Affinage

FASN

Fatty acid synthase · UniProt P49327

Length
2511 aa
Mass
273.4 kDa
Annotated
2026-06-09
100 papers in source corpus 30 papers cited in narrative 30 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

FASN is the multifunctional enzyme that drives de novo fatty acid synthesis, with inhibitors binding its ketoacyl reductase domain as uncompetitive inhibitors toward NADPH (PMID:39999714); through this lipogenic output it couples cellular metabolism to signaling, immunity, and oncogenesis. Its transcription is activated combinatorially: FBI-1/ZBTB7A synergizes with SREBP-1 and Sp1 at the proximal promoter (PMID:18682402), TAF15 directly occupies and activates the promoter to drive hepatic steatosis (PMID:37183512), and the PKM2-SREBP-1c and AKT/mTOR axes feed into the same promoter program (PMID:34619345, PMID:30221356), while AhR activation downregulates FASN transcription (PMID:40557796). At the protein level FASN abundance is set by a balance of E3 ligases that drive K48-ubiquitination and degradation — FBXW7β (countered by CSN6) (PMID:37202390) and TRIM21 (PMID:37249651) — opposed by deubiquitinases USP13 (PMID:35898882) and VCP-recruited USP2 (PMID:39489738), and by palmitoylation, with ZDHHC20 palmitoylating FASN at C1471/C1881 to block SNX8-TRIM28 ubiquitination and stabilize it (PMID:39696259), while ZDHHC21 palmitoylates C1317 to destabilize it (PMID:38195819). The palmitate FASN produces is itself a signaling substrate: it supplies palmitoylation of MYD88 at C113 to enable IRAK4 recruitment and TLR signaling (PMID:31427815), palmitoylates MHC-I to target it for lysosomal degradation via DHHC3 (PMID:38486485), palmitoylates PD-L1 to support immune evasion (PMID:39349429), and palmitoylates mutant p53 to block its ubiquitination and sustain gain-of-function oncogenic activity (PMID:39971971); FASN-derived malonyl-CoA conversely suppresses STING palmitoylation (PMID:38878833). Beyond metabolism, FASN-dependent lipogenesis is required for radial glia polarity and cortical brain development (PMID:34996870), alveolar type II cell surfactant phospholipid homeostasis (PMID:37606038), and autophagosome-lysosome fusion through interaction with the SNARE components STX17, SNAP29 and VAMP8 (PMID:38164137). FASN inhibition elevates BH3-only proteins and shifts cancer cells toward BCL-2-dependent apoptotic priming (PMID:34675185) and rewires metabolism toward IDH1-driven reductive carboxylation (PMID:37578864).

Mechanistic history

Synthesis pass · year-by-year structured walk · 28 steps
  1. 2008 High

    Established how FASN transcription is combinatorially controlled, showing that the oncoprotein FBI-1/ZBTB7A cooperates with the master lipogenic factor SREBP-1 rather than acting alone.

    Evidence Promoter luciferase reporters, EMSA/ChIP-type DNA binding, and FBI-1/SREBP-1/Sp1 co-transfection

    PMID:18682402

    Open questions at the time
    • Does not address protein-level regulation of FASN
    • Tissue context of FBI-1 synergy not defined
  2. 2015 Medium

    Showed that extracellular hormonal signaling (TSH/TSHR) feeds into FASN expression via PKA and ERK1/2, linking endocrine input to adipocyte lipogenesis.

    Evidence TSH treatment of mature adipocytes with selective PKA/ERK/JNK inhibitors

    PMID:25655684

    Open questions at the time
    • Transcription factor target downstream of ERK/PKA not identified
    • Single cell-type system
  3. 2018 Medium

    Connected glycolytic enzyme PKM2 to FASN regulation through SREBP-1c and AKT/mTOR, illustrating cross-talk between glucose and lipid metabolism programs.

    Evidence Co-IP of PKM2-SREBP-1c, PKM2 knockdown, AKT/mTOR inhibitors in bladder cancer cells

    PMID:30221356

    Open questions at the time
    • Whether PKM2-SREBP-1c interaction is direct on the FASN promoter not shown
    • Single lab
  4. 2019 High

    Defined FASN's lipid product as a signaling currency by showing FASN-derived saturated fatty acids supply MYD88 palmitoylation required for IRAK4 binding and TLR signaling.

    Evidence FASN inhibition (C75), ZDHHC6 knockdown, MYD88 C113 mutagenesis, IRAK4-MYD88 Co-IP, sepsis models

    PMID:31427815

    Open questions at the time
    • Does not address other palmitoylation substrates
    • Quantitative flux from FASN to MYD88 palmitate not measured
  5. 2020 High

    Linked a specific FASN variant to neural pathology, showing a knock-in R1819W/R1812W allele causes lipid accumulation and ER stress that impair neural progenitor proliferation and cognition.

    Evidence FASN R1812W knock-in mice, R1819W hESC forebrain organoids, lipid profiling, ER stress markers, behavior

    PMID:32386572

    Open questions at the time
    • Enzymatic consequence of R1819W on FASN catalysis not resolved
    • No human disease cohort linkage in this entry
  6. 2021 High

    Explained why FASN inhibition kills cancer cells by showing it raises BH3-only proteins and apoptotic priming, creating BCL-2 dependence exploitable by venetoclax/navitoclax.

    Evidence FASN inhibitors, BIM/PUMA loss-of-function epistasis, BH3 profiling, breast cancer xenografts

    PMID:34675185

    Open questions at the time
    • Precise redox trigger (palmitate vs NADPH) for BH3 induction not isolated
  7. 2021 Medium

    Revealed a feedback loop in which FASN levels control mTOR malonylation at K1218 and mTORC1 activity, which in turn regulates FASN transcription via SREBP-1.

