Affinage

FN1

Fibronectin · UniProt P02751

Length
2477 aa
Mass
272.3 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: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

FN1 encodes a secreted extracellular matrix glycoprotein that organizes cell adhesion, spreading, and migration by linking the cell surface to actin microfilament bundles, with surface FN1 forming fibrillar networks whose loss accompanies cellular transformation and loss of normal growth control (PMID:925079, PMID:616487, PMID:363730). FN1 colocalizes with actin bundles during cell spreading, implying a transmembrane connection that nucleates attachment plaques, and exogenous purified FN1 restores attachment, spreading, alignment, and migration to transformed cells (PMID:365353, PMID:667950). Its distribution is cell-type-specific and polarized—present at endothelial luminal surfaces and basal choroid epithelium—and is developmentally downregulated during myoblast fusion (PMID:321128, PMID:21348357). FN1 signals into cells chiefly through the α5β1 integrin (ITGA5/ITGB1), an interaction shown by co-immunoprecipitation and required for FN1-driven proliferation, migration, and invasion, which activates FAK/Src and downstream RhoA/Rac1/CDC42 GTPases as well as PI3K/AKT, NF-κB, STAT3 (via PTPRM promoter methylation), and YAP1/Hippo with SLC1A3-mediated aspartate uptake in multiple tumor contexts (PMID:29274284, PMID:31326465, PMID:35197128, PMID:34225581, PMID:37458908). FN1 transcription is directly driven by HMGA2, HOXA13, and GATA6 binding to its promoter and by the IRE1α–XBP1s axis, while FN1 protein is turned over through p62/SQSTM1-dependent autophagy-lysosome degradation (PMID:33318468, PMID:31326465, PMID:26964871, PMID:35197128, PMID:35088888). Beyond its matrix role, exercise-induced muscle-secreted FN1 acts as a circulating factor that engages hepatic α5β1 integrin and IKKα/β–JNK1–BECN1 signaling to activate hepatic autophagy and systemic insulin sensitization (PMID:36812915). Recurrent oncogenic FN1 gene fusions place receptor tyrosine kinase or growth-factor domains (FGFR1, FGF1, EGF, ACVR2A, FGFR2, MERTK, NTRK1, TEK) under FN1 promoter and secretion/membrane-targeting control, driving constitutive signaling across phosphaturic mesenchymal tumors, calcifying aponeurotic fibroma, synovial chondromatosis, and calcified chondroid mesenchymal neoplasms (PMID:27443518, PMID:26691015, PMID:31273315, PMID:33727696). A gain-of-function FN1 variant that raises integrin binding while reducing collagen IV (COL4A3/4) binding causes glomerular fibronectin deposition, and a rare FN1 variant modifies APOEε4-mediated Alzheimer's disease risk through altered blood-brain barrier clearance (PMID:38598053, PMID:36774238).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1978 Medium

    Established that FN1 (LETS protein) is a cell-surface/matrix glycoprotein physically and functionally coupled to the actin cytoskeleton, answering whether an adhesion molecule could transduce structure across the membrane.

    Evidence Immunofluorescence localization, cytoskeletal perturbants, and double-label co-localization with actin during cell spreading in cultured cells

    PMID:365353 PMID:925079

    Open questions at the time
    • No molecular identification of the transmembrane linker
    • Correlative co-localization does not prove direct receptor engagement
  2. 1978 Medium

    Demonstrated FN1 is a sufficient functional effector of adhesion and motility, since purified protein added back to transformed cells restored attachment, spreading, and migration—linking reduced surface FN1 to the transformed phenotype and growth control.

    Evidence Addition of purified LETS protein to normal/transformed cells, phagokinetic track migration assays, radioiodination quantification in somatic cell hybrids

    PMID:363730 PMID:616487 PMID:667950

    Open questions at the time
    • No receptor or signaling pathway identified at this stage
    • Growth-control correlation in hybrids is genetic association, not direct mechanism
  3. 1978 Medium

    Showed FN1 expression is cell-type-restricted, polarized, and developmentally regulated, indicating its deposition is spatially and temporally controlled rather than constitutive.

    Evidence Immunofluorescence across nervous tissue cell types and species; immunofluorescence/radioimmunoassay during myoblast fusion

    PMID:21348357 PMID:321128

    Open questions at the time
    • Transcriptional regulators driving polarization unknown
    • Functional consequence of downregulation during myogenesis not tested
  4. 2018 Medium

    Identified the integrin α5β1 receptor (ITGA5/ITGB1) as the direct functional partner mediating FN1's pro-tumorigenic effects, answering how secreted FN1 signals into cells.

