Affinage

LPCAT1

Lysophosphatidylcholine acyltransferase 1 · UniProt Q8NF37

Length
534 aa
Mass
59.2 kDa
Annotated
2026-06-10
64 papers in source corpus 31 papers cited in narrative 33 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

LPCAT1 is an endoplasmic reticulum-resident, Ca2+-independent acyltransferase that drives the reacylation arm of the Lands cycle, converting lysophosphatidylcholine to phosphatidylcholine with a strong preference for saturated palmitoyl-CoA and additionally producing alkyl-PC from lyso-PAF (PMID:16704971, PMID:18974965, PMID:19773578). Its catalytic output is governed by an N-terminal acyltransferase activity that is negatively regulated by Ca2+ binding to a C-terminal EF-hand (residues Asp392/Glu403) and by the cellular redox state of an active-site cysteine (PMID:22676268). In lung alveolar type II cells LPCAT1 is required for synthesis of surfactant saturated PC, and its loss causes neonatal respiratory failure with atelectasis and surfactant dysfunction (PMID:20407208); the enzyme partners with the phospholipid transfer protein StarD10 (via LPCAT1 residues 79–271 and the START domain) to traffic saturated PC from the ER to lamellar bodies, and AT2-specific deletion impairs progenitor renewal and predisposes to lung fibrosis (PMID:26048993). Beyond bulk lipid synthesis, LPCAT1 translocates to the nucleus in response to Ca2+, where it binds histone H4 and catalyzes O-palmitoylation at Ser47 to control global mRNA synthesis (PMID:21685381). LPCAT1 abundance is set post-translationally by ubiquitin-dependent degradation: GSK-3β phosphorylates a Ser178 phosphodegron to license SCF-β-TrCP-mediated polyubiquitination at Lys221 (PMID:21068446). Through these activities LPCAT1 acts broadly in disease, and genetically its loss directly causes rd11 photoreceptor degeneration, rescued by AAV-mediated cDNA delivery (PMID:24557352). In cancer, LPCAT1 increases membrane phospholipid saturation to deplete polyunsaturated fatty acids and confer ferroptosis resistance (PMID:38671262), and across multiple tumor types it activates PI3K/AKT and downstream growth and metabolic programs (PMID:30791942, PMID:34518524, PMID:38671262).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2006 High

    Established the core biochemical identity of LPCAT1 — what reaction it catalyzes and with what substrate selectivity — defining it as the Lands-cycle reacylation enzyme.

    Evidence cDNA cloning and heterologous expression in CHO cells with in vitro acyltransferase assay and tissue profiling

    PMID:16704971

    Open questions at the time
    • No structural model of the catalytic site
    • Did not address regulation or in vivo requirement
  2. 2008 Medium

    Localized LPCAT1 activity to the ER (and mitochondria) and confirmed it drives palmitate incorporation into PC in cells, anchoring the enzyme to a membrane compartment.

    Evidence Overexpression in COS7 with subcellular fractionation and radiolabeled palmitate incorporation

    PMID:18974965

    Open questions at the time
    • Mitochondrial localization not independently confirmed
    • Overexpression artifact possible
  3. 2009 Medium

    Extended LPCAT1 substrate scope to lyso-PAF, showing it both generates anti-inflammatory PC and inactivates the pro-inflammatory lipid mediator PAF.

    Evidence Acyltransferase assays with lyso-PAF/LPC and diabetic mouse retina/brain models

    PMID:19773578

    Open questions at the time
    • Causal role of LPCAT1 loss in diabetic neuropathy not tested by genetic LOF
  4. 2010 High

    Demonstrated the physiological requirement for LPCAT1 in surfactant PC homeostasis and identified its post-translational control by ubiquitin-dependent degradation.

    Evidence Hypomorphic gene-trap mice with surfactant assays; co-IP, phosphodegron/ubiquitin-site mutagenesis (S178, K221) and rescue by GSK-3β/β-TrCP knockdown

    PMID:20407208 PMID:21068446

    Open questions at the time
    • Other E3 ligases not yet defined
    • Trigger linking inflammation to GSK-3β activation incompletely mapped
  5. 2011 High

    Revealed an unexpected nuclear, chromatin-modifying function: Ca2+-triggered nuclear LPCAT1 palmitoylates histone H4 at Ser47 to regulate global mRNA synthesis.

