Affinage

FAP

Prolyl endopeptidase FAP · UniProt Q12884

Length
760 aa
Mass
87.7 kDa
Annotated
2026-06-09
100 papers in source corpus 22 papers cited in narrative 22 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

FAP is a type II transmembrane serine protease with both dipeptidyl peptidase and post-proline endopeptidase activities that processes extracellular substrates to regulate fibrosis, metabolism, cardiac repair, and tumor immunosuppression (PMID:9688278, PMID:27689014). Homodimerization through a small-X3-small transmembrane motif (G10, S14, A18) is required for both cell-surface trafficking and endopeptidase activity (PMID:27155568). Enzymatically, FAP cleaves and inactivates the metabolic hormone FGF21 at a specific post-proline site (PMID:27689014, PMID:28970566), degrades BNP in cardiac fibroblasts to restrain post-infarct angiogenesis (PMID:36756875), and mediates ordered proteolysis of MMP-derived collagen fragments to promote their internalization via Endo180 and limit fibrosis (PMID:26663085). In the tumor and inflammatory stroma, FAP-expressing cancer-associated fibroblasts and macrophages drive immunosuppression: a uPAR-FAK-Src-JAK2 pathway sustains STAT3 activation and CCL2 production to recruit myeloid-derived suppressor cells (PMID:27216177, PMID:31759251), FN1-integrin α5β1-FAK-AKT-STAT3 signaling polarizes macrophages toward an M2 phenotype (PMID:40263422), and adipose-tissue macrophage FAP drives CCL8-dependent proinflammatory recruitment and modulates lipolysis (PMID:38100414). Independently of its catalytic activity, FAP recruits PRKDC into lipid rafts to activate NF-κB and promote ovarian cancer cell survival (PMID:36494579). FAP expression is itself induced by STAT3 binding to its promoter downstream of IL-17a in hepatic stellate cells (PMID:38740736). Distinct from this transmembrane protease, the FAP-1/PTPN13 protein tyrosine phosphatase—which shares the FAP alias—binds the C-terminal 15 residues of Fas to suppress Fas surface export and apoptosis (PMID:7536343, PMID:12724420) and antagonizes IGF-I/IRS-1/PI3K/Akt survival signaling (PMID:12354757).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 1995 High

    Established the FAP-1/PTPN13 phosphatase as a direct Fas-binding inhibitor of apoptosis, defining the minimal interaction surface on Fas.

    Evidence Yeast two-hybrid, co-IP, deletion mapping, and overexpression rescue in T cells

    PMID:7536343

    Open questions at the time
    • Did not establish the structural basis of the interaction
    • Mechanism of apoptosis suppression downstream of binding undefined
    • This protein is distinct from the FAP transmembrane protease sharing the alias
  2. 1998 High

    Defined FAP (the transmembrane protease) biochemically as a DPP IV-homologous serine protease with dipeptidyl peptidase activity.

    Evidence Baculovirus expression of chimeric FAP and in vitro dipeptidyl peptidase assay plus genomic structure analysis

    PMID:9688278

    Open questions at the time
    • No physiological substrate identified
    • Endopeptidase activity not yet distinguished from dipeptidyl peptidase activity
  3. 1999 Medium

    Confirmed FAP-1 functions as an endogenous inhibitor of Fas-mediated apoptosis in primary thyrocytes via its Fas-binding motif.

    Evidence Competitive Ac-SLV tripeptide inhibition and cycloheximide synergy in primary thyroid follicular cells

    PMID:10537175

    Open questions at the time
    • No direct mutagenesis
    • Phosphatase catalytic contribution not dissected
  4. 2003 High

    Mechanistically linked FAP-1 binding to retention of Fas in an intracellular cytoskeletal pool, explaining apoptosis suppression by limiting surface Fas.

    Evidence Overexpression, dominant-negative, siRNA, and Fas site-directed mutagenesis with surface Fas flow cytometry

    PMID:12724420

    Open questions at the time
    • Trafficking machinery coupling FAP-1 to Fas retention unresolved
    • Generality across cell types not established
  5. 2002 High

    Identified a Fas-independent pro-apoptotic role for FAP-1 through inhibition of IGF-I/IRS-1/PI3K/Akt survival signaling in breast cancer cells.

    Evidence Antisense knockdown with PI3K activity, Akt phosphorylation, and IRS-1 phosphorylation readouts in MCF7

    PMID:12354757

    Open questions at the time
    • Direct phosphatase substrate within the pathway not pinpointed
    • Cross-talk with the Fas pathway unaddressed
  6. 2015 High

    Placed FAP protease in collagen catabolism, showing it processes MMP-derived fragments to enable Endo180-mediated internalization and prevent fibrosis.

    Evidence FAP-KO mice in fibrosis models, in vitro collagen cleavage, internalization assay, and AAV rescue

    PMID:26663085

    Open questions at the time
    • Precise cleavage sites on collagen fragments not mapped
    • Coordination with Endo180 at the molecular level unclear
  7. 2016 High

    Identified FGF21 as a physiological FAP endopeptidase substrate, establishing FAP as the enzyme that inactivates this metabolic hormone in vivo.

    Evidence Talabostat inhibition in DIO mice with FGF21-KO epistasis and in vitro FGF21 degradation

    PMID:27689014

    Open questions at the time
    • Tissue source of FGF21-cleaving FAP not localized
    • Relationship to FAP dimerization-dependent activity not tested here
  8. 2016 High

    Showed FAP-expressing fibroblasts drive tumor immunosuppression through a uPAR-FAK-Src-JAK2-STAT3 axis producing CCL2 to recruit MDSCs.