    Evidence Co-immunoprecipitation and ITGA5 rescue of FN1 knockdown phenotypes in colorectal cancer cells; Co-IP of FN1-ITGA5/ITGB1 in gastric cancer

    PMID:29274284 PMID:35197128

    Open questions at the time
    • Binding interface and stoichiometry not defined
    • Single-cell-line Co-IP without structural validation
  5. 2019 Medium

    Connected FN1 to defined intracellular signaling cascades, showing it activates Src/FAK and downstream Rho-family GTPases to drive migration, with exogenous FN1 rescuing pathway activity.

    Evidence IRE1α/XBP1s ChIP on FN1 promoter, phosphorylation and GTPase activation assays, exogenous FN1 rescue in colon cancer

    PMID:31326465

    Open questions at the time
    • Receptor proximal to FAK/Src activation not directly demonstrated here
    • Single cancer context
  6. 2022 Medium

    Defined the transcriptional control of FN1, showing HMGA2, HOXA13, and GATA6 directly bind its promoter to drive FN1-dependent invasion and metastasis, while IRE1α-XBP1s provides a stress-responsive input.

    Evidence ChIP-PCR, dual-luciferase reporter assays, and FN1-overexpression rescue across colorectal, gastric, and oral squamous carcinoma models with in vivo validation

    PMID:26964871 PMID:35088888 PMID:35197128

    Open questions at the time
    • Combinatorial regulation among these factors unresolved
    • Promoter elements bound not finely mapped
  7. 2021 Medium

    Expanded the downstream signaling repertoire of FN1 to STAT3 (via PTPRM promoter methylation), NF-κB, PI3K/AKT, and YAP1/Hippo-coupled metabolic uptake, establishing FN1 as a node feeding multiple oncogenic pathways.

    Evidence Genetic/pharmacological manipulation with methylation-specific PCR, demethylation, pathway inhibitor combinations, multi-omics, and in vivo models in glioblastoma, breast, thyroid, and pancreatic cancer

    PMID:34225581 PMID:36278453 PMID:37458908 PMID:40678072

    Open questions at the time
    • Pathway selectivity across tumor types unexplained
    • Thyroid and pancreatic studies are correlative without direct FN1 rescue
  8. 2020 Medium

    Identified how FN1 protein levels are controlled post-translationally, showing p62/SQSTM1 acts as an autophagy adapter targeting FN1 to lysosomal degradation.

    Evidence Pharmacological autophagy/lysosome modulation, immunoprecipitation, and p62 mutant cell lines

    PMID:33318468

    Open questions at the time
    • Whether intracellular or secreted FN1 pool is degraded not fully resolved
    • Single Co-IP system
  9. 2023 High

    Revealed an endocrine role for FN1 beyond the matrix: exercise-induced muscle-secreted FN1 signals to liver via α5β1 integrin to activate hepatic autophagy and systemic insulin sensitization.

    Evidence Plasma proteomics, muscle-specific FN1 knockout, hepatic autophagy assays, integrin blockade, and insulin sensitization assays in mice

    PMID:36812915

    Open questions at the time
    • Human relevance of the muscle-liver FN1 axis not established
    • Distinction between this circulating FN1 and matrix FN1 forms unclear
  10. 2021 Medium

    Established recurrent FN1 gene fusions as defining oncogenic events, where the FN1 promoter and secretion/membrane-targeting domains drive constitutive RTK or growth-factor signaling across distinct mesenchymal tumors.

    Evidence RNA sequencing, FISH, Sanger breakpoint mapping, IHC, and Western blot across PMT, CAF, synovial chondromatosis, and calcified chondroid mesenchymal neoplasms

    PMID:26691015 PMID:27443518 PMID:31273315 PMID:33727696

    Open questions at the time
    • Functional reconstitution of fusion signaling largely predicted not directly assayed
    • Therapeutic targetability not tested in these series
  11. 2024 Medium

    Linked FN1 sequence variation directly to human disease through gain-of-function binding changes, providing mechanism for glomerular fibronectin deposition and a modifier role in Alzheimer's disease.

    Evidence Genetic sequencing with in vitro integrin/collagen IV binding assays for the c.3415G>A glomerulopathy variant; whole-genome association plus zebrafish fn1b loss-of-function for the APOEε4-protective variant

    PMID:36774238 PMID:38598053

    Open questions at the time
    • Causality of the Alzheimer's variant rests on ortholog modeling
    • Tissue-specific consequences of altered binding not fully characterized

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the distinct FN1 functional pools—matrix-bound adhesive fibronectin, autophagy-degraded intracellular FN1, and circulating endocrine FN1—are differentially produced, modified, and targeted to specific receptors and tissues remains unresolved.
  • No structural model of FN1-integrin engagement in the timeline
  • Mechanism distinguishing endocrine vs matrix FN1 function unknown
  • Whether fusion-driven signaling requires the same domains as native FN1 secretion untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098631 cell adhesion mediator activity 6 GO:0060089 molecular transducer activity 4 GO:0005198 structural molecule activity 2 GO:0048018 receptor ligand activity 2
Localization
GO:0005576 extracellular region 2 GO:0005886 plasma membrane 2 GO:0031012 extracellular matrix 2
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-1643685 Disease 5 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-1474244 Extracellular matrix organization 3 R-HSA-9612973 Autophagy 2
Partners
COL4A3ITGA5ITGB1SQSTM1