    Evidence Subcellular fractionation, co-IP with H4, H4-S47A mutagenesis, knockdown and mRNA synthesis assay

    PMID:21685381

    Open questions at the time
    • How a lipid acyltransferase reads/writes a serine residue mechanistically unresolved
    • Genome-wide consequences not mapped
  6. 2012 High

    Defined the regulatory architecture of the enzyme — a C-terminal EF-hand confers Ca2+ inhibition of the N-terminal catalytic domain, and a cysteine confers redox sensitivity.

    Evidence Site-directed mutagenesis (D392A/E403A), Ca2+ titration and sulfhydryl-modifier assays in vitro

    PMID:22676268

    Open questions at the time
    • Physiological Ca2+ concentrations triggering inhibition not established
    • No crystal structure of the regulated enzyme
  7. 2014 High

    Provided causal genetic proof that LPCAT1 loss of function drives photoreceptor degeneration, distinct from its lung role.

    Evidence AAV8-mediated Lpcat1 cDNA rescue in rd11 mice with ERG, OCT, IHC and behavioral readouts

    PMID:24557352

    Open questions at the time
    • Specific retinal lipid species rescued not defined
    • Human retinal disease relevance untested
  8. 2015 High

    Identified the trafficking partner that couples LPCAT1 PC synthesis to surfactant delivery, placing it at the ER-to-lamellar-body step.

    Evidence Reciprocal co-IP/pulldown with domain mapping (LPCAT1 79–271, StarD10 START) and StarD10 knockdown trafficking assay

    PMID:26048993

    Open questions at the time
    • Whether interaction directly hands off lipid vs. co-localizes not resolved
    • Stoichiometry of complex unknown
  9. 2019 Medium

    Initiated the body of evidence that LPCAT1 acts as an oncogenic driver through PI3K/AKT signaling and downstream transcriptional targets.

    Evidence shRNA depletion with in vitro and in vivo brain-metastasis models, RNA-seq and pathway-activator rescue

    PMID:30791942

    Open questions at the time
    • Whether catalytic activity is required for PI3K/AKT effect not separated from scaffolding
    • Direct link from lipid output to MYC unclear
  10. 2021 Medium

    Mapped a dense transcriptional and post-translational regulatory network controlling LPCAT1 levels across tissues, and linked LPCAT1 to multiple cancer signaling pathways.

    Evidence ChIP/reporter (NRF1, SOX2, MNRR1), translational control (ROBO4 polyribosome assay), E3 ligase co-IP/ubiquitination (HECTD2), miR-205 targeting, and STAT/PI3K pathway assays across HCC, OS, macrophage and other models

    PMID:32140075 PMID:32334831 PMID:33618181 PMID:33909026 PMID:34178664 PMID:34518524 PMID:35964314 PMID:37875967 PMID:41358198

    Open questions at the time
    • Many regulators tested in single cell types only
    • HECTD2 and miR-205 links rest on limited mechanistic follow-up
  11. 2022 Medium

    Broadened LPCAT1's disease reach to additional cancers and tissues via shared PI3K/AKT, STAT3, and TGF-β effector programs and drug-resistance phenotypes.

    Evidence Gain/loss-of-function with pathway markers, lipidomics, IL-6 and EGFR rescue, FOXA1 ChIP, and pharmacological inhibition (TSI-01) across LUAD, cervical, breast, endometrial models

    PMID:35399731 PMID:35880567 PMID:36122769 PMID:36909375

    Open questions at the time
    • Tissue-specific effectors (GLUT3, JAK2, Smad) reported in isolation
    • Catalytic vs. non-catalytic contribution often untested
  12. 2024 High

    Unified LPCAT1's lipid biochemistry with a major cancer phenotype by showing it depletes membrane PUFAs to confer ferroptosis resistance, and added a hypoxia-driven transcriptional/metabolic axis.

    Evidence Gain/loss-of-function with membrane lipidomics, ferroptosis induction and combination therapy in vivo; HIF-2α ChIP with RNA-seq, lipidomics and FBXW7-ACLY ubiquitination assays

    PMID:38671262 PMID:39781455

    Open questions at the time
    • Whether the EF-hand/redox regulation modulates ferroptosis output untested
    • FBXW7-ACLY arm characterized in single model
  13. 2025 Medium

    Demonstrated tissue-progenitor and stability-regulation roles — AT2 renewal, oligodendrocyte differentiation, and LRRK2/RBX1 control of LPCAT1 protein stability.