    Evidence Enforced FAP expression, pathway inhibitors, STAT3/CCL2 readouts, and Ccr2-KO validation in a murine liver tumor model

    PMID:27216177

    Open questions at the time
    • Whether protease activity is required for this signaling not resolved
    • Upstream trigger of uPAR engagement undefined
  9. 2016 High

    Demonstrated that transmembrane dimerization via a G10/S14/A18 motif is required for FAP trafficking and endopeptidase activity, coupling assembly to function.

    Evidence AraTM dimerization assay, TM interface mutagenesis, and enzymatic/localization readouts

    PMID:27155568

    Open questions at the time
    • Structural model of the dimer not solved
    • Effect of dimerization on substrate selectivity untested
  10. 2017 High

    Refined FAP substrate specificity, showing circulating FAP cleaves FGF21 at a defined post-proline site distinct from PREP and DPPIV, and built a clinical activity assay.

    Evidence Fluorescence FGF21-cleavage assay, structural modeling, Fap-KO validation, and human cirrhosis plasma

    PMID:28970566

    Open questions at the time
    • Structure-function model not experimentally validated by crystallography
    • Disease causality of elevated FAP activity not established
  11. 2018 Medium

    Resolved FAP+ stroma into immunosuppressive FAP+PDPN+ CAFs and non-suppressive FAP+PDPN- pericytes, attributing T cell suppression to a nitric oxide mechanism.

    Evidence Flow cytometry, RNA-seq of sorted populations, immunofluorescence, and T cell proliferation assays with NO inhibition

    PMID:30266714

    Open questions at the time
    • Role of FAP enzymatic activity in NO-mediated suppression not tested
    • Single tumor type
  12. 2019 Medium

    Extended the FAP-STAT3-CCL2-MDSC axis to cholangiocarcinoma CAFs, confirming MDSC-dependence by CCL2 rescue and Gr-1 depletion.

    Evidence FAP knockdown in primary ICC-CAFs, CCL2 ELISA, MDSC migration, and in vivo Gr-1 depletion with CCL2 rescue

    PMID:31759251

    Open questions at the time
    • Upstream regulator of fibroblastic FAP not identified here
    • Single lab
  13. 2022 Medium

    Revealed a catalysis-independent FAP function: recruiting PRKDC into lipid rafts to activate NF-κB and BIRC5-mediated survival in ovarian cancer.

    Evidence siRNA silencing, FAP-PRKDC co-IP, lipid raft fractionation, enzymatic mutants, and aptamer-delivered siRNA xenografts

    PMID:36494579

    Open questions at the time
    • Single Co-IP for the FAP-PRKDC interaction
    • How a transmembrane protease scaffolds PRKDC mechanistically unclear
  14. 2022 High

    Established macrophage FAP as a driver of obesity, acting through CCL8-dependent macrophage recruitment and monoamine oxidase suppression to modulate lipolysis.

    Evidence Macrophage-specific Fap-KO on HFD, CCL8 overexpression rescue, MAO/NE/energy expenditure assays

    PMID:38100414

    Open questions at the time
    • Substrate underlying CCL8 induction not identified
    • Link to FAP protease activity not dissected
  15. 2023 High

    Identified BNP as a cardiac FAP substrate whose degradation limits angiogenesis, with FAP inhibition improving post-MI cardiac function.

    Evidence Fap-KO and pharmacological inhibition in MI mice with Nppb-KO and Npr1-KO epistasis and endothelial co-culture

    PMID:36756875

    Open questions at the time
    • Precise BNP cleavage product responsible not defined
    • Cellular source of active FAP in infarct zone not localized
  16. 2024 Medium

    Showed FAP transcription is directly driven by STAT3 downstream of IL-17a in hepatic stellate cells, linking inflammatory signaling to FAP induction in HCC.

    Evidence CUT&RUN for STAT3 at the FAP promoter plus IL-17a/FAP overexpression and in vivo HCC models

    PMID:38740736

    Open questions at the time
    • Whether FAP enzymatic activity mediates the tumor effect not tested
    • Single lab
  17. 2024 Medium

    Implicated FAP+ chondrocytes in osteoarthritis, with FAP driving NF-κB-dependent senescence and soluble FAP degrading type II collagen.

    Evidence Chondrocyte-specific FAP-KO OA model, OE/KD, SA-β-Gal, NF-κB analysis, and FAPI PET imaging

    PMID:39456041

    Open questions at the time
    • Catalytic vs scaffold contribution to senescence not separated
    • Single lab
  18. 2024 Medium

    Extended FAP's inflammatory role to periodontitis, where senescent fibroblast FAP drives macrophage inflammation and bone resorption via mTOR-linked FAP/osteolectin imbalance.

    Evidence scRNA-seq, recombinant FAP on macrophages, rapamycin, and FAP inhibition in mouse periodontitis

    PMID:39716898

    Open questions at the time
    • Direct FAP substrate in this context not identified
    • Single lab
  19. 2025 Medium

    Defined a FAP+ CAF secretome mechanism, FN1-integrin α5β1-FAK-AKT-STAT3, driving M2 macrophage polarization and immunosuppression in breast cancer.