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1977 LETS protein (FN1) is located predominantly at the cell-substrate interface and in cell-cell contact regions in subconfluent cultures, and forms a fibrillar network in dense cultures; transformed cells show greatly reduced surface LETS protein. Perturbation experiments showed that actin microfilament bundles and LETS protein respond coordinately to certain perturbants, supporting a functional link between FN1 and cell adhesion/cytoskeleton. Immunofluorescence, cytoskeletal perturbation agents (cytochalasin, colchicine), cell morphology analysis The Journal of cell biology Medium 925079
1977 LETS protein (FN1) is synthesized and secreted by normal cells into the medium at higher rates than transformed cells; exogenous addition of purified LETS protein to transformed cells restores cell attachment, spreading, alignment, and actin cable formation, establishing a direct functional role for FN1 in cell adhesion and cytoskeletal organization. Immunoprecipitation, biosynthesis assays, addition of purified LETS protein to transformed cells, morphological readout Journal of supramolecular structure Medium 616487
1978 FN1 (LETS protein) colocalizes with actin microfilament bundles in a fibrillar pattern during and after cell spreading, with 80–100% correspondence when fibrillar patterns develop, suggesting a transmembrane relationship between microfilament bundles and FN1 that contributes to formation of attachment plaques. Double-label immunofluorescence for fibronectin and actin/intermediate filaments during cell spreading time course Cell Medium 365353
1978 Addition of purified LETS protein (FN1) to normal or transformed cells increases cell migration as measured by phagokinetic track formation on gold-coated coverslips and on plastic; added FN1 attaches in a fibrillar network with greater binding to normal than transformed cells. Phagokinetic track assay on gold particle-coated coverslips, cell migration on plastic, immunofluorescence of added protein Cell Medium 667950
1977 During myoblast fusion (myogenesis), the fibrillar surface distribution of LETS protein (FN1) disappears from myotubes and total LETS protein is quantitatively reduced, as measured by immunofluorescence and radioimmunoassay, establishing a regulated downregulation of FN1 during muscle differentiation. Indirect immunofluorescence, radioimmunoassay Cell Medium 321128
1978 LETS protein (FN1) is expressed on endothelial cells, choroid epithelial cells, fibroblasts, and leptomeningeal cells in the nervous system, but not on glial or neuronal cells; subcellular localization shows FN1 at the luminal surface of endothelial cells and at the basal end (not apical) of choroid epithelial cells, demonstrating cell-type-specific and polarized subcellular distribution. Immunofluorescence in mammalian and avian nervous tissue sections across developmental stages Brain research Medium 21348357
1978 In somatic cell hybrids, high levels of LETS protein (FN1) and extensive microfilament bundles correlate with normal growth control, while reduced or absent LETS protein correlates with transformed growth characteristics, supporting a role for FN1 in normal growth regulation linked to cytoskeletal organization. Lactoperoxidase-catalyzed radioiodination for LETS protein quantification, indirect immunofluorescence for actin/myosin, hybrid cell growth control assays Journal of cell science Medium 363730
2016 In phosphaturic mesenchymal tumors (PMTs), recurrent FN1-FGFR1 fusion genes (present in ~42% of cases) and a novel FN1-FGF1 fusion gene (present in ~6%) were identified; FN1-FGF1 fusion protein is predicted to be secreted and to serve as a ligand activating FGFR1 via an autocrine loop, implicating FN1 domain-driven FGF signaling in PMT pathogenesis. RNA sequencing, Sanger sequencing validation, FISH, western blot, immunohistochemistry Modern pathology Medium 27443518
2016 In calcifying aponeurotic fibroma (CAF), recurrent FN1-EGF fusion genes were identified; FN1 exons are fused to EGF exon 17 or 19, with strong FN1 promoter activity driving inappropriate expression of the biologically active EGF portion, detected immunohistochemically; this suggests an autocrine/paracrine EGF signaling mechanism driven by the FN1 promoter. Chromosome banding, FISH, RNA sequencing, RT-PCR, immunohistochemistry The Journal of pathology Medium 26691015