    Evidence DHA treatment, FASN siRNA, mTOR K1218 mutagenesis, malonylation assays, SREBP-1 ChIP at FASN promoter

    PMID:34619345

    Open questions at the time
    • Whether malonyl-CoA directly malonylates mTOR or via an enzyme unresolved
    • Generalizability beyond retinal endothelium unknown
  8. 2022 High

    Established FASN-dependent lipogenesis as essential for cortical development by demonstrating that brain-specific Fasn loss disrupts radial glia polarity and causes microcephaly.

    Evidence Conditional Fasn KO (Emx1Cre) mice and pharmacological inhibition in human forebrain organoids

    PMID:34996870

    Open questions at the time
    • Lipid species mediating polarity not identified
    • Molecular link from lipogenesis to apical polarity machinery undefined
  9. 2022 Medium

    Identified deubiquitination as a FASN stabilizing mechanism, showing USP13's catalytic activity is required to sustain FASN and cancer stem cell properties.

    Evidence USP13-FASN Co-IP, catalytically inactive USP13 mutant rescue, SCLC xenografts

    PMID:35898882

    Open questions at the time
    • Ubiquitin chain linkage removed by USP13 not characterized
    • Single lab
  10. 2023 High

    Defined the FBXW7β degradation axis and its CSN6 antagonism, establishing how FASN is degraded and how that degradation is blocked in colorectal cancer.

    Evidence Reciprocal Co-IP, ubiquitination assays, FBXW7β mutants, CSN6 manipulation, PDX models

    PMID:37202390

    Open questions at the time
    • FBXW7β degron on FASN not mapped
    • Generality across tissues not tested
  11. 2023 High

    Identified TRIM21 as a K48-ubiquitin ligase for FASN that limits hepatic lipid accumulation, connecting FASN turnover to metabolic disease.

    Evidence Co-IP, K48-ubiquitination assays, TRIM21 manipulation in diabetic mice with FASN rescue

    PMID:37249651

    Open questions at the time
    • FASN residues ubiquitinated by TRIM21 not defined
    • Crosstalk with FBXW7β pathway not addressed
  12. 2023 Medium

    Implicated FABP5 as a negative regulator of FASN via ubiquitin-proteasome degradation, coupling FASN loss to mTOR suppression/autophagy and Wnt/β-catenin signaling across two cancer types.

    Evidence FABP5-FASN Co-IP, ubiquitination assays, FABP5 manipulation, orlistat rescue in CRC and pNEN models

    PMID:37302809 PMID:37416772

    Open questions at the time
    • Whether FABP5 recruits a specific E3 ligase unknown
    • Direct binding interface not mapped
  13. 2023 Medium

    Showed FASN protein is regulated by competing PTMs beyond ubiquitination, with CircRREB1 blocking acetylation-dependent ubiquitination and inducing RanBP2-mediated SUMOylation to stabilize FASN.

    Evidence CircRREB1 manipulation, ubiquitination/acetylation/SUMOylation assays, intra-articular adenovirus in mice

    PMID:37640697

    Open questions at the time
    • FASN SUMO and acetylation sites not pinpointed
    • Mechanism centers on the circRNA rather than direct FASN biochemistry
  14. 2023 High

    Revealed a metabolic adaptation to FASN loss, showing FASN-deficient cells use IDH1 reductive carboxylation and mitochondrial citrate transport to resist detachment-induced oxidative stress.

    Evidence Stable-isotope metabolic flux analysis with IDH1/CTP epistasis in spheroids

    PMID:37578864

    Open questions at the time
    • Whether this adaptation drives FASN-inhibitor resistance in vivo not established
  15. 2023 High

    Identified TAF15 as a direct FASN promoter activator promoting steatosis, while also acting through NF-κB independently of FASN.

    Evidence CUT&TAG, dual-luciferase reporter, TAF15-p65 Co-IP, hepatocyte-specific AAV manipulation, NASH models, FASN inhibitor rescue

    PMID:37183512

    Open questions at the time
    • TAF15 binding motif on FASN promoter not defined
    • Relationship to SREBP-1 occupancy unclear
  16. 2023 Medium

    Connected FASN downregulation to differentiation, showing FASN knockdown drives TFEB nuclear translocation and lysosomal biogenesis to accelerate granulocytic differentiation in leukemia.

    Evidence RNAi FASN knockdown, EGCG treatment, TFEB translocation and CLEAR gene assays in APL cells

    PMID:33742137

    Open questions at the time
    • Mechanistic link from FASN to TFEB activation not defined
    • Single lab
  17. 2024 High

    Defined opposing palmitoyltransferases that set FASN stability, with ZDHHC20 (C1471/C1881) blocking ubiquitination to stabilize FASN and ZDHHC21 (C1317) destabilizing it.

    Evidence ABE/LC-MS palmitoylation mapping, Co-IP, ubiquitination and half-life assays, site mutagenesis, ZDHHC20 KO mice; ZDHHC21 Co-IP/mutagenesis in DLBCL

    PMID:38195819 PMID:39696259

    Open questions at the time
    • How a single enzyme family produces opposite stability outcomes mechanistically unresolved
    • Context-dependence of ZDHHC choice unclear
  18. 2024 High

    Showed FASN-supplied palmitate controls antigen presentation, with FASN inhibition reducing MHC-I palmitoylation and DHHC3-mediated lysosomal degradation to boost surface MHC-I and T-cell killing.

    Evidence CRISPR FASN KO, FASN inhibitors, DHHC3-MHC-I Co-IP, palmitoylation assays, CD8 cytotoxicity, orthotopic model

    PMID:38486485

    Open questions at the time
    • Direct flux from FASN palmitate to MHC-I acylation not isotope-traced
  19. 2024 Medium

    Extended FASN palmitate signaling to immune checkpoint control, showing FASN depletion abolishes PD-L1 palmitoylation and induction, sensitizing cancer cells to T-cell killing.

    Evidence CRISPR FASN KO, PD-L1 palmitoylation assays, real-time T-cell cytotoxicity, ETC analysis

    PMID:39349429

    Open questions at the time
    • No in vivo validation in this study
    • Palmitoyltransferase for PD-L1 not identified here
  20. 2024 High

    Showed FASN palmitate stabilizes mutant p53, defining a route by which lipogenesis sustains gain-of-function oncogenic p53.