    Evidence scRNA-seq, signaling analysis, integrin blocking, and Cilengitide inhibition in mouse models

    PMID:40263422

    Open questions at the time
    • Role of FAP catalytic activity in FN1 production unclear
    • Single lab
  20. 2024 Medium

    Linked FAP+ gastric stromal cells to tumor progression through INHBA-SMAD2/3 paracrine signaling and collagen-ITGB1-FAK-YAP mechanotransduction.

    Evidence FAP+ cell isolation, conditioned medium, INHBA ELISA, SMAD2/3 blots, and integrin/FAK/YAP analysis

    PMID:39615112

    Open questions at the time
    • Direct role of FAP enzyme in INHBA secretion not established
    • Single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved when FAP's diverse stromal and metabolic phenotypes depend on its protease catalysis versus non-enzymatic scaffolding, and no structural model of the FAP dimer or substrate complexes has been experimentally determined.
  • No crystal structure of FAP or its substrate complexes in the corpus
  • Catalysis-dependent vs scaffold functions not systematically separated across contexts
  • Substrates underlying chemokine induction (CCL2, CCL8) not identified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 5 GO:0016787 hydrolase activity 4 GO:0140097 catalytic activity, acting on DNA 1
Localization
GO:0005856 cytoskeleton 2 GO:0005634 nucleus 1 GO:0005886 plasma membrane 1
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-168256 Immune System 4 R-HSA-5357801 Programmed Cell Death 4 R-HSA-1430728 Metabolism 2 R-HSA-1474244 Extracellular matrix organization 1
Partners
FASFGF21FN1ITGA5ITGB1MPRIPPRKDC