    Evidence Conditional knockouts and organoid assays (lung AT2, oligodendrocyte lineage), ZBTB20/mTOR Western blot, and RBX1 co-IP/degradation assays with PROTAC targeting

    PMID:39878319 PMID:40121376

    Open questions at the time
    • AT2 fibrosis finding is preprint and not peer-reviewed
    • Oligodendrocyte effect reported as PC-independent, leaving the mediating activity unclear
  14. 2026 Medium

    Added further substrate/effector relationships — TRIM33-mediated degradation and an ATF2-LPCAT1-PKM2 acetylation axis — expanding LPCAT1's regulatory inputs and metabolic outputs.

    Evidence Co-IP/ubiquitination (TRIM33), PKM2-K433 mutagenesis and epistasis in cholesterol-loaded macrophages, with pathway and xenograft assays

    PMID:41740546 PMID:42147264

    Open questions at the time
    • Mechanism by which an acyltransferase promotes PKM2 acetylation unresolved
    • Single-lab findings without independent replication

Open questions

Synthesis pass · forward-looking unresolved questions
  • How LPCAT1's distinct activities — ER bulk PC synthesis, nuclear histone palmitoylation, and PUFA-depleting ferroptosis resistance — are coordinated within a cell, and whether its catalytic activity is required for the many reported PI3K/AKT signaling effects, remain unresolved.
  • No structure of full-length human LPCAT1
  • Catalytic vs. scaffolding requirement for oncogenic signaling not systematically dissected
  • Mechanism switching cytosolic vs. nuclear localization beyond Ca2+ unclear

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 4 GO:0042393 histone binding 1 GO:0140096 catalytic activity, acting on a protein 1 GO:0140299 molecular sensor activity 1
Localization
GO:0005783 endoplasmic reticulum 3 GO:0005634 nucleus 2 GO:0005829 cytosol 1
Pathway
R-HSA-1430728 Metabolism 3 R-HSA-392499 Metabolism of proteins 1 R-HSA-5357801 Programmed Cell Death 1 R-HSA-74160 Gene expression (Transcription) 1
Partners
BTRCGSK3BHECTD2HIST1H4 (HISTONE H4)RBX1STARD10STAT1TRIM33
Complex memberships
LPCAT1-StarD10 complex