    Evidence FASN-mutp53 Co-IP, palmitoylation/ubiquitination assays, FASN inhibition across xenografts, transgenic mice, organoids

    PMID:39971971

    Open questions at the time
    • mutp53 palmitoylation site not mapped in this entry
    • Whether wild-type p53 is similarly affected unaddressed
  21. 2024 Medium

    Demonstrated FASN-derived malonyl-CoA negatively regulates innate immunity by inhibiting STING palmitoylation at C91, distinguishing malonyl-CoA from palmitate as a regulatory metabolite.

    Evidence Metabolomics, STING-KO mice, FASN inhibitors, STING C91 mutagenesis

    PMID:38878833

    Open questions at the time
    • Mechanism by which malonyl-CoA inhibits a palmitoyltransferase not resolved
    • Single lab
  22. 2024 Medium

    Added VCP/USP2 as a FASN-stabilizing deubiquitination module that promotes autophagy and osteosarcoma progression, with the interaction interfaces mapped.

    Evidence Co-IP/MS, K48-ubiquitination assays, docking, truncation mapping, LC3/TEM autophagy readouts, xenografts

    PMID:39489738

    Open questions at the time
    • FASN deubiquitination site not defined
    • Single lab
  23. 2024 Medium

    Linked FASN to ferroptosis and radioresistance via a GSTM3-USP14 axis that stabilizes FASN to sustain lipid synthesis.

    Evidence Co-IP/MS, ferroptosis markers, in vitro and xenograft radiosensitivity assays

    PMID:38228715

    Open questions at the time
    • Direct USP14-FASN deubiquitination not biochemically isolated from GSTM3-GPX4 effects
    • Single lab
  24. 2024 Medium

    Connected gut-microbial AhR signaling to FASN transcription, showing AhR activation lowers FASN and shifts the MUFA/PUFA ratio to sensitize cells to ferroptosis.

    Evidence AhR activation, FASN knockdown, lipid profiling, ferroptosis assays in vitro and in vivo

    PMID:40557796

    Open questions at the time
    • Direct AhR occupancy of FASN promoter inferred not demonstrated
    • Single lab
  25. 2024 Low

    Implicated DPP3 in FASN protein stabilization to support breast cancer lipogenesis, though the mechanism of stabilization remains undefined.

    Evidence DPP3 KO, GSEA, FASN Western blot, free fatty acid metabolomics

    PMID:38655619

    Open questions at the time
    • No direct DPP3-FASN binding or ubiquitination assay reported
    • Stabilization inferred from KO plus Western blot only
    • Single lab
  26. 2024 Medium

    Identified a non-metabolic structural role for FASN in late autophagy, showing FASN interacts with the SNARE machinery and is required for autophagosome-lysosome fusion.

    Evidence Co-IP/immunofluorescence of FASN with STX17/SNAP29/VAMP8, rescue, autophagy markers, TEM

    PMID:38164137

    Open questions at the time
    • Whether FASN catalysis or scaffolding mediates fusion not separated
    • Direct binding interface not mapped
  27. 2024 Medium

    Defined FASN's surfactant role, showing AEC2-specific Fasn deletion alters surfactant phospholipid composition and raises surface tension, worsening smoke-induced lung injury.

    Evidence AEC2-specific Fasn KO, BALF lipidomics, surface tension assay, lung histology

    PMID:37606038

    Open questions at the time
    • Specific FASN-derived phospholipid precursor not identified
    • Single lab
  28. 2025 Medium

    Resolved the binding mode of clinical FASN inhibitors, showing TVB-3166/TVB-3664 act as uncompetitive inhibitors at the ketoacyl reductase domain toward NADPH, with NADPH accumulation tracking apoptotic sensitivity.

    Evidence Computational docking/kinetics, NADPH accumulation assays, BH3 profiling, PDX combination experiments

    PMID:39999714

    Open questions at the time
    • Binding mode is largely computational
    • Crystallographic confirmation absent

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the many FASN regulatory inputs — opposing palmitoyltransferases, multiple E3 ligases/DUBs, and transcriptional activators — are integrated in a given cell, and whether FASN's palmitate-donor, malonyl-CoA, and SNARE-scaffolding roles are catalytically separable, remains unresolved.
  • No unified quantitative model of FASN protein-level regulation
  • Flux tracing from FASN to specific substrate palmitoylation events lacking
  • Scaffold vs catalytic contributions of FASN to autophagy not dissected

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 3 GO:0016491 oxidoreductase activity 1 GO:0140097 catalytic activity, acting on DNA 1
Localization
GO:0005829 cytosol 2
Pathway
R-HSA-168256 Immune System 4 R-HSA-1430728 Metabolism 3 R-HSA-392499 Metabolism of proteins 3 R-HSA-74160 Gene expression (Transcription) 2 R-HSA-9612973 Autophagy 2 R-HSA-1266738 Developmental Biology 1 R-HSA-5357801 Programmed Cell Death 1
Partners
FABP5FBXW7STX17TRIM21USP13USP2ZDHHC20ZDHHC21