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 FAP-1 (PTPN13), a protein tyrosine phosphatase, was identified as a binding partner of Fas (CD95/Apo-1); the carboxyl-terminal 15 amino acids of Fas are necessary and sufficient for interaction with FAP-1. Gene transfer-mediated overexpression of FAP-1 partially abolished Fas-induced apoptosis in a T cell line, establishing FAP-1 as an inhibitor of Fas-mediated apoptosis. Yeast two-hybrid screen, co-immunoprecipitation, deletion mapping, gene transfer overexpression assay in T cells Science High 7536343
2003 FAP-1 association with Fas attenuates Fas export to the cell surface, increasing the intracellular pool of Fas within the cytoskeleton network. Forced FAP-1 expression reduced surface Fas; dominant-negative FAP-1 or FAP-1 siRNA knockdown upregulated surface Fas. A point mutation at amino acid 275 of Fas decreased FAP-1 association and increased Fas surface export. Overexpression of FAP-1 and dominant-negative FAP-1, siRNA knockdown, flow cytometry for surface Fas, site-directed mutagenesis of Fas Molecular and cellular biology High 12724420
2002 PTPL1/FAP-1 phosphatase triggers apoptosis in human breast cancer cells (MCF7) via inhibition of the insulin receptor substrate-1/PI3K/Akt pathway, independent of Fas. FAP-1 expression abolished IGF-I-induced survival signaling (80% reduction in PI3K activity, 55% inhibition of Akt activation, 65% decrease in IRS-1 phosphorylation). Antisense transfection to abolish PTPL1/FAP-1, TUNEL and nucleosome ELISA for apoptosis, PI3K activity assay, Akt phosphorylation assay, IRS-1 tyrosine phosphorylation assay The Journal of biological chemistry High 12354757
1998 Mouse FAP (Fap) encodes a serine protease with dipeptidyl peptidase activity, consistent with its homology to dipeptidyl peptidase IV (DPP IV). A chimeric FAP fusion protein expressed in a baculovirus system demonstrated dipeptidyl peptidase activity. The gene spans ~60 kb with 26 exons; the serine protease consensus motif WGWSYGG is split across two exons, a feature shared with DPP IV. Baculovirus expression of chimeric FAP fusion protein, enzymatic dipeptidyl peptidase activity assay, genomic structure analysis European journal of biochemistry High 9688278
2016 FAP triggers induction of a cancer-associated fibroblast (CAF) subset with an inflammatory phenotype through a uPAR-dependent FAK-Src-JAK2 signaling pathway that persistently activates STAT3, leading to upregulation of CCL2. FAP(+)CAF-derived CCL2 promotes tumor growth by recruiting myeloid-derived suppressor cells (MDSCs) via CCR2. Abrogation of this effect in Ccr2-deficient mice confirmed the pathway. Enforced FAP expression in normal fibroblasts, signaling pathway inhibition (uPAR, FAK, Src, JAK2), STAT3 activation assays, CCL2 measurement, MDSC recruitment assay in murine liver tumor model, Ccr2-knockout mice Cancer research High 27216177
2015 FAP participates in collagen catabolism by mediating ordered proteolytic processing of matrix metalloproteinase (MMP)-derived collagen cleavage products, leading to increased collagen internalization via Endo180 without altering Endo180 expression. FAP-deficient mice showed accumulation of intermediate-sized collagen fragments and increased lung fibrosis; restoration of FAP expression in FAP-deficient mouse lungs reduced lung hydroxyproline to wild-type levels. FAP-knockout mice in bleomycin and irradiation fibrosis models, in vitro collagen cleavage assay, pharmacologic FAP inhibition, collagen internalization assay, AAV-mediated FAP re-expression in FAP-deficient mice The Journal of biological chemistry High 26663085
2016 Pharmacological inhibition of FAP (using talabostat) in diet-induced obese mice elevated total and intact plasma FGF21 levels and produced robust metabolic benefits (reduced body weight, improved glucose tolerance, reduced adiposity). These effects were absent in FGF21-knockout obese mice, and FAP inhibition in vitro blocked enzymatic degradation of human FGF21. This establishes FAP as the endopeptidase responsible for FGF21 cleavage/inactivation in vivo. Pharmacologic inhibition with talabostat in DIO mice, FGF21-KO mice as controls, in vitro FAP enzymatic assay with human FGF21, intact FGF21 measurement by ELISA Molecular metabolism High 27689014
2017 A fluorescence-based assay established that circulating FAP endopeptidase cleaves FGF21 at a specific post-proline site, distinguishing FAP endopeptidase activity from related enzymes (PREP, DPPIV). Structural modeling elucidated the mechanistic basis for FAP substrate specificity. Assay was validated using Fap-deficient mice and detected elevated FAP activity in human patients with liver cirrhosis. Homogeneous fluorescence intensity assay with FGF21 as substrate, Fap-KO mice validation, structural modeling, human plasma samples from liver cirrhosis patients Scientific reports High 28970566
2023 FAP (Fap) is a prolyl-specific serine protease that degrades BNP (brain natriuretic peptide), a novel substrate identified in cardiac fibroblasts. Fap degrades BNP to inhibit vascular endothelial cell migration and tube formation. Pharmacological or genetic inhibition of Fap in mice improved cardiac function after myocardial infarction and increased angiogenesis in the peri-infarct zone. Cardioprotective effects of FAP inhibition were absent in Nppb (pre-proBNP)- or Npr1 (BNP receptor)-deficient mice, confirming BNP as the physiological substrate mediating these effects. Fap-KO and pharmacological inhibition in MI mouse model, echocardiography, RNA-seq, biochemical analysis, cardiac fibroblast/endothelial cell co-culture, Nppb-KO and Npr1-KO epistasis experiments Circulation research High 36756875
2016 Specific residues (G10, S14, A18) in the FAP transmembrane domain form a small-X3-small motif that mediates FAP homodimerization. Mutations to these interfacial residues (G10L, S14L, A18L) reduced FAP TM-CYTO dimerization. G10L specifically decreased FAP endopeptidase activity by more than 25% and reduced cell-surface versus intracellular FAP expression, establishing that TM-mediated dimerization is required for both FAP trafficking and protease activity. AraTM bacterial dimerization assay, site-directed mutagenesis of TM interface residues, FAP endopeptidase activity assay, cell surface vs. intracellular FAP localization Biochimica et biophysica acta High 27155568
1999 FAP-1 (PTPN13) is functionally expressed in human thyrocytes and protects them from Fas-mediated programmed cell death. Competitive inhibition of FAP-1 binding to Fas using synthetic Ac-SLV tripeptide significantly increased Fas-mediated cell death, and synergized with sub-optimal cycloheximide treatment, demonstrating FAP-1 functions as an endogenous inhibitor of Fas-induced apoptosis in thyroid follicular cells. Ribonuclease protection assay for FAP-1 mRNA, immunohistochemistry and flow cytometry for FAP-1 protein, competitive inhibition with Ac-SLV tripeptide, cycloheximide treatment, cell death assay Endocrinology Medium 10537175