2019 FN1-ACVR2A rearrangements are recurrent in synovial chondromatosis (57%) and chondrosarcoma secondary to synovial chondromatosis (75%), as demonstrated by FISH and RNA sequencing; FN1 is also rearranged in soft tissue chondromas with FN1-FGFR2 fusions, establishing FN1 gene rearrangement as the defining molecular event in these cartilaginous tumors. FISH, RNA sequencing, RT-PCR Modern pathology Medium 31273315
2018 FN1 protein binds ITGA5 (integrin alpha-5) in colorectal cancer cells, as demonstrated by co-immunoprecipitation; ITGA5 overexpression reverses the suppression of proliferation, migration, invasion, and apoptosis caused by FN1 knockdown, establishing FN1-ITGA5 interaction as functionally required for FN1-mediated colorectal cancer tumorigenesis. siRNA knockdown, western blot, Co-IP for FN1-ITGA5 interaction, proliferation/migration/invasion assays, apoptosis assay Journal of cellular biochemistry Medium 29274284
2020 FN1 is degraded via the autophagy-lysosome pathway in a p62/SQSTM1-dependent manner: rapamycin and EBSS promote autophagy and increase FN1 degradation, autophagy inhibitors reduce FN1 degradation, and immunoprecipitation assays show p62/SQSTM1 physically interacts with FN1 as an autophagy adapter; p62 mutation abolishes this interaction. Pharmacological autophagy modulation, lysosomal/proteasomal inhibitors (MG132, bafilomycin A1, chloroquine), immunoprecipitation, p62 mutant cell lines International journal of oral science Medium 33318468
2023 Exercise induces skeletal muscle secretion of FN1 into circulation; muscle-secreted FN1 activates hepatic autophagy via the hepatic receptor α5β1 integrin and downstream IKKα/β-JNK1-BECN1 signaling pathway, mediating systemic insulin sensitization; this was demonstrated by proteomic identification of FN1 as an exercise-induced circulating factor, and by muscle-specific FN1 knockout experiments. Proteomics of exercise mouse plasma, muscle-specific knockout, hepatic autophagy assays, integrin receptor blocking, insulin sensitization assays Cell metabolism High 36812915
2019 IRE1α regulates colon cancer cell metastasis by controlling FN1 expression: IRE1α activates XBP1s, which binds the FN1 promoter to initiate FN1 transcription; FN1 in turn activates Src/FAK phosphorylation and downstream GTPases (RhoA, Rac1, CDC42); exogenous FN1 addition rescues Src/FAK phosphorylation and migration inhibited by IRE1α knockdown. IRE1α siRNA knockdown, XBP1s ChIP on FN1 promoter, exogenous FN1 rescue, Src/FAK phosphorylation assays, GTPase activation assays, migration/invasion assays The international journal of biochemistry & cell biology Medium 31326465
2016 HMGA2 directly binds the FN1 promoter and transcriptionally activates FN1 expression in colorectal cancer, as demonstrated by chromatin immunoprecipitation-PCR and luciferase assays; HMGA2-driven FN1 upregulation contributes to enhanced migration and invasion in vitro and metastasis in vivo. Chromatin immunoprecipitation (ChIP)-PCR, luciferase reporter assay, ectopic HMGA2 expression/silencing, in vivo metastasis model Carcinogenesis Medium 26964871
2022 HOXA13 directly binds the FN1 promoter region to enhance FN1 transcription, activating the FAK/Src signaling axis; co-immunoprecipitation confirmed that FN1 interacts with ITGA5 and ITGB1 (integrin α5β1) in gastric cancer cells; rescue experiments showed FN1 is required for HOXA13-mediated promotion of gastric cancer metastasis. ChIP, dual luciferase assay, Co-IP (FN1-ITGA5/ITGB1), FAK/Src phosphorylation assays, rescue experiments, in vivo model Experimental hematology & oncology Medium 35197128
2024 A rare FN1 variant (rs140926439) is protective against APOEε4-mediated Alzheimer's disease risk (OR=0.29) and delays age at onset; in zebrafish, loss-of-function mutations in fn1b (FN1 ortholog) reduced gliosis, enhanced gliovascular remodeling, and potentiated microglial response, suggesting that pathological FN1 accumulation at the blood-brain barrier impairs toxic protein clearance. Whole-genome sequencing, genetic association analysis, zebrafish loss-of-function models, immunofluorescence for gliosis and microglial markers Acta neuropathologica Medium 38598053