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2019 FASN-derived saturated fatty acids supply palmitoylation of MYD88 at cysteine 113 via the palmitoyltransferase ZDHHC6; this palmitoylation is required for IRAK4 binding to the MYD88 intermediate domain and downstream TLR/MYD88 signal activation. Pharmacological FASN inhibition (C75), ZDHHC6 knockdown, site-directed mutagenesis of MYD88 C113, co-immunoprecipitation of IRAK4–MYD88, in vivo sepsis models Nature chemical biology High 31427815
2024 FASN inhibition reduces palmitoylation of MHC-I, preventing its lysosomal degradation and thereby increasing MHC-I surface levels and antigen presentation; the palmitoyltransferase DHHC3 directly binds MHC-I and negatively regulates its protein levels. Genetic FASN KO (CRISPR/Cas9), pharmacological FASN inhibitors (orlistat, TVB-2640), Co-IP of DHHC3–MHC-I, palmitoylation assays, CD8+ T-cell cytotoxicity assays, orthotopic mouse model Cancer research High 38486485
2024 ZDHHC20 palmitoylates FASN at cysteines 1471 and 1881, competing with the E3 ubiquitin ligase complex SNX8-TRIM28-mediated ubiquitination; ZDHHC20-mediated palmitoylation stabilizes FASN protein and promotes hepatocarcinogenesis. Palmitoylation LC-MS, acyl-biotin exchange assay, Co-IP, ubiquitination assays, protein half-life assays, ZDHHC20 knockout mice with chemical HCC induction Molecular cancer High 39696259
2024 ZDHHC21 palmitoylates FASN at Cys1317, destabilizing FASN protein and reducing fatty acid synthesis; loss of ZDHHC21 in DLBCL increases FASN stability and promotes tumor cell proliferation. Co-IP of ZDHHC21–FASN, palmitoylation assays, site-directed mutagenesis (C1317), in vitro and in vivo DLBCL proliferation assays Leukemia High 38195819
2025 FASN interacts with mutant p53 (mutp53) and promotes its palmitoylation, which inhibits mutp53 ubiquitination, stabilizes mutp53 protein, and supports gain-of-function oncogenic activity; pharmacological or genetic FASN inhibition suppresses mutp53 palmitoylation and tumor growth. Co-IP of FASN–mutp53, palmitoylation assays, FASN genetic inhibition and small-molecule inhibitors, orthotopic/subcutaneous xenograft models, transgenic mice, human tumor organoids Nature communications High 39971971
2023 FBXW7β, a cytoplasmic FBXW7 isoform, functions as an E3 ubiquitin ligase for FASN, targeting it for degradation; COP9 signalosome subunit 6 (CSN6) associates with both FBXW7β and FASN, promotes FBXW7β autoubiquitination and degradation, thereby preventing FASN ubiquitination and stabilizing FASN to sustain lipogenesis in colorectal cancer. Co-IP, ubiquitination assays, FBXW7β mutation analysis, CSN6 overexpression/knockdown, patient-derived xenograft experiments Signal transduction and targeted therapy High 37202390
2023 TRIM21 promotes K48-linked ubiquitination and proteasomal degradation of FASN through direct protein–protein interaction, thereby reducing hepatic lipid accumulation and improving metabolic phenotypes in diabetic mice. Co-IP, ubiquitination (K48-linkage) assays, TRIM21 overexpression/knockdown in obese diabetic mice, rescue with FASN overexpression Cellular and molecular life sciences High 37249651
2023 FABP5 interacts with FASN and activates the ubiquitin-proteasome pathway to decrease FASN protein levels, suppressing lipid accumulation and mTOR signaling to promote autophagy in colorectal cancer cells. Co-IP of FABP5–FASN, ubiquitination assays, FABP5 overexpression/knockdown, in vitro and in vivo functional assays International journal of biological sciences Medium 37416772
2022 Deletion of Fasn specifically in mouse embryonic telencephalon (Emx1Cre) causes severe microcephaly due to altered polarity of apical radial glia progenitors and reduced progenitor proliferation; pharmacological FASN inhibition in human forebrain organoids recapitulates the radial glia polarity defect, establishing FASN-dependent de novo lipogenesis as required for cortical brain development. Conditional Fasn KO (Emx1Cre), pharmacological inhibition in hESC-derived forebrain organoids, immunofluorescence and proliferation assays Proceedings of the National Academy of Sciences of the United States of America High 34996870
2020 Neural stem/progenitor cells (NSPCs) expressing a FASN R1819W (mouse R1812W) variant display FASN-dependent lipid accumulation and ER stress that impairs NSPC proliferation; homozygous mice show reduced adult hippocampal NSPC activity and cognitive defects. Knock-in mouse model (FASN R1812W), hESC lines with FASN R1819W, 3D forebrain organoids, lipid profiling, ER stress markers, behavioral testing Cell stem cell High 32386572
2021 FASN inhibition elevates pro-apoptotic BH3-only proteins BIM, PUMA, and NOXA; the resulting redox imbalance (palmitate/NADPH-related) heightens mitochondrial apoptotic priming, shifting cancer cells toward BCL-2 dependence and synergizing with BCL-2/BCL-XL inhibitors (navitoclax, venetoclax) to induce cell death. Pharmacological FASN inhibitors, BIM/PUMA loss-of-function experiments, BH3 profiling, BCL-2 family protein Western blots, breast cancer xenograft models with oral FASNi Cell death & disease High 34675185
2024 FASN-produced malonyl-CoA inhibits STING palmitoylation (at C91) in macrophages; FASN inhibition reduces available malonyl-CoA and palmitate, thereby suppressing STING pathway activation and alleviating sepsis-induced liver injury. Metabolomics, STING-KO mice, FASN inhibitor screening, palmitoylation assays, C91 mutagenesis of STING Biochimica et biophysica acta. Molecular basis of disease Medium 38878833
2024 FASN depletion prevents adaptive PD-L1 induction by interferon-gamma and reduces constitutive PD-L1 overexpression by abolishing PD-L1 post-translational palmitoylation; FASN-deficient cancer cells show enhanced susceptibility to cytokine-activated T-cell killing and suppressed mitochondrial OXPHOS. CRISPR/Cas9 FASN KO cell lines, real-time T-cell cytotoxicity assays, PD-L1 palmitoylation assays, electron transport chain complex analysis, mathematical modeling Cell death discovery Medium 39349429
2008 FBI-1 (ZBTB7A/Pokemon) synergistically activates FASN gene transcription with SREBP-1 by binding the proximal GC-box and SRE/E-box elements of the FASN promoter; FBI-1 alters the binding pattern of Sp1 and SREBP-1 on these elements to drive enhanced transcriptional activation. Luciferase promoter reporter assays, DNA-protein binding assays (EMSA/ChIP-type), co-transfection of FBI-1, SREBP-1, and Sp1 The Journal of biological chemistry High 18682402
2023 TAF15 binds directly to the FASN promoter and activates its transcription, promoting hepatic steatosis; TAF15 also interacts with p65 (NF-κB) to activate inflammatory signaling independently of FASN. CUT&TAG chromatin profiling, dual-luciferase reporter assay, Co-IP of TAF15–p65, AAV-mediated hepatocyte-specific TAF15 KD/OE, NASH mouse models, FASN inhibitor rescue Liver international High 37183512