2022 FAP expression in adipose tissue macrophages (ATM) mediates CCL8 chemokine expression, which recruits monocyte-derived proinflammatory macrophages into obese adipose tissue. Macrophage-specific FAP deficiency protected mice from diet-induced obesity and reduced proinflammatory macrophage infiltration. FAP in ATM also decreases monoamine oxidase expression, thereby increasing norepinephrine levels and enhancing lipolysis in white adipose tissue. CCL8 overexpression restored HFD-induced metabolic phenotypes in FAP-deficient mice. Macrophage-specific Fap-knockout mice on high-fat diet, CCL8 measurement, CCL8 overexpression rescue experiment, monoamine oxidase assay, NE measurement, energy expenditure assay Proceedings of the National Academy of Sciences of the United States of America High 38100414
2022 FAP in ovarian cancer cells recruits PRKDC (DNA-PK) into lipid rafts, enabling NF-κB activation and promoting cell survival via BIRC5 (survivin) downstream. FAP depletion prevented lipid raft localization of PRKDC and abolished NF-κB activity. FAP's enzymatic activity was dispensable for this pro-survival function, as established by enzymatic mutant analysis. FAP silencing by siRNA, NF-κB activity assay, co-immunoprecipitation of FAP and PRKDC, lipid raft fractionation, apoptosis assay, enzymatic activity mutants, EpCAM aptamer-delivered FAP siRNA in xenograft Cancer gene therapy Medium 36494579
2019 Fibroblastic FAP expression is required for STAT3 activation and CCL2 production in intrahepatic cholangiocarcinoma cancer-associated fibroblasts. FAP knockdown in ICC-CAFs impaired their ability to promote ICC growth, MDSCs infiltration and angiogenesis; these effects were restored by exogenous CCL2. The tumor-promoting function of fibroblastic FAP was dependent on MDSCs, as depletion of Gr-1+ cells reversed the restoring effects of CCL2. FAP knockdown in primary ICC-CAFs, CCL2 ELISA, MDSC migration assay, subcutaneous tumor model with Gr-1 depletion, exogenous CCL2 rescue Neoplasia Medium 31759251
2018 In breast tumors, FAP+ stromal cells comprise two distinct populations distinguished by podoplanin (PDPN) expression: FAP+PDPN+ cancer-associated fibroblasts (CAFs) enriched in TGFβ signaling/fibrosis genes and localized at the tumor outer edge in contact with T cells, and FAP+PDPN- cancer-associated pericytes (CAPs) localized around vessels. FAP+PDPN+ CAFs suppressed T cell proliferation via a nitric oxide-dependent mechanism, whereas FAP+PDPN- pericytes were not immunosuppressive. Flow cytometry, RNA sequencing of sorted cell populations, immunofluorescence for localization, T cell proliferation assay with nitric oxide pathway inhibition Cancer immunology research Medium 30266714
2011 FAP-1 (PTPN13) shows differentiation-dependent relocalization in pancreatic adenocarcinoma A818-6 cells: in 2D monolayers, FAP-1 localizes to a juxtanuclear cisternal position and the nucleus; upon 3D differentiation into polarized hollow spheres, FAP-1 relocates to the actin cytoskeleton beneath the outer plasma membrane and co-localizes with CD95 (Fas). Knockdown of FAP-1 mRNA in monolayer cells did not alter responsiveness to CD95 agonistic antibodies, indicating that FAP-1 expression did not affect CD95 signal transduction in this context. Immunofluorescence for FAP-1 and CD95 localization in 2D vs. 3D cultures, flow cytometry for surface CD95, FAP-1 siRNA knockdown, caspase activity assay Differentiation; research in biological diversity Medium 22364882
2024 IL-17a promotes hepatocellular carcinoma by increasing FAP expression in hepatic stellate cells (HSCs) via activation of the STAT3 signaling pathway. STAT3 directly binds to the FAP promoter region (confirmed by CUT&RUN), regulating FAP transcription. Overexpression of IL-17a and FAP in HSCs promoted HCC cell proliferation and migration and inhibited HCC cell apoptosis in vitro and in vivo. CUT&RUN assay for STAT3 binding to FAP promoter, IL-17a and FAP overexpression in HSCs, in vivo tumor models, HCC cell proliferation/migration/apoptosis assays Cell death discovery Medium 38740736
2023 FAP overexpression in colorectal cancer cells promoted cell growth, invasion, metastasis, and enhanced chemoresistance. MPRIP (myosin phosphatase Rho-interacting protein) was identified as a direct interacting protein of FAP. FAP influences chemotherapy resistance and macrophage recruitment/M2 polarization through the Rho/Hippo/YAP signaling pathway. Co-immunoprecipitation for FAP-MPRIP interaction, FAP overexpression and knockdown in CRC cells, invasion/migration assays, macrophage polarization assay, YAP signaling analysis iScience Low 37213233
2024 FAP-positive chondrocytes in osteoarthritis promote chondrocyte senescence; overexpression of FAP in chondrocytes promotes senescence while genetic knockout of FAP in chondrocytes alleviates OA. FAP siRNA knockdown suppressed the NF-κB pathway to reduce the senescence-associated secretory phenotype (SASP). Soluble FAP secreted from OA synovium was shown to degrade type II collagen in cartilage. FAP overexpression and siRNA knockdown in chondrocytes, chondrocyte-specific FAP-KO mouse OA model, SA-β-Gal senescence assay, NF-κB pathway analysis, PET/CT with [68Ga]Ga-FAPI-04, LNP-FAP siRNA intraarticular injection in rat OA model Journal of nanobiotechnology Medium 39456041
2024 FAP in senescent gingival fibroblasts promotes periodontitis via FAP/OLN (osteolectin) imbalance driven by mTOR pathway activation. Recombinant FAP increased pro-inflammatory cytokine secretion and osteoclast differentiation in macrophages. Rapamycin treatment restored the FAP/OLN balance. FAP inhibition reduced macrophage inflammation, collagen degradation, and bone resorption in experimental periodontitis. scRNA-seq, recombinant FAP treatment of macrophages, rapamycin treatment of gingival fibroblasts, FAP inhibition in mouse periodontitis model, osteoclast differentiation assay, cytokine measurement Advanced science Medium 39716898
2025 FAP+ cancer-associated fibroblasts in breast cancer secrete fibronectin 1 (FN1), which engages integrin α5β1 on macrophages to activate FAK-AKT-STAT3 signaling and drive immunosuppressive M2-like macrophage polarization. Pharmacological disruption of FN1-integrin α5β1 signaling with Cilengitide reprogrammed the tumor immune landscape and suppressed tumor growth in mouse models. scRNA-seq, Co-IP/signaling pathway analysis, Cilengitide pharmacological inhibition in vivo mouse models, macrophage polarization assay, integrin α5β1 blocking experiments Oncogene Medium 40263422
2024 FAP+ gastric cancer mesenchymal stromal cells promote gastric cancer progression by paracrine secretion of INHBA, which activates SMAD2/3 signaling in GC cells. FAP+ GCMSCs also induce collagen deposition in ECM that upregulates GC cell invasion and stemness through collagen–ITGB1 interaction triggering FAK and YAP phosphorylation. FAP+ cell isolation by flow cytometry, transcriptomic sequencing, conditioned medium experiments, ELISA for INHBA, Western blot for SMAD2/3 phosphorylation, IHC and Masson trichrome staining for ECM, integrin/FAK/YAP pathway analysis International immunopharmacology Medium 39615112