Evidence

Reading pass · 33 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2006 Mouse LPCAT1 encodes a 60 kDa enzyme with three putative transmembrane domains that catalyzes Ca2+-independent acyltransferase activity (pH optimum 7.4–10), with a clear preference for saturated fatty acyl-CoAs (palmitoyl-CoA) and 1-palmitoyl-LPC as substrate, converting LPC to PC. The enzyme is predominantly expressed in lung alveolar type II cells. cDNA cloning, heterologous expression in CHO cells, in vitro acyltransferase activity assay, tissue expression profiling The Journal of biological chemistry High 16704971
2010 LPCAT1 is required for surfactant phosphatidylcholine (SatPC) homeostasis in vivo. Hypomorphic Lpcat1GT/GT mice showed reduced LPCAT1 mRNA levels that directly correlated with SatPC content, LPCAT1 activity, and survival. Newborn Lpcat1GT/GT mice died from respiratory failure with atelectasis and hyaline membranes, and their surfactant failed to reduce minimum surface tension to wild-type levels. Gene-trap hypomorphic mouse model, biochemical assay of SatPC content and LPCAT1 activity, surfactant function measurement The Journal of clinical investigation High 20407208
2008 Overexpressed LPCAT1 localizes to the endoplasmic reticulum and mitochondria in COS7 cells, increases LPCAT1-specific acyltransferase activity 38-fold, and enhances incorporation of [14C]palmitate into phosphatidylcholine. Overexpression in COS7 cells, subcellular fractionation/localization, radiolabeled palmitate incorporation assay, enzymatic activity measurement Journal of molecular medicine (Berlin, Germany) Medium 18974965
2009 LPCAT1 catalyzes two reactions in the retina: (1) conversion of LPC to PC (anti-inflammatory) and (2) synthesis of alkyl-PC (an inactivated form of PAF) from lyso-PAF and acyl-CoA, thereby inactivating PAF. LPCAT1 mRNA levels and acyltransferase activity toward lyso-PAF and LPC were significantly downregulated in retina and brain of diabetic mice (Ins2Akita and db/db models), while rosiglitazone treatment restored LPCAT1 activity. Acyltransferase activity assay with lyso-PAF and LPC substrates, qPCR, diabetic mouse models (Ins2Akita, db/db), pharmacological treatment American journal of physiology. Endocrinology and metabolism Medium 19773578
2011 LPCAT1 translocates from the cytosol to the nucleus in lung epithelia in response to exogenous Ca2+, where it directly binds histone H4 and catalyzes O-palmitoylation of histone H4 at Ser47. This nuclear LPCAT1-mediated histone H4 palmitoylation regulates global mRNA synthesis, as LPCAT1 knockdown or expression of a H4-S47A mutant decreased cellular mRNA synthesis. Subcellular fractionation, co-immunoprecipitation, site-directed mutagenesis (H4-S47A), LPCAT1 knockdown, nuclear translocation imaging, mRNA synthesis assay The Journal of biological chemistry High 21685381
2010 LPS triggers proteasomal degradation of LPCAT1 via the SCF-β-TrCP E3 ubiquitin ligase. GSK-3β phosphorylates LPCAT1 at Ser178 within a phosphodegron, enabling β-TrCP docking and subsequent polyubiquitination at Lys221. Substitution of K221R abolished polyubiquitination. siRNA to β-TrCP or GSK-3β rescued LPCAT1 levels and lung surfactant mechanics impaired by LPS. Co-immunoprecipitation, site-directed mutagenesis (S178, K221), ubiquitination assay, siRNA knockdown, surfactant function assay, LPS treatment The Journal of biological chemistry High 21068446
2012 LPCAT1 acyltransferase activity is negatively regulated by Ca2+ binding through an EF-hand motif (EFh-1) in its C-terminal domain; residues Asp392 and Glu403 define the Ca2+-binding loop. Substitution of D392A/E403A rendered the enzyme insensitive to Ca2+ inhibition, establishing that Ca2+ binding to the C-terminal domain negatively regulates the N-terminal acyltransferase activity. Additionally, an active cysteine mutant was identified that is resistant to sulfhydryl-alkylating and sulfhydryl-oxidizing agents, placing PC synthesis under control of both Ca2+ and the cellular redox status. Site-directed mutagenesis, in vitro acyltransferase activity assay, Ca2+ titration, sulfhydryl modifier treatment BMC biochemistry High 22676268
2014 Lpcat1 mutation (spontaneous insertion in rd11 mice) causes photoreceptor degeneration. AAV8(Y733F)-mediated subretinal delivery of Lpcat1 cDNA preserved the outer nuclear layer, restored rod and cone opsin expression, rescued ERG responses, and recovered visually-guided behavior, establishing that LPCAT1 loss of function is the direct cause of rd11 retinal degeneration. AAV gene replacement therapy, ERG, SD-OCT, immunohistochemistry, visually-guided behavior assay Investigative ophthalmology & visual science High 24557352