2022 USP13 deubiquitinase interacts with FASN and enhances FASN protein stability; the enzymatic activity of USP13 is required for this stabilization and for maintenance of SCLC cancer stem cell properties and de novo fatty acid synthesis. Co-IP of USP13–FASN, enzyme-inactive USP13 mutant rescue experiments, FASN/USP13 KD in SCLC lines and xenografts Frontiers in oncology Medium 35898882
2024 VCP recruits the deubiquitinase USP2 to remove K48-linked ubiquitin chains from FASN, stabilizing FASN protein; domain 2 of VCP and a specific USP2 sequence are critical for their interaction; the VCP/USP2/FASN axis activates autophagy and promotes osteosarcoma progression. Co-IP combined with mass spectrometry, K48-ubiquitination assays, molecular docking, protein truncation mapping, LC3 fluorescence confocal, TEM, in vivo xenograft Cell death & disease Medium 39489738
2024 GSTM3 stabilizes the deubiquitinase USP14, which in turn inhibits ubiquitination and degradation of FASN; elevated FASN sustains lipid synthesis that suppresses radiation-induced ferroptosis in NPC cells, while GSTM3 also independently interacts with and suppresses GPX4. Co-IP, mass spectrometry, immunofluorescence co-localization, ferroptosis markers, in vitro and xenograft radiosensitivity assays British journal of cancer Medium 38228715
2023 CircRREB1 inhibits acetylation-dependent ubiquitination of FASN (preventing proteasomal degradation) and simultaneously induces RanBP2-mediated SUMOylation of FASN to enhance its protein stability, thereby supporting senescence-associated lipid dysregulation in chondrocytes. CircRREB1 knockdown/overexpression, ubiquitination assays, acetylation assays, SUMOylation assays, intra-articular injection of adenovirus-CircRreb1 in mice Nature communications Medium 37640697
2023 FASN deficiency induces reductive carboxylation by IDH1 that generates cytosolic citrate; this citrate is exported back to mitochondria via the mitochondrial citrate transport protein (CTP), conferring resistance to detachment-induced oxidative stress in anchorage-independent cancer cells. Metabolic flux analysis (MFA) with stable isotope tracing, IDH1 and CTP genetic inhibition in FASN-deficient cells, oxidative stress assays in spheroids Cell reports High 37578864
2024 FASN interacts with SNARE complex components STX17, SNAP29, and VAMP8, and FASN activity is required for autophagosome-lysosome fusion; FASN inhibition (via AMPK activator MK8722) blocks late-stage autophagy by disrupting this FASN–SNARE interaction. Co-IP/immunofluorescence of FASN with STX17/SNAP29/VAMP8, plasmid rescue, Western blot for autophagy markers, TEM Theranostics Medium 38164137
2015 TSH/TSHR signaling suppresses FASN expression in mature adipocytes through PKA activation and ERK1/2 phosphorylation (but not JNK); pharmacological inhibition of PKA or ERK partially abolishes TSH-induced FASN downregulation. TSH treatment of mature adipocytes, PKA/ERK/JNK inhibitors, CREB phosphorylation assays, mRNA and protein quantification Journal of cellular physiology Medium 25655684
2023 ALC-mediated degradation: FASN knockdown in AML cells reduces FASN protein via autophagic degradation; reduced FASN promotes nuclear translocation of transcription factor EB (TFEB) and activation of CLEAR network genes and lysosomal biogenesis to accelerate granulocytic differentiation. RNAi-mediated FASN knockdown, EGCG treatment, TFEB nuclear translocation assays, CLEAR network gene expression, ATRA differentiation model in APL cell lines Cell death and differentiation Medium 33742137
2021 Dihydroartemisinin (DHA) decreases FASN levels, which increases malonylation of mTOR at K1218 and attenuates mTORC1 activity; reduced mTORC1 further inhibits FASN via decreased p70S6K phosphorylation and reduced SREBP-1 binding to the FASN promoter, forming a feedback loop that suppresses retinal vascular dysfunction. DHA treatment in diabetic mice and HRMECs, siRNA against FASN, K1218 mTOR mutagenesis, malonylation assays, SREBP-1 ChIP at FASN promoter (positions -64 and -55) Pharmacological research Medium 34619345
2023 FASN de novo lipogenesis is required for alveolar type II (AEC2) cell surfactant phospholipid composition; conditional deletion of Fasn in AEC2 cells (FasniΔAEC2) causes altered surfactant phospholipidome, increased surface tension, higher lung inflammation, and more severe airspace enlargement upon cigarette smoke exposure. AEC2-specific Fasn conditional KO, BALF lipidomics, surfactant tension assay, lung histology, neutrophil/protein BALF quantification JCI insight Medium 37606038
2018 PKM2 physically interacts with SREBP-1c; PKM2 downregulation reduces SREBP-1c expression via inactivation of the AKT/mTOR signaling pathway, which in turn suppresses FASN transcription and fatty acid synthesis in bladder cancer cells. Co-IP of PKM2–SREBP-1c, PKM2 knockdown, AKT/mTOR pathway inhibitors, FASN/SREBP-1c Western blots, anti-proliferation assays Journal of cellular physiology Medium 30221356
2023 FABP5 interacts with FASN and promotes its degradation via the ubiquitin-proteasome pathway in pancreatic neuroendocrine neoplasms; reduced FASN from FABP5-mediated degradation suppresses Wnt/β-catenin pathway activation and lipid droplet deposition. Co-IP of FABP5–FASN, ubiquitination assays, FABP5 KD/OE, orlistat FASN inhibitor rescue, in vitro and in vivo assays Cancer science Medium 37302809
2024 DPP3 stabilizes FASN protein (through an unspecified mechanism) to promote fatty acid synthesis and tumor cell proliferation and migration in breast cancer. DPP3 KO in breast cancer cell lines, GSEA of lipid metabolism pathways, Western blot for FASN, metabolomics of free fatty acids Acta biochimica et biophysica Sinica Low 38655619
2024 Aryl hydrocarbon receptor (AhR) activation by indole-3-acetic acid (3-IAA, from gut Parabacteroides distasonis) downregulates FASN transcription in bladder cancer cells; reduced FASN decreases the MUFA/PUFA ratio, increasing ferroptosis sensitivity. AhR activation assays, FASN promoter reporter/ChIP-type analysis inferred, FASN knockdown, lipid profiling (MUFA/PUFA), ferroptosis assays in vitro and in vivo Advanced science Medium 40557796
2025 Computational studies confirm TVB-3166 and TVB-3664 bind the FASN ketoacyl reductase (KR) domain as uncompetitive inhibitors towards NADPH; FASN inhibition causes NADPH accumulation that parallels sensitivity of PDAC cells to apoptosis. Computational docking/kinetics of FASNi binding to KR domain, NADPH accumulation assays, BH3 profiling, in vivo PDX xenograft combination experiments Neoplasia Medium 39999714