2021 In calcified chondroid mesenchymal neoplasms, FN1 fuses with multiple receptor tyrosine kinase genes (FGFR2, FGFR1, MERTK, NTRK1, TEK); breakpoints in FN1 range from exons 11–48 retaining signal peptide, FN1, FN2, and/or FN3 domains, while partner genes retain transmembrane and tyrosine kinase domains, suggesting FN1 acts as a membrane-targeting/secretion signal driving constitutive RTK activation. Targeted RNA-seq (115-gene panel), Sanger sequencing for breakpoint validation, FISH Modern pathology Medium 33727696
2023 A novel pathogenic FN1 mutation (c.3415G>A) causes glomerular fibronectin-specific deposition in a gain-of-function manner; the variant increases fibronectin binding to integrin (maintaining podocyte adhesion) but decreases fibronectin's capacity to bind COL4A3/4 (collagen IV), providing a mechanism for both the glomerulopathy and associated thin basement membrane nephropathy. Genetic sequencing, in vitro binding assays (FN1 variant vs. integrin and collagen IV), patient tissue analysis Pathology Medium 36774238
2021 FN1 promotes glioblastoma cell proliferation by inducing PTPRM promoter methylation, which reduces PTPRM expression and leads to increased STAT3 phosphorylation; FN1 overexpression decreases PTPRM protein, and demethylating agent 5-aza reverses FN1-induced STAT3 phosphorylation and cell viability, placing FN1 upstream of PTPRM methylation and STAT3 activation. Lentiviral overexpression/knockdown, methylation-specific PCR, 5-aza demethylation treatment, STAT3 inhibitor (stattic), western blot, cell viability assay Pharmaceutical biology Medium 34225581
2023 FN1 promotes breast cancer progression by activating the YAP1/Hippo pathway (via reduced YAP1 phosphorylation) and upregulating SLC1A3-mediated aspartate uptake; silencing FN1 enhances YAP1 phosphorylation, reduces aspartate uptake, and inhibits proliferation, invasion and migration; combined FN1 inhibition with YAP1 or SLC1A3 inhibitors synergistically suppresses tumor growth. FN1 siRNA knockdown, RNA-seq, LC-MS metabolomics, western blot, in vivo tumor models, YAP1/SLC1A3 inhibitor combination studies Breast cancer research and treatment Medium 37458908
2022 FN1 activates the FAK/Src signaling axis and downstream NF-κB pathway in thyroid carcinoma; overexpression of FN1 in MDA-T85 cells promoted growth, migration and invasion with increased p-IκB-α, p-IKK-β, and NF-κB p65 expression, while FN1 knockdown in MDA-T41 cells had the opposite effect. FN1 overexpression/knockdown, western blot for NF-κB pathway components, CCK-8, EDU, scratch, transwell assays Protein and peptide letters Low 36278453
2024 DPSCs-secreted FN1 promotes endothelial cell proliferation, migration, and tube formation via ITGA5 (integrin α5) and downstream PI3K/AKT signaling during dental pulp development; this was validated by FN1 recombinant protein treatment of HUVECs and in vivo mouse experiments. Single-cell sequencing, recombinant FN1 protein treatment, ITGA5 blocking, PI3K/AKT pathway inhibition, tube formation assay, in vivo mouse model, western blot Stem cell reviews and reports Medium 38418738
2025 CAF-derived FN1 activates the integrin-PI3K/AKT signaling pathway in pancreatic cancer cells to promote metastasis; combined inhibition of PI3K/AKT and integrins synergistically suppressed tumor invasion in vitro; high FN1 expression correlated with M2 macrophage/Treg immunosuppressive microenvironment. Transcriptomic/single-cell sequencing analysis, in vitro co-culture, Transwell invasion assay, PI3K/AKT inhibitor, integrin blocking, western blot Frontiers in oncology Low 40678072
2022 GATA6 transcription factor directly binds the FN1 promoter and activates FN1 transcription in oral squamous cell carcinoma; GATA6 knockdown-mediated suppression of proliferation, colony formation, invasion, and migration is rescued by FN1 overexpression. Dual-luciferase reporter assay, chromatin immunoprecipitation (ChIP), GATA6 knockdown/FN1 overexpression rescue experiments Molecular medicine reports Medium 35088888
2022 SOX2 transcriptionally upregulates FN1 expression in Schwann cell-like cells (iSCs), promoting proliferation and migration (fibronectin fibrillogenesis); exosomes secreted by iSCs also increase Schwann cell viability and migration; the SOX2/FN1 axis was demonstrated by RNA-seq and functional experiments in sciatic nerve repair. SC RNA-seq, SOX2 overexpression/knockdown, scratch wound assay, EdU proliferation assay, sciatic nerve transection animal model International journal of molecular medicine Low 35475578

