5 33876560
2025 Research advances in FGL1/LAG3 for cancer diagnosis and treatment: From basics to clinical practice. Journal of cancer research and therapeutics 4 40317138
2025 Nanoengineered T cell membrane-coated nanodecoys blocking LAG-3/FGL1 to enhance cancer immunotherapy. Biomaterials 4 40957386
2023 FGL1 Promotes Tumor Immune Escape in Stomach Adenocarcinoma via the Notch Signaling Pathway. Molecular biotechnology 4 37902887
2025 Regulatory Role of FGL-1 in Interorgan Communication by Controlling T Cell Homeostasis During the Onset of Sjögren Disease. Arthritis & rheumatology (Hoboken, N.J.) 3 40395191
2025 The DCDC2/ENO1 axis promotes tumor progression and immune evasion in intrahepatic cholangiocarcinoma via activating FGL1-LAG3 checkpoint. Journal of experimental & clinical cancer research : CR 3 40533767
2024 Unlocking therapeutic potential: Targeting lymphocyte activation Gene-3 (LAG-3) with fibrinogen-like protein 1 (FGL1) in systemic lupus erythematosus. Journal of translational autoimmunity 3 39228513
2025 Expression and clinical significance of CD155, FGL1, Galectin-9, and PD‑L1 in breast cancer with neoadjuvant chemotherapy. Medical oncology (Northwood, London, England) 2 40711645
2025 IL-6 promotes metastasis and EMT of non-small cell lung cancer cells by up-regulating FGL1 via STAT3 pathway. Translational cancer research 2 40792131
2024 Cancer-associated fibroblast-secreted exosomes promote prostate cancer cell migration and invasion by the FGL1/SOX5 axis. Histology and histopathology 2 39463328
2023 The hepatokine FGL1 regulates hepcidin and iron metabolism during the recovery from hemorrhage-induced anemia in mice. bioRxiv : the preprint server for biology 2 37066218
2025 Development of Novel Peptide-Based Radiotracers for Detecting FGL1 Expression in Tumors. Molecular pharmaceutics 1 39893698
2025 Ablation of Hepatocyte Derived-FGL1 Does Not Aggravate Metabolic Dysfunction-Associated Steatotic Liver Disease. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 1 40832769
2024 Radiation-induced upregulation of FGL1 promotes esophageal squamous cell carcinoma metastasis via IMPDH1. BMC cancer 1 38702629
2024 FGL1 facilitates rather than suppresses anticancer immunity against microsatellite instable gastric cancer. Genes and immunity 1 39672971
2026 FGL1 as an Immune Checkpoint in the Immune Microenvironment of Bladder Cancer. Journal of immunotherapy (Hagerstown, Md. : 1997) 0 41439559
2026 The FGL1-LAG-3 axis attenuates melanoma-induced cachexia in mice. Cancer & metabolism 0 41501849
2026 FGL1 modulates macrophage function and enhances liver repair through LAG3-TNFR1 axis. International immunopharmacology 0 41548433
2026 Evaluation of FGL1 as a hepatokine marker in iron deficiency. Frontiers in nutrition 0 41867684
2026 Targeting IRF1-TRIM21 axis enhances anti-tumor immunity by promoting ubiquitin-mediated degradation of FGL1 in non-small cell lung cancer. Communications biology 0 42020516
2025 Silencing FGL1 promotes prostate cancer cell apoptosis and inhibits EMT progression. Scientific reports 0 40481127
2025 [Retracted] tRNA-derived fragment tRF-Glu49 inhibits cell proliferation, migration and invasion in cervical cancer by targeting FGL1. Oncology letters 0 40613030
2025 Transcriptional activation of FGL1 by KDM1A promotes immune evasion in lung cancer. Physiological genomics 0 40637489
2025 How effective is serum FGL1 measurement in assessing disease activity: A cross-sectional study in rheumatoid arthritis. Clinical biochemistry 0 40897229
2025 FGL1-mediated lymph node metastasis in stage T1 non-small cell lung cancer: therapeutic targeting. Experimental hematology & oncology 0 41024301

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