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2017 Fatty acid synthase (FASN) as a therapeutic target in breast cancer. Expert opinion on therapeutic targets 215 28922023
2019 Toll-like receptor mediated inflammation requires FASN-dependent MYD88 palmitoylation. Nature chemical biology 163 31427815
2006 Pharmacological inhibitors of Fatty Acid Synthase (FASN)--catalyzed endogenous fatty acid biogenesis: a new family of anti-cancer agents? Current pharmaceutical biotechnology 154 17168665
2022 Therapeutic efficacy of FASN inhibition in preclinical models of HCC. Hepatology (Baltimore, Md.) 98 35076948
2022 FASN promotes lymph node metastasis in cervical cancer via cholesterol reprogramming and lymphangiogenesis. Cell death & disease 97 35597782
2024 FASN Inhibition Decreases MHC-I Degradation and Synergizes with PD-L1 Checkpoint Blockade in Hepatocellular Carcinoma. Cancer research 87 38486485
2020 FASN-Dependent Lipid Metabolism Links Neurogenic Stem/Progenitor Cell Activity to Learning and Memory Deficits. Cell stem cell 87 32386572
2014 Up-regulated FASN expression promotes transcoelomic metastasis of ovarian cancer cell through epithelial-mesenchymal transition. International journal of molecular sciences 83 24979135
2021 Fatty acid synthase (FASN) regulates the mitochondrial priming of cancer cells. Cell death & disease 82 34675185
2023 FBXW7β loss-of-function enhances FASN-mediated lipogenesis and promotes colorectal cancer growth. Signal transduction and targeted therapy 79 37202390
2012 microRNA-195 suppresses osteosarcoma cell invasion and migration in vitro by targeting FASN. Oncology letters 74 23162665
2024 The implications of FASN in immune cell biology and related diseases. Cell death & disease 71 38272906
2021 Research progress on FASN and MGLL in the regulation of abnormal lipid metabolism and the relationship between tumor invasion and metastasis. Frontiers of medicine 71 33973101
2012 Genome-wide linkage and association analyses implicate FASN in predisposition to Uterine Leiomyomata. American journal of human genetics 71 23040493
2008 Proto-oncogene FBI-1 (Pokemon) and SREBP-1 synergistically activate transcription of fatty-acid synthase gene (FASN). The Journal of biological chemistry 68 18682402
2018 Down-regulation of PKM2 decreases FASN expression in bladder cancer cells through AKT/mTOR/SREBP-1c axis. Journal of cellular physiology 67 30221356
2019 Fatty Acid Inhibition Sensitizes Androgen-Dependent and -Independent Prostate Cancer to Radiotherapy via FASN/NF-κB Pathway. Scientific reports 66 31527721
2024 The m6A modification mediated-lncRNA POU6F2-AS1 reprograms fatty acid metabolism and facilitates the growth of colorectal cancer via upregulation of FASN. Molecular cancer 64 38491348
2023 CircRNA MBOAT2 promotes intrahepatic cholangiocarcinoma progression and lipid metabolism reprogramming by stabilizing PTBP1 to facilitate FASN mRNA cytoplasmic export. Cell death & disease 59 36635270
2023 FABP5 suppresses colorectal cancer progression via mTOR-mediated autophagy by decreasing FASN expression. International journal of biological sciences 56 37416772
2014 Inhibition of FASN reduces the synthesis of medium-chain fatty acids in goat mammary gland. Animal : an international journal of animal bioscience 56 24909980
2024 ZDHHC20 mediated S-palmitoylation of fatty acid synthase (FASN) promotes hepatocarcinogenesis. Molecular cancer 52 39696259
2021 Reducing FASN expression sensitizes acute myeloid leukemia cells to differentiation therapy. Cell death and differentiation 51 33742137
2024 FASN-mediated fatty acid biosynthesis remodels immune environment in Clonorchis sinensis infection-related intrahepatic cholangiocarcinoma. Journal of hepatology 50 38508240
2016 A FASN-TGF-β1-FASN regulatory loop contributes to high EMT/metastatic potential of cisplatin-resistant non-small cell lung cancer. Oncotarget 49 27765901
2023 CircRREB1 mediates lipid metabolism related senescent phenotypes in chondrocytes through FASN post-translational modifications. Nature communications 48 37640697
2021 SREBP1/FASN/cholesterol axis facilitates radioresistance in colorectal cancer. FEBS open bio 48 33665967
2019 Anoikis resistant mediated by FASN promoted growth and metastasis of osteosarcoma. Cell death & disease 47 30931932
2017 Association between FASN gene polymorphisms ultrasound carcass traits and intramuscular fat in Qinchuan cattle. Gene 43 29273553
2020 Echinacoside ameliorates alcohol-induced oxidative stress and hepatic steatosis by affecting SREBP1c/FASN pathway via PPARα. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association 42 33378712
2021 FASN inhibition as a potential treatment for endocrine-resistant breast cancer. Breast cancer research and treatment 41 33893909
2024 GSTM3 enhances radiosensitivity of nasopharyngeal carcinoma by promoting radiation-induced ferroptosis through USP14/FASN axis and GPX4. British journal of cancer 40 38228715
2022 FASN-dependent de novo lipogenesis is required for brain development. Proceedings of the National Academy of Sciences of the United States of America 40 34996870
2010 Inverse relation between FASN expression in human adipose tissue and the insulin resistance level. Nutrition & metabolism 40 20148112