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2013 Targeting CXCL12 from FAP-expressing carcinoma-associated fibroblasts synergizes with anti-PD-L1 immunotherapy in pancreatic cancer. Proceedings of the National Academy of Sciences of the United States of America 1677 24277834
1991 Mutations of chromosome 5q21 genes in FAP and colorectal cancer patients. Science (New York, N.Y.) 1671 1651563
2022 Single-cell and spatial analysis reveal interaction of FAP+ fibroblasts and SPP1+ macrophages in colorectal cancer. Nature communications 716 35365629
1995 FAP-1: a protein tyrosine phosphatase that associates with Fas. Science (New York, N.Y.) 668 7536343
2016 FAP Promotes Immunosuppression by Cancer-Associated Fibroblasts in the Tumor Microenvironment via STAT3-CCL2 Signaling. Cancer research 612 27216177
2014 Understanding fibroblast activation protein (FAP): substrates, activities, expression and targeting for cancer therapy. Proteomics. Clinical applications 392 24470260
1994 Familial adenomatous polyposis (FAP): frequency, penetrance, and mutation rate. Human mutation 340 8199592
2006 Correlations between mutation site in APC and phenotype of familial adenomatous polyposis (FAP): a review of the literature. Critical reviews in oncology/hematology 258 17064931
2022 Preclinical evaluation of FAP-2286 for fibroblast activation protein targeted radionuclide imaging and therapy. European journal of nuclear medicine and molecular imaging 217 35608703
2016 Sixty years of transthyretin familial amyloid polyneuropathy (TTR-FAP) in Europe: where are we now? A European network approach to defining the epidemiology and management patterns for TTR-FAP. Current opinion in neurology 174 26734951
2018 FAP Delineates Heterogeneous and Functionally Divergent Stromal Cells in Immune-Excluded Breast Tumors. Cancer immunology research 160 30266714
2021 Fibroblast Activation Protein (FAP)-Targeted CAR-T Cells: Launching an Attack on Tumor Stroma. ImmunoTargets and therapy 135 34386436
2021 FAP and FAPI-PET/CT in Malignant and Non-Malignant Diseases: A Perfect Symbiosis? Cancers 123 34638433
2021 Simlukafusp alfa (FAP-IL2v) immunocytokine is a versatile combination partner for cancer immunotherapy. mAbs 105 33974508
2015 Fibroblast Activation Protein (FAP) Accelerates Collagen Degradation and Clearance from Lungs in Mice. The Journal of biological chemistry 100 26663085
2020 OMTX705, a Novel FAP-Targeting ADC Demonstrates Activity in Chemotherapy and Pembrolizumab-Resistant Solid Tumor Models. Clinical cancer research : an official journal of the American Association for Cancer Research 95 32161121
2003 FAP-1 association with Fas (Apo-1) inhibits Fas expression on the cell surface. Molecular and cellular biology 88 12724420
2021 Translational imaging of the fibroblast activation protein (FAP) using the new ligand [68Ga]Ga-OncoFAP-DOTAGA. European journal of nuclear medicine and molecular imaging 83 34957527
2023 Targeting fibroblast activation protein (FAP): advances in CAR-T cell, antibody, and vaccine in cancer immunotherapy. Drug delivery and translational research 81 36840906
2020 High Expression of FAP in Colorectal Cancer Is Associated With Angiogenesis and Immunoregulation Processes. Frontiers in oncology 77 32733792
2019 Fibroblastic FAP promotes intrahepatic cholangiocarcinoma growth via MDSCs recruitment. Neoplasia (New York, N.Y.) 75 31759251
2021 Radioligands Targeting Fibroblast Activation Protein (FAP). Cancers 71 34830898
2006 The genetics of FAP and FAP-like syndromes. Familial cancer 71 16998667
2016 Fibroblast activation protein (FAP) as a novel metabolic target. Molecular metabolism 69 27689014
2023 Inhibition of Fap Promotes Cardiac Repair by Stabilizing BNP. Circulation research 63 36756875
2022 A Dimeric FAP-Targeting Small-Molecule Radioconjugate with High and Prolonged Tumor Uptake. Journal of nuclear medicine : official publication, Society of Nuclear Medicine 57 35589404
2002 Protein-tyrosine phosphatase PTPL1/FAP-1 triggers apoptosis in human breast cancer cells. The Journal of biological chemistry 56 12354757
1998 Mouse fibroblast-activation protein--conserved Fap gene organization and biochemical function as a serine protease. European journal of biochemistry 56 9688278
2024 Antitumor efficacy and potential mechanism of FAP-targeted radioligand therapy combined with immune checkpoint blockade. Signal transduction and targeted therapy 53 38825657
2014 FAP neuropathy and emerging treatments. Current neurology and neuroscience reports 52 24482069
2017 Gastric tumours in FAP. Familial cancer 51 28271232
2023 TGF-β1 dominates stromal fibroblast-mediated EMT via the FAP/VCAN axis in bladder cancer cells. Journal of translational medicine 49 37461061
2021 Fibroblast Activation Protein (FAP) targeting homodimeric FAP inhibitor radiotheranostics: a step to improve tumor uptake and retention time. American journal of nuclear medicine and molecular imaging 49 35003886
2006 Fibroblast activation protein (FAP) is upregulated in myelomatous bone and supports myeloma cell survival. British journal of haematology 47 16512833
2022 Monitoring Therapeutic Response to Anti-FAP CAR T Cells Using [18F]AlF-FAPI-74. Clinical cancer research : an official journal of the American Association for Cancer Research 45 35972732