2015 LPCAT1 directly and specifically interacts with the phospholipid transfer protein StarD10 in alveolar type II cells; amino acids 79–271 of LPCAT1 and the START domain of StarD10 are sufficient for this interaction. StarD10 knockdown significantly reduced phospholipid transport to lamellar bodies, placing LPCAT1-StarD10 interaction at the step of SatPC trafficking from ER to lamellar bodies. Co-immunoprecipitation, pulldown with truncation/deletion mutants, StarD10 siRNA knockdown, phospholipid trafficking assay to lamellar bodies The Journal of biological chemistry High 26048993
2019 LPCAT1 promotes lung adenocarcinoma brain metastasis at least partially through the PI3K/AKT signaling pathway by targeting MYC transcription. shRNA-mediated LPCAT1 depletion abrogated cell proliferation, migration, and invasion in vitro and arrested tumor growth and brain metastases in vivo. shRNA knockdown, in vitro proliferation/migration/invasion assays, in vivo xenograft and brain metastasis model, RNA sequencing, PI3K/AKT pathway activator rescue Journal of experimental & clinical cancer research : CR Medium 30791942
2020 LPCAT1 drives CRPC progression via two mechanisms: (1) nuclear re-localization and histone H4 palmitoylation in an androgen-dependent fashion, increasing mRNA synthesis rates; (2) production of PAF, which enhances cancer cell invasion through the PAF receptor (reversed by PAF-AH and PAF receptor antagonist ABT-491). Exogenous PAF rescued invasion in LPCAT1 knockdown cells. Cell transfection, siRNA knockdown, pulse-chase RNA labeling, migration/invasion assays, exogenous PAF rescue, PAF-AH and ABT-491 inhibition, xenograft model PloS one Medium 33137125
2021 LPCAT1 directly interacts with and suppresses STAT1 protein expression in hepatocellular carcinoma cells. High LPCAT1 leads to decreased STAT1, upregulation of CyclinD1, CyclinE, CDK4, MMP-9, and decreased p27kip1, promoting cell cycle progression and metastasis. Conversely, LPCAT1 knockdown caused opposite changes and arrested HCC cells at G0/G1. Co-immunoprecipitation, knockdown/overexpression, Western blot, cell cycle analysis, in vitro and in vivo tumor assays Frontiers in oncology Medium 34178664
2021 LPCAT1 reprograms cholesterol metabolism in esophageal squamous cell carcinoma by activating PI3K to promote SP1/SREBPF2 nuclear entry (upregulating cholesterol synthesis enzyme SQLE) and by activating EGFR to downregulate INSIG-1, facilitating SREBP-1 nuclear entry and cholesterol synthesis. LPCAT1 knockdown/overexpression, Western blot for PI3K, EGFR, SREBP-1, INSIG-1, SQLE, SP1/SREBPF2 nuclear fractionation, xenograft model Cell death & disease Medium 34518524
2021 LPCAT1 is identified as a transcriptional target of nuclear respiratory factor 1 (NRF1) in hepatocellular carcinoma. NRF1 transactivates LPCAT1, which in turn activates ERK1/2-CREB signaling, and activated CREB then further upregulates NRF1, forming a positive feedback loop that promotes HCC cell cycle progression and EMT. ChIP/luciferase reporter assay for NRF1-LPCAT1 transcriptional activation, Western blot for ERK1/2-CREB, knockdown/overexpression, in vitro and in vivo assays Biology direct Medium 37875967
2022 LPCAT1 forms a positive feedback loop with EGFR in lung adenocarcinoma: LPCAT1 upregulation activates EGFR/PI3K/AKT signaling, and EGFR activation in turn further increases LPCAT1 expression, conferring gefitinib resistance. LPCAT1 knockdown/overexpression, gefitinib resistance assay, Western blot for EGFR/PI3K/AKT, in vivo and in vitro functional assays Journal of Cancer Medium 35399731
2022 LPCAT1 regulates cervical cancer progression through the JAK2/STAT3 signaling pathway. LPCAT1 knockdown decreased IL-6, p-JAK2, and p-STAT3 levels, and exogenous IL-6 addition abolished the anti-proliferative and pro-apoptotic effects of LPCAT1 knockdown, establishing IL-6/JAK2/STAT3 as downstream of LPCAT1. siRNA knockdown, RNA-seq, Western blot for p-JAK2/p-STAT3/IL-6, exogenous IL-6 rescue, xenograft and lung metastasis model Experimental cell research Medium 36122769