2020 MicroRNA-103 represses hepatic de novo lipogenesis and alleviates NAFLD via targeting FASN and SCD1. Biochemical and biophysical research communications 38 32035613
2023 EIF4A3-induced circZFAND6 promotes breast cancer proliferation and metastasis through the miR-647/FASN axis. Life sciences 37 37127184
2019 Clinical importance of FASN in relation to HIF-1α and SREBP-1c in gastric adenocarcinoma. Life sciences 34 30914315
2024 Targeting ZDHHC21/FASN axis for the treatment of diffuse large B-cell lymphoma. Leukemia 33 38195819
2023 The m6A modification-mediated OGDHL exerts a tumor suppressor role in ccRCC by downregulating FASN to inhibit lipid synthesis and ERK signaling. Cell death & disease 31 37626050
2020 FASN Protein Overexpression Indicates Poor Biochemical Recurrence-Free Survival in Prostate Cancer. Disease markers 30 32655718
2018 Inhibition of FASN expression enhances radiosensitivity in human non-small cell lung cancer. Oncology letters 30 29541228
2011 Expression of fatty acid synthase (FASN) in oral nevi and melanoma. Oral diseases 30 21819495
2023 Hepatic FASN deficiency differentially affects nonalcoholic fatty liver disease and diabetes in mouse obesity models. JCI insight 29 37681411
2021 Long noncoding RNA SNHG25 promotes the malignancy of endometrial cancer by sponging microRNA-497-5p and increasing FASN expression. Journal of ovarian research 29 34789312
2023 FABP5 regulates lipid metabolism to facilitate pancreatic neuroendocrine neoplasms progression via FASN mediated Wnt/β-catenin pathway. Cancer science 28 37302809
2023 Si-Ni-San inhibits hepatic Fasn expression and lipid accumulation in MAFLD mice through AMPK/p300/SREBP-1c axis. Phytomedicine : international journal of phytotherapy and phytopharmacology 28 37984123
2022 Targeting the SREBP-1/Hsa-Mir-497/SCAP/FASN Oncometabolic Axis Inhibits the Cancer Stem-like and Chemoresistant Phenotype of Non-Small Cell Lung Carcinoma Cells. International journal of molecular sciences 27 35806291
2023 Alveolar type II epithelial cell FASN maintains lipid homeostasis in experimental COPD. JCI insight 26 37606038
2013 FASN and CD36 predict survival in rituximab-treated diffuse large B-cell lymphoma. Journal of hematopathology 26 25937841
2012 Reduced expression of FASN through SREBP-1 down-regulation is responsible for hypoxic cell death in HepG2 cells. Journal of cellular biochemistry 24 22786746
2024 CircHIPK3 regulates fatty acid metabolism through miR-637/FASN axis to promote esophageal squamous cell carcinoma. Cell death discovery 23 38431720
2024 Darolutamide-mediated phospholipid remodeling induces ferroptosis through the SREBP1-FASN axis in prostate cancer. International journal of biological sciences 23 39309439
2024 Fatty acid synthase (FASN) is a tumor-cell-intrinsic metabolic checkpoint restricting T-cell immunity. Cell death discovery 23 39349429
2016 FASN, ErbB2-mediated glycolysis is required for breast cancer cell migration. Oncology reports 23 26936618
2023 Enhanced De Novo Lipid Synthesis Mediated by FASN Induces Chemoresistance in Colorectal Cancer. Cancers 22 36765520
2022 The Deubiquitinase USP13 Maintains Cancer Cell Stemness by Promoting FASN Stability in Small Cell Lung Cancer. Frontiers in oncology 21 35898882
2015 TSH/TSHR Signaling Suppresses Fatty Acid Synthase (FASN) Expression in Adipocytes. Journal of cellular physiology 21 25655684
2024 MK8722 initiates early-stage autophagy while inhibiting late-stage autophagy via FASN-dependent reprogramming of lipid metabolism. Theranostics 20 38164137
2023 Role of EGFR and FASN in breast cancer progression. Journal of cell communication and signaling 20 37490191
2021 Deregulated FASN Expression in BRAF Inhibitor-Resistant Melanoma Cells Unveils New Targets for Drug Combinations. Cancers 20 34068792
2019 Mitochondrial targeting nano-curcumin for attenuation on PKM2 and FASN. Colloids and surfaces. B, Biointerfaces 20 31377611
2025 Gut Parabacteroides distasonis-derived Indole-3-Acetic Acid Promotes Phospholipid Remodeling and Enhances Ferroptosis Sensitivity via the AhR-FASN Axis in Bladder Cancer. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 19 40557796
2024 Fatty acid synthase (FASN) signalome: A molecular guide for precision oncology. Molecular oncology 19 38158755
2023 TAF15 exacerbates nonalcoholic steatohepatitis progression by regulating lipid metabolism and inflammation via FASN and p65 NF-κB. Liver international : official journal of the International Association for the Study of the Liver 19 37183512
2023 TRIM21 ameliorates hepatic glucose and lipid metabolic disorders in type 2 diabetes mellitus by ubiquitination of PEPCK1 and FASN. Cellular and molecular life sciences : CMLS 19 37249651
2020 Gene and immunohistochemical expression of HIF-1α, GLUT-1, FASN, and adipophilin in carcinoma ex pleomorphic adenoma development. Oral diseases 19 32180291
2024 PITPNC1 Suppress CD8+ T cell immune function and promote radioresistance in rectal cancer by modulating FASN/CD155. Journal of translational medicine 18 38291470
2019 Variation in the Fatty Acid Synthase Gene (FASN) and Its Association with Milk Traits in Gannan Yaks. Animals : an open access journal from MDPI 18 31461906