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1978 Relationships between fibronectin (LETS protein) and actin. Cell 420 365353
1977 Surface distribution of LETS protein in relation to the cytoskeleton of normal and transformed cells. The Journal of cell biology 244 925079
1978 Effects of LETS glycoprotein on cell motility. Cell 243 667950
2019 Muscle metabolism and atrophy: let's talk about sex. Biology of sex differences 168 31462271
1978 Cellular and subcellular localization of LETS protein in the nervous system. Brain research 162 21348357
2007 Epigenetic programming by maternal behavior and pharmacological intervention. Nature versus nurture: let's call the whole thing off. Epigenetics 152 17965624
2016 Characterization of FN1-FGFR1 and novel FN1-FGF1 fusion genes in a large series of phosphaturic mesenchymal tumors. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 151 27443518
1977 Alteration in cell surface LETS protein during myogenesis. Cell 148 321128
2018 Down-regulation of FN1 inhibits colorectal carcinogenesis by suppressing proliferation, migration, and invasion. Journal of cellular biochemistry 146 29274284
2021 Let's talk about sex: Differences in drug therapy in males and females. Advanced drug delivery reviews 120 34015416
2019 Synovial chondromatosis and soft tissue chondroma: extraosseous cartilaginous tumor defined by FN1 gene rearrangement. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 82 31273315
2020 FN1 promotes chondrocyte differentiation and collagen production via TGF-β/PI3K/Akt pathway in mice with femoral fracture. Gene 81 33098939
2023 Sphingosine-1-phosphate derived from PRP-Exos promotes angiogenesis in diabetic wound healing via the S1PR1/AKT/FN1 signalling pathway. Burns & trauma 77 37251708
2009 Quantification of fibronectin 1 (FN1) splice variants, including two novel ones, and analysis of integrins as candidate FN1 receptors in bovine preimplantation embryos. BMC developmental biology 69 19126199
2020 Regulation of FN1 degradation by the p62/SQSTM1-dependent autophagy-lysosome pathway in HNSCC. International journal of oral science 67 33318468
2017 MicroRNA-200c binding to FN1 suppresses the proliferation, migration and invasion of gastric cancer cells. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 65 28113080
2021 Calcified chondroid mesenchymal neoplasms with FN1-receptor tyrosine kinase gene fusions including FGFR2, FGFR1, MERTK, NTRK1, and TEK: a molecular and clinicopathologic analysis. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 63 33727696
2016 Transcriptional activation of FN1 and IL11 by HMGA2 promotes the malignant behavior of colorectal cancer. Carcinogenesis 63 26964871
2016 FN1-EGF gene fusions are recurrent in calcifying aponeurotic fibroma. The Journal of pathology 61 26691015
2023 Exercise-activated hepatic autophagy via the FN1-α5β1 integrin pathway drives metabolic benefits of exercise. Cell metabolism 60 36812915
2022 Suppression of breast cancer-associated bone loss with osteoblast proteomes via Hsp90ab1/moesin-mediated inhibition of TGFβ/FN1/CD44 signaling. Theranostics 57 34976221
2018 Nicotine and electronic cigarette (E-Cig) exposure decreases brain glucose utilization in ischemic stroke. Journal of neurochemistry 52 30062776
2006 Hypoxia-regulated differentiation: let's step it up a Notch. Trends in molecular medicine 52 16513423
2022 Let's chat: Communication between electroactive microorganisms. Bioresource technology 51 35065228
2022 Let's phase it: viruses are master architects of biomolecular condensates. Trends in biochemical sciences 51 36272892
2024 Rare genetic variation in fibronectin 1 (FN1) protects against APOEε4 in Alzheimer's disease. Acta neuropathologica 47 38598053
2019 Let's cross-link: diverse functions of the promiscuous cellular transglutaminase factor XIII-A. Journal of thrombosis and haemostasis : JTH 47 30489000
2012 Let's make it happen: the role of let-7 microRNA in development. Current topics in developmental biology 47 22365733
2019 The LncRNA LINC00963 facilitates osteosarcoma proliferation and invasion by suppressing miR-204-3p/FN1 axis. Cancer biology & therapy 46 30975024
2003 Regulation of p53 functions: let's meet at the nuclear bodies. Current opinion in cell biology 46 12787779
2004 The LetE protein enhances expression of multiple LetA/LetS-dependent transmission traits by Legionella pneumophila. Infection and immunity 44 15155631
2018 Downregulation of NEAT1 reverses the radioactive iodine resistance of papillary thyroid carcinoma cell via miR-101-3p/FN1/PI3K-AKT signaling pathway. Cell cycle (Georgetown, Tex.) 43 30596336
2020 Let's talk about sex in the context of COVID-19. Journal of applied physiology (Bethesda, Md. : 1985) 40 32437244
2021 Let's get physical - mechanisms of crossover interference. Journal of cell science 39 34037217