2024 Bispecific CAR-T cells targeting FAP and GPC3 have the potential to treat hepatocellular carcinoma. Molecular therapy. Oncology 44 38882528
2024 TWIST1+FAP+ fibroblasts in the pathogenesis of intestinal fibrosis in Crohn's disease. The Journal of clinical investigation 44 39024569
2020 Characterization and oncolytic virus targeting of FAP-expressing tumor-associated pericytes in glioblastoma. Acta neuropathologica communications 43 33308315
2021 Clinical results of fibroblast activation protein (FAP) specific PET for non-malignant indications: systematic review. EJNMMI research 41 33606104
2024 DAB2 + macrophages support FAP + fibroblasts in shaping tumor barrier and inducing poor clinical outcomes in liver cancer. Theranostics 40 39239526
2021 Preparation and Bioevaluation of 99mTc-Labeled FAP Inhibitors as Tumor Radiotracers to Target the Fibroblast Activation Protein. Molecular pharmaceutics 40 34904839
2022 Hetero-bivalent agents targeting FAP and PSMA. European journal of nuclear medicine and molecular imaging 38 35965291
2020 Clinical Results of Fibroblast Activation Protein (FAP) Specific PET and Implications for Radiotherapy Planning: Systematic Review. Cancers 38 32942573
2022 Design, Synthesis and Preclinical Assessment of 99mTc-iFAP for In Vivo Fibroblast Activation Protein (FAP) Imaging. Molecules (Basel, Switzerland) 37 35011496
2005 Liver transplantation and new therapeutic approaches for familial amyloidotic polyneuropathy (FAP). Medical molecular morphology 36 16170462
2017 Selective Homogeneous Assay for Circulating Endopeptidase Fibroblast Activation Protein (FAP). Scientific reports 34 28970566
2024 Preclinical Development of PNT6555, a Boronic Acid-Based, Fibroblast Activation Protein-α (FAP)-Targeted Radiotheranostic for Imaging and Treatment of FAP-Positive Tumors. Journal of nuclear medicine : official publication, Society of Nuclear Medicine 31 38050111
2020 Altered expression of fibroblast activation protein-α (FAP) in colorectal adenoma-carcinoma sequence and in lymph node and liver metastases. Aging 31 32428869
2020 Altered Tissue and Plasma Levels of Fibroblast Activation Protein-α (FAP) in Renal Tumours. Cancers 31 33207686
2015 Bispecific single-chain diabody-immunoliposomes targeting endoglin (CD105) and fibroblast activation protein (FAP) simultaneously. Journal of controlled release : official journal of the Controlled Release Society 30 25617725
2023 FAP, CD10, and GPR77-labeled CAFs cause neoadjuvant chemotherapy resistance by inducing EMT and CSC in gastric cancer. BMC cancer 29 37277751
2025 In vivo FAP-CAR macrophages enhance chemotherapy and immunotherapy against pancreatic cancer by removing the fibrosis barrier. Journal of controlled release : official journal of the Controlled Release Society 28 40425095
2012 Genotype--phenotype correlation in FAP. Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis 28 22620962
2023 FAP expression in adipose tissue macrophages promotes obesity and metabolic inflammation. Proceedings of the National Academy of Sciences of the United States of America 26 38100414
2022 Radiosynthesis and Preclinical Evaluation of Bispecific PSMA/FAP Heterodimers for Tumor Imaging. Pharmaceuticals (Basel, Switzerland) 26 35337180
1999 Characterization of FAP-1 expression and function in thyroid follicular cells. Endocrinology 26 10537175
2025 Dissecting FAP+ Cell Diversity in Pancreatic Cancer Uncovers an Interferon-Response Subtype of Cancer-Associated Fibroblasts with Tumor-Restraining Properties. Cancer research 25 40215177
2024 Preclinical Evaluation of 177Lu-OncoFAP-23, a Multivalent FAP-Targeted Radiopharmaceutical Therapeutic for Solid Tumors. Journal of nuclear medicine : official publication, Society of Nuclear Medicine 25 39266289
2013 Expression of FAP, ADAM12, WISP1, and SOX11 is heterogeneous in aggressive fibromatosis and spatially relates to the histologic features of tumor activity. Cancer medicine 25 24402778
2005 Mutation spectrum of the APC gene in 83 Korean FAP families. Human mutation 25 16088911
2024 Initial Experience with 68Ga-FAP-2286 PET Imaging in Patients with Urothelial Cancer. Journal of nuclear medicine : official publication, Society of Nuclear Medicine 24 38212070
2022 Could Fibroblast Activation Protein (FAP)-Specific Radioligands Be Considered as Pan-Tumor Agents? Contrast media & molecular imaging 24 35280710
2022 Photodynamic therapy-improved oncolytic bacterial immunotherapy with FAP-encoding S. typhimurium. Journal of controlled release : official journal of the Controlled Release Society 24 36181917
2021 Oncogenesis, Microenvironment Modulation and Clinical Potentiality of FAP in Glioblastoma: Lessons Learned from Other Solid Tumors. Cells 23 34068501
2016 A specific, transmembrane interface regulates fibroblast activation protein (FAP) homodimerization, trafficking and exopeptidase activity. Biochimica et biophysica acta 22 27155568
2023 Development and Characterization of Novel FAP-Targeted Theranostic Pairs: A Bench-to-Bedside Study. Research (Washington, D.C.) 20 38706713
2011 The genetics of familial adenomatous polyposis (FAP) and MutYH-associated polyposis (MAP). Acta gastro-enterologica Belgica 20 22103048
2024 Targeting FAP-positive chondrocytes in osteoarthritis: a novel lipid nanoparticle siRNA approach to mitigate cartilage degeneration. Journal of nanobiotechnology 19 39456041