2012 The "HER2-PI3K/Akt-FASN Axis" regulated malignant phenotype of colorectal cancer cells. Lipids 18 22218925
2023 FASN multi-omic characterization reveals metabolic heterogeneity in pancreatic and prostate adenocarcinoma. Journal of translational medicine 17 36650542
2023 Exosomes derived from impaired liver aggravate alveolar bone loss via shuttle of Fasn in type 2 diabetes mellitus. Bioactive materials 17 38024229
2021 Dihydroartemisinin ameliorates retinal vascular dysfunction in diabetes mellitus via the FASN/Kmal-mTOR/SREBP1 feedback loop. Pharmacological research 17 34619345
2017 MAPK/P53-mediated FASN expression in bone tumors. Oncology letters 17 28588696
2025 Lipogenic enzyme FASN promotes mutant p53 accumulation and gain-of-function through palmitoylation. Nature communications 16 39971971
2025 FTO-induced APOE promotes the malignant progression of pancreatic neuroendocrine neoplasms through FASN-mediated lipid metabolism. International journal of biological sciences 16 39990672
2024 Metabolic reprogramming based on RNA sequencing of gemcitabine-resistant cells reveals the FASN gene as a therapeutic for bladder cancer. Journal of translational medicine 16 38218866
2023 Resensitizing Paclitaxel-Resistant Ovarian Cancer via Targeting Lipid Metabolism Key Enzymes CPT1A, SCD and FASN. International journal of molecular sciences 16 38003694
2021 Ovine ELOVL5 and FASN genes polymorphisms and their correlations with sheep tail fat deposition. Gene 16 34500050
2020 FASN-Mediated Lipid Metabolism Regulates Goose Granulosa Cells Apoptosis and Steroidogenesis. Frontiers in physiology 16 32676035
2015 HCBP6 Modulates Triglyceride Homeostasis in Hepatocytes Via the SREBP1c/FASN Pathway. Journal of cellular biochemistry 16 25855506
2025 FASN promotes lipid metabolism and progression in colorectal cancer via the SP1/PLA2G4B axis. Cell death discovery 15 40148316
2024 FASN contributes to ADM resistance of diffuse large B-cell lymphoma by inhibiting ferroptosis via nf-κB/STAT3/GPX4 axis. Cancer biology & therapy 15 39345091
2023 FASN deficiency induces a cytosol-to-mitochondria citrate flux to mitigate detachment-induced oxidative stress. Cell reports 15 37578864
2021 FASN inhibition sensitizes metastatic OSCC cells to cisplatin and paclitaxel by downregulating cyclin B1. Oral diseases 15 34510641
2020 Elevated miR-10a-5p facilitates cell cycle and restrains adipogenic differentiation via targeting Map2k6 and Fasn, respectively. Acta biochimica et biophysica Sinica 15 33128541
2025 Targeting cancer metabolism: Therapeutic potential of the fatty acid synthase (FASN) inhibitors. Critical reviews in oncology/hematology 14 40846043
2015 Global gene deregulations in FASN silenced retinoblastoma cancer cells: molecular and clinico-pathological correlations. Journal of cellular biochemistry 14 25958981
2025 Targeting FASN enhances cisplatin sensitivity via SLC7A11-mediated ferroptosis in cervical cancer. Translational oncology 13 40239242
2024 FASN regulates STING palmitoylation via malonyl-CoA in macrophages to alleviate sepsis-induced liver injury. Biochimica et biophysica acta. Molecular basis of disease 13 38878833
2025 Fatty acid synthase (FASN) inhibition cooperates with BH3 mimetic drugs to overcome resistance to mitochondrial apoptosis in pancreatic cancer. Neoplasia (New York, N.Y.) 12 39999714
2022 Alpinumisoflavone Exhibits the Therapeutic Effect on Prostate Cancer Cells by Repressing AR and Co-Targeting FASN- and HMGCR-Mediated Lipid and Cholesterol Biosynthesis. Life (Basel, Switzerland) 12 36362924
2020 ACAA2 and FASN polymorphisms affect the fatty acid profile of Chios sheep milk. The Journal of dairy research 12 32008581
2020 Pulsatilla saponin E suppresses viability, migration, invasion and promotes apoptosis of NSCLC cells through negatively regulating Akt/FASN pathway via inhibition of flotillin-2 in lipid raft. Journal of receptor and signal transduction research 12 33243063
2024 FASN Gene Methylation is Associated with Fatty Acid Synthase Expression and Clinical-genomic Features of Prostate Cancer. Cancer research communications 11 38112617
2024 DPP3 promotes breast cancer tumorigenesis by stabilizing FASN and promoting lipid synthesis. Acta biochimica et biophysica Sinica 11 38655619
2024 VCP enhances autophagy-related osteosarcoma progression by recruiting USP2 to inhibit ubiquitination and degradation of FASN. Cell death & disease 11 39489738
2024 Ferulic Acid Alleviates Lipid and Bile Acid Metabolism Disorders by Targeting FASN and CYP7A1 in Iron Overload-Treated Mice. Antioxidants (Basel, Switzerland) 11 39594419
2023 FASN promotes gallbladder cancer progression and reduces cancer cell sensitivity to gemcitabine through PI3K/AKT signaling. Drug discoveries & therapeutics 11 37743521
2022 Hypomethylated gene RAC3 induces cell proliferation and invasion by increasing FASN expression in endometrial cancer. The international journal of biochemistry & cell biology 11 35917927
2022 Integrated Transcriptome and Metabolome Analysis Reveals the Regulatory Mechanisms of FASN in Geese Granulosa Cells. International journal of molecular sciences 11 36499045

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