2022 FOXA1 transcriptionally regulates LPCAT1 in breast cancer, as demonstrated by luciferase reporter and chromatin immunoprecipitation assays. FOXA1 overexpression attenuated the effects of LPCAT1 knockdown on cell proliferation, colony formation, migration, invasion, and paclitaxel resistance. Luciferase reporter assay, chromatin immunoprecipitation (ChIP), LPCAT1 knockdown, FOXA1 overexpression rescue Oncology letters Medium 36909375
2022 LPCAT1 overexpression changes phospholipid composition (PE, PC, TG) in endometrial cancer cells and promotes stemness and metastasis through activation of the TGF-β/Smad2/3 signaling pathway, upregulating stem cell transcription factors and EMT-related proteins. The LPCAT1 inhibitor TSI-01 restrained EC cell proliferation and promoted apoptosis. LPCAT1 knockdown/overexpression, lipidomics, RNA sequencing, Western blot for Smad2/3, TSI-01 pharmacological inhibition Acta biochimica et biophysica Sinica Medium 35880567
2021 HECTD2, a HECT-domain E3 ubiquitin ligase, co-immunoprecipitates with ubiquitinated LPCAT1 and drives LPCAT1 polyubiquitination and degradation. LPCAT1 overexpression rescued CRC cell proliferation impaired by HECTD2 overexpression, placing HECTD2 as an upstream negative regulator of LPCAT1. Co-immunoprecipitation, ubiquitination assay, HECTD2 and LPCAT1 overexpression, cell proliferation rescue assay Molekuliarnaia biologiia Low 35964314
2021 miR-205 directly targets LPCAT1 in multiple cancer cell lines (LIHC, HNSCC, LUSC), and LPCAT1 is required for sustained cancer cell proliferation downstream of miR-205 suppression. miR-205 stable overexpression, luciferase/target validation (implied), cell proliferation assay Biochemical and biophysical research communications Low 32334831
2021 ROBO4 deletion reduces LPCAT1 (and LPCAT2) protein levels in macrophages without affecting mRNA levels, by decreasing ribosome abundance and ATP levels, which impairs LPCAT1/LPCAT2 mRNA translation efficiency (shown by polyribosome assay). This reduces PAF synthesis and PAF-mediated skin inflammation. ROBO4 knockout mouse model, polyribosome assay, Western blot, HPLC for ATP, RNA expression profiling International journal of biological sciences Medium 32140075
2021 MNRR1 (mitochondrial nuclear retrograde regulator 1), a bi-organellar transcription regulator, transcriptionally activates LPCAT1. Dexamethasone (antenatal corticosteroids) upregulates LPCAT1 at least in part through an MNRR1-dependent pathway; in MNRR1 knockout cells, the response of LPCAT1 to dexamethasone is significantly blunted. MNRR1 knockout cells, dexamethasone treatment, Western blot for LPCAT1, hypoxia treatment (4% O2), placental cell line (HTR-8/SVneo) Placenta Medium 33618181
2024 LPCAT1 increases membrane phospholipid saturation via the Lands cycle, reducing membrane polyunsaturated fatty acid (PUFA) levels, thereby protecting cells from phospholipid peroxidation-induced membrane damage and enabling ferroptosis resistance. LPCAT1 inhibition combined with a ferroptosis inducer synergistically triggers ferroptosis and suppresses tumor growth in vivo. LPCAT1 gain/loss-of-function, lipidomics for membrane PUFA content, ferroptosis induction assays, in vivo tumor growth assay, combination treatment Nature cell biology High 38671262
2024 HIF-2α directly binds to the LPCAT1 promoter and transcriptionally activates LPCAT1 in ccRCC. LPCAT1 knockdown activates NF-κB signaling, which upregulates FBXW7 (an E3 ubiquitin ligase); FBXW7 then promotes ubiquitination and degradation of ACLY, lowering fatty acid production and reducing lipid content. RNA-seq and lipidomics confirmed that LPCAT1 knockdown significantly reduced triglyceride production. ChIP/promoter binding assay for HIF-2α-LPCAT1, RNA-seq, lipidomics, NF-κB pathway Western blot, FBXW7-ACLY co-immunoprecipitation and ubiquitination assay International journal of biological sciences Medium 39781455
2025 LRRK2 inhibits RBX1-mediated proteasomal degradation of LPCAT1, thereby stabilizing LPCAT1 protein in ccRCC. LRRK2/LPCAT1 upregulation promotes IL-1β expression through AKT and by activating the inflammasome, reducing sensitivity to TKI and PD-1 blockade. Protein degradation assay, co-immunoprecipitation with RBX1, Western blot for LPCAT1 stability, AKT/inflammasome pathway analysis, PROTAC targeting Oncogene Medium 40121376
2021 ppGalNAc-T18 (GALNT18) retains in the ER through its luminal stem region and catalytic domain interacting with ER resident proteins including LPCAT1, as shown by co-immunoprecipitation. This identifies LPCAT1 as an ER-resident protein involved in ER retention interactions. Co-immunoprecipitation with truncation mutants of ppGalNAc-T18, flow cytometry for O-glycosylation Glycobiology Low 33909026