2024 Senescent Fibroblasts Drive FAP/OLN Imbalance Through mTOR Signaling to Exacerbate Inflammation and Bone Resorption in Periodontitis. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 19 39716898
2020 Discovery of a novel fibroblast activation protein (FAP) inhibitor, BR103354, with anti-diabetic and anti-steatotic effects. Scientific reports 19 33277568
2023 FAP-targeted PET imaging in gastrointestinal malignancies: a comprehensive review. Cancer imaging : the official publication of the International Cancer Imaging Society 17 37608378
2020 Protein Proximity Observed Using Fluorogen Activating Protein and Dye Activated by Proximal Anchoring (FAP-DAPA) System. ACS chemical biology 17 32786268
2024 Circulating soluble fibroblast activation protein (FAP) levels are independent of cardiac and extra-cardiac FAP expression determined by targeted molecular imaging in patients with myocardial FAP activation. International journal of cardiology 16 38614364
2025 Single-cell and spatial transcriptomics profile the interaction of SPP1 macrophages and FAP fibroblasts in non-small cell lung cancer. Translational lung cancer research 15 40799444
2024 SPP1+ macrophages and FAP+ fibroblasts promote the progression of pMMR gastric cancer. Scientific reports 15 39482333
2023 FAP promotes metastasis and chemoresistance via regulating YAP1 and macrophages in mucinous colorectal adenocarcinoma. iScience 15 37213233
2023 FAP-retargeted Ad5 enables in vivo gene delivery to stromal cells in the tumor microenvironment. Molecular therapy : the journal of the American Society of Gene Therapy 15 37641405
2025 FAP-targeted delivery of radioiodinated probes: A progressive albumin-driven strategy for tumor theranostics. Journal of controlled release : official journal of the Controlled Release Society 14 40180251
2024 IL-17a promotes hepatocellular carcinoma by increasing FAP expression in hepatic stellate cells via activation of the STAT3 signaling pathway. Cell death discovery 14 38740736
2023 A multifactorial analysis of FAP to regulate gastrointestinal cancers progression. Frontiers in immunology 14 37325617
2011 Characterisation of FAP-1 expression and CD95 mediated apoptosis in the A818-6 pancreatic adenocarcinoma differentiation system. Differentiation; research in biological diversity 14 22364882
2023 Tumor-Targeted Interleukin 2 Boosts the Anticancer Activity of FAP-Directed Radioligand Therapeutics. Journal of nuclear medicine : official publication, Society of Nuclear Medicine 13 37734838
2019 FAP-a and GOLPH3 Are Hallmarks of DCIS Progression to Invasive Breast Cancer. Frontiers in oncology 13 31921678
2017 Human microRNA expression in sporadic and FAP-associated desmoid tumors and correlation with beta-catenin mutations. Oncotarget 13 28418912
2025 Fibroblast Activation Protein (FAP)+ cancer-associated fibroblasts induce macrophage M2-like polarization via the Fibronectin 1-Integrin α5β1 axis in breast cancer. Oncogene 12 40263422
2023 Identifying the oncogenic roles of FAP in human cancers based on systematic analysis. Aging 12 37490719
2022 FAP-α+ immunofibroblasts in oral lichen planus promote CD4+ T-cell infiltration via CCL5 secretion. Experimental dermatology 12 35598279
2022 Expression of GLUT4 and FAP in urothelial bladder carcinoma: correlation with angiogenesis and clinicopathological characteristics. Journal of the Egyptian National Cancer Institute 12 36155866
2016 FAP finds FGF21 easy to digest. The Biochemical journal 11 27118870
2025 Intercellular communication between FAP+ fibroblasts and SPP1+ macrophages in prostate cancer via multi-omics. Frontiers in immunology 10 40438108
2024 Diagnostic yield of FAP-guided positron emission tomography in thyroid cancer: a systematic review. Frontiers in medicine 10 38590320
2024 FAP Radioligand Linker Optimization Improves Tumor Dose and Tumor-to-Healthy Organ Ratios in 4T1 Syngeneic Model. Journal of medicinal chemistry 10 39013156
2023 Functional roles of FAP-α in metabolism, migration and invasion of human cancer cells. Frontiers in oncology 10 36937451
2022 FAP is critical for ovarian cancer cell survival by sustaining NF-κB activation through recruitment of PRKDC in lipid rafts. Cancer gene therapy 10 36494579
2022 Stromal FAP Expression is Associated with MRI Visibility and Patient Survival in Prostate Cancer. Cancer research communications 10 36874403
2021 Identification of BR102910 as a selective fibroblast activation protein (FAP) inhibitor. Bioorganic & medicinal chemistry letters 10 33571650
2025 FAP+ activated fibroblasts are detectable in the microenvironment of endometriosis and correlate with stroma composition and infiltrating CD8+ and CD68+ cells. Human reproduction open 9 39959762
2024 FAP+ gastric cancer mesenchymal stromal cells via paracrining INHBA and remodeling ECM promote tumor progression. International immunopharmacology 9 39615112
2020 A cell-based fluorescent assay for FAP inhibitor discovery. Bioorganic & medicinal chemistry letters 9 32527554
2016 Expression of the FAP gene in non-fibroblast human cell lines. Development of cancer-associated fibroblast models. Doklady. Biochemistry and biophysics 9 27817025

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