2020 Let's Talk About Sex-Biological Sex Is Underreported in Biomaterial Studies. Advanced healthcare materials 36 33043626
2020 Acute e-cig inhalation impacts vascular health: a study in smoking naïve subjects. American journal of physiology. Heart and circulatory physiology 36 33216614
2019 Knockdown of IRE1ɑ suppresses metastatic potential of colon cancer cells through inhibiting FN1-Src/FAK-GTPases signaling. The international journal of biochemistry & cell biology 35 31326465
2022 Let's Get Physical: Flavivirus-Host Protein-Protein Interactions in Replication and Pathogenesis. Frontiers in microbiology 33 35308381
2021 LINC02381 aggravates breast cancer through the miR-1271-5p/FN1 axis to activate PI3K/AKT pathway. Molecular carcinogenesis 32 34882856
1977 Synthesis, secretion, and attachment of LETS glycoprotein in normal and transformed cells. Journal of supramolecular structure 32 616487
2022 FN1 encoding fibronectin as a pivotal signaling gene for therapeutic intervention against pancreatic cancer. Molecular genetics and genomics : MGG 31 35982245
2022 High FN1 expression correlates with gastric cancer progression. Pathology, research and practice 30 36274380
2011 Accurate description of the cell survival and biological effect at low and high doses and LET's. Journal of radiation research 30 21785229
2023 FN1 mRNA 3'-UTR supersedes traditional fibronectin 1 in facilitating the invasion and metastasis of gastric cancer through the FN1 3'-UTR-let-7i-5p-THBS1 axis. Theranostics 28 37771777
2010 The Legionella pneumophila LetA/LetS two-component system exhibits rheostat-like behavior. Infection and immunity 27 20351136
2022 HOXA13 promotes gastric cancer progression partially via the FN1-mediated FAK/Src axis. Experimental hematology & oncology 25 35197128
2020 Long non-coding RNA DBH-AS1 promotes cancer progression in diffuse large B-cell lymphoma by targeting FN1 via RNA-binding protein BUD13. Cell biology international 25 32091157
2018 LET's sponge: How the lncRNA PFL promotes cardiac fibrosis. Theranostics 25 29463987
2016 Meningococcal Biofilm Formation: Let's Stick Together. Trends in microbiology 25 27712951
2005 Genetic mechanisms specifying cortical connectivity: let's make some projections together. Neuron 25 15882638
2024 Let's make it personal: CRISPR tools in manipulating cell death pathways for cancer treatment. Cell biology and toxicology 24 39075259
2023 RNA Sequencing Reveals Novel Oncogenic Fusions and Depicts Detailed Fusion Transcripts of FN1-FGFR1 in Phosphaturic Mesenchymal Tumors. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 24 37391169
2021 Upregulation of CCT3 promotes cervical cancer progression through FN1. Molecular medicine reports 24 34651664
2017 FN1, FOS, and ITGA5 induce preeclampsia: Abnormal expression and methylation. Hypertension in pregnancy 24 29039998
2020 The effect and clinical significance of FN1 expression on biological functions of gastric cancer cells. Cellular and molecular biology (Noisy-le-Grand, France) 23 33040835
2020 E-cig might cause cell damage of oral mucosa. Oral surgery, oral medicine, oral pathology and oral radiology 23 33610539
2023 FN1 mediated activation of aspartate metabolism promotes the progression of triple-negative and luminal a breast cancer. Breast cancer research and treatment 22 37458908
2023 Unravelling the role of immune cells and FN1 in the recurrence and therapeutic process of skull base chordoma. Clinical and translational medicine 22 37784253
2022 Let's talk about (biological) sex. Nature reviews. Molecular cell biology 22 35197611
2017 A novel microRNA-1207-3p/FNDC1/FN1/AR regulatory pathway in prostate cancer. RNA & disease (Houston, Tex.) 22 28251177
2023 MicroRNA-142-3P suppresses the progression of papillary thyroid carcinoma by targeting FN1 and inactivating FAK/ERK/PI3K signaling. Cellular signalling 20 37406787
2019 Role of FN1 and GREB1 gene polymorphisms in endometriosis. Molecular medicine reports 20 31115525
1978 Microfilament bundles, LETS protein and growth control in somatic cell hybrids. Journal of cell science 19 363730
2024 Mitochondrial remodeling underlying age-induced skeletal muscle wasting: let's talk about sex. Free radical biology & medicine 18 38574975
2023 FN1 Promotes Thyroid Carcinoma Cell Proliferation and Metastasis by Activating the NF-Κb Pathway. Protein and peptide letters 18 36278453
2023 FN1 and cancer-associated fibroblasts markers influence immune microenvironment in clear cell renal cell carcinoma. The journal of gene medicine 18 37358013
2022 Let's talk about sex: A biological variable in immune response against melanoma. Pigment cell & melanoma research 18 35076986
2020 MicroRNA-219c-5p regulates bladder fibrosis by targeting FN1. BMC urology 18 33287818
2024 Circular RNA hsa_circ_0050386 suppresses non-small cell lung cancer progression via regulating the SRSF3/FN1 axis. Journal of translational medicine 17 38216996