2025 LPCAT1 promotes OPC differentiation into oligodendrocytes by activating mTOR phosphorylation (not through increased PC production per se). LPCAT1 upregulates the transcription factor ZBTB20, which regulates mTOR phosphorylation. In vivo, conditional knockout of LPCAT1 in oligodendrocyte lineage cells caused complex myelin tomacula but no obvious myelin thickness abnormalities. LPCAT1 overexpression and siRNA knockdown in OPC cultures, RNA sequencing, Western blot for p-mTOR, in vivo conditional knockout, OPC differentiation assay Journal of cellular and molecular medicine Medium 39878319
2024 LPCAT1 promotes keratinocyte hyperproliferation and skin inflammation in psoriasis by activating AKT/NF-κB and STAT3 signaling, which in turn upregulates glucose transporter GLUT3. GLUT3 deficiency impaired proliferation and inflammation of psoriatic keratinocytes, establishing GLUT3 as a critical downstream effector of LPCAT1. LPCAT1 gain/loss-of-function, siRNA for GLUT3, NF-κB and STAT3 pathway inhibition, imiquimod mouse model, cytokine ELISA, GLUT3 rescue assay The Journal of investigative dermatology Medium 38246582
2021 SOX2 transcriptionally activates LPCAT1 in osteosarcoma (validated by dual-luciferase reporter and ChIP assays). LPCAT1 overexpression promoted cholesterol metabolism reprogramming (free cholesterol/total cholesterol levels, SREBP1/INSIG1), proliferation, migration and invasion; LPCAT1 knockdown attenuated SOX2-driven oncogenicity in vitro and in vivo. Dual-luciferase reporter, ChIP, LPCAT1 and SOX2 overexpression/knockdown, cholesterol measurement, xenograft and lung metastasis model Frontiers in molecular biosciences Medium 41358198
2026 TRIM33 directly interacts with LPCAT1 and promotes its ubiquitination and proteasomal degradation. TRIM33 overexpression inhibited LPCAT1-driven PI3K/AKT activation and glycolysis, reversing cisplatin resistance in NSCLC cells in vitro and in vivo. Co-immunoprecipitation, ubiquitination assay, TRIM33 and LPCAT1 overexpression/knockdown, PI3K/AKT Western blot, glycolysis assay, xenograft model World journal of oncology Medium 42147264
2026 ATF2, activated by the p38 MAPK pathway in response to cholesterol loading, transcriptionally upregulates LPCAT1. LPCAT1 in turn promotes acetylation of PKM2 at K433, exacerbating cholesterol-induced metabolic disorders and inflammation in macrophages. K433 mutations ameliorated these effects, establishing the p38-ATF2-LPCAT1-PKM2 axis. p38 MAPK inhibition, ATF2 knockdown, LPCAT1 knockdown, PKM2-K433 mutagenesis, metabolic and inflammatory assays in cholesterol-loaded macrophages Biochemical and biophysical research communications Medium 41740546
2025 AT2 cell-specific Lpcat1 deletion in mice resulted in reduced AT2 cell renewal, spontaneous lung fibrosis, and heightened susceptibility to bleomycin-induced fibrosis in vivo. Pharmacologically, artesunate and PLA2 inhibitor ONO-RS-082 increased LPCAT1 mRNA expression, promoted AT2 renewal, and attenuated bleomycin-induced fibrosis, confirming that LPCAT1 is required for AT2 progenitor renewal through PC metabolism. AT2 cell-specific conditional knockout, 3D organoid AT2 renewal assay, bleomycin fibrosis model, pharmacological LPCAT1 upregulation, LPCAT1 knock-in cell line drug screening bioRxivpreprint Medium
2025 Microbiota-derived lithocholic acid (LCA) directly activates LPCAT1, upregulating its expression. LPCAT1 overexpression leads to intestinal barrier dysfunction and promotes colonic inflammation via activation of MMP1. LPCAT1 inhibition ameliorated intestinal barrier dysfunction, diarrhea symptoms, and colonic inflammation in LCA-treated mice and experimental colitis models. LCA treatment in mice and cell culture, LPCAT1 knockdown/overexpression, MMP1 pathway analysis, in vivo intestinal barrier assays, colitis mouse model bioRxivpreprint Low

Source papers

Stage 0 corpus · 64 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Cloning and characterization of mouse lung-type acyl-CoA:lysophosphatidylcholine acyltransferase 1 (LPCAT1). Expression in alveolar type II cells and possible involvement in surfactant production. The Journal of biological chemistry 203 16704971
2019 LPCAT1 promotes brain metastasis of lung adenocarcinoma by up-regulating PI3K/AKT/MYC pathway. Journal of experimental & clinical cancer