2022 Dopamine systems and biological rhythms: Let's get a move on. Frontiers in integrative neuroscience 17 35965599
2020 How do immune and mesenchymal cells influence the intestinal epithelial cell compartment in inflammatory bowel disease? Let's crosstalk about it! Journal of leukocyte biology 17 32057139
2023 Integration of transcriptomics and metabolomics reveals a novel gene signature guided by FN1 associated with immune response in oral squamous cell carcinoma tumorigenesis. Journal of cancer research and clinical oncology 16 36656379
2020 GRN, NOTCH3, FN1, and PINK1 expression in eutopic endometrium - potential biomarkers in the detection of endometriosis - a pilot study. Journal of assisted reproduction and genetics 16 33029756
2019 Aberrant expressions of miRNA-206 target, FN1, in multifactorial Hirschsprung disease. Orphanet journal of rare diseases 16 30616633
2011 Melanoma-associated genes, MXI1, FN1, and NME1, are hypoxia responsive in murine and human melanoma cells. Melanoma research 16 21912348
2008 A novel report of cig-FISH and cytogenetics in POEMS syndrome. American journal of hematology 16 18839437
2024 Single-cell RNA sequencing identifies a subtype of FN1 + tumor-associated macrophages associated with glioma recurrence and as a biomarker for immunotherapy. Biomarker research 15 39375795
2022 Impact of E-cig aerosol vaping on fetal and neonatal respiratory development and function. Translational research : the journal of laboratory and clinical medicine 15 35351623
2021 E-cig vapor condensate alters proteome and lipid profiles of membrane rafts: impact on inflammatory responses in A549 cells. Cell biology and toxicology 15 33469865
2019 Differential expression of extracellular matrix‑related genes DCN, EPHA4, FN1, SPARC, SPON2 and SPP1 in colorectal carcinogenesis. Oncology reports 15 31524274
2010 Let's get physical: gamete interaction in flowering plants. Biochemical Society transactions 15 20298235
2023 FN1 and TGFBI are key biomarkers of macrophage immune injury in diabetic kidney disease. Medicine 14 37960829
2022 Let's shape again: the concerted molecular action that builds the pollen tube. Plant reproduction 14 35041045
2022 GATA6‑induced FN1 activation promotes the proliferation, invasion and migration of oral squamous cell carcinoma cells. Molecular medicine reports 14 35088888
2022 LncRNA-HOTAIR Inhibits H9c2 Apoptosis After Acute Myocardial Infarction via miR-206/FN1 Axis. Biochemical genetics 14 35092560
2017 miR-206 inhibits FN1 expression and proliferation and promotes apoptosis of rat type II alveolar epithelial cells. Experimental and therapeutic medicine 14 28587394
2022 Bioinformatics and Machine Learning Methods to Identify FN1 as a Novel Biomarker of Aortic Valve Calcification. Frontiers in cardiovascular medicine 13 35295271
2024 Enhancing Vasculogenesis in Dental Pulp Development: DPSCs-ECs Communication via FN1-ITGA5 Signaling. Stem cell reviews and reports 12 38418738
2021 PTPRM methylation induced by FN1 promotes the development of glioblastoma by activating STAT3 signalling. Pharmaceutical biology 12 34225581
2025 Targeting PRDX2 to inhibit tumor growth and metastasis in triple-negative breast cancer: the role of FN1 and the PI3K/AKT/SP1 pathway. Journal of translational medicine 11 40217291
2024 YY1 mediated DCUN1D5 transcriptional activation promotes triple-negative breast cancer progression by targeting FN1/PI3K/AKT pathway. Biology direct 11 38831379
2023 Anti-Liver Fibrosis Role of miRNA-96-5p via Targeting FN1 and Inhibiting ECM-Receptor Interaction Pathway. Applied biochemistry and biotechnology 11 36943602
2016 Genetic aberrations in multiple myeloma characterized by cIg-FISH: a Brazilian context. Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas 11 27074166
2003 Synapse formation: let's stick together. Current biology : CB 11 12526761
2023 A high-impact FN1 variant correlates with fibronectin-mediated glomerulopathy via decreased binding to collagen type IV. Pathology 10 36774238
2022 [Soft tissue tumours with FN1 (Fibronectin 1) fusion gene]. Annales de pathologie 10 35181149
2022 Schwann cell‑like cells derived from human amniotic mesenchymal stem cells promote sciatic nerve repair through an exosome‑induced SOX2/FN1 pathway in vitro. International journal of molecular medicine 10 35475578
2022 Hsa_circ_0000285 contributes to gastric cancer progression by upregulating FN1 through the inhibition of miR-1278. Journal of clinical laboratory analysis 10 35535385
2025 FN1 from cancer-associated fibroblasts orchestrates pancreatic cancer metastasis via integrin-PI3K/AKT signaling. Frontiers in oncology 9 40678072
2024 Circular RNA Gtdc1 Protects Against Offspring Osteoarthritis Induced by Prenatal Prednisone Exposure by Regulating SRSF1-Fn1 Signaling. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 9 38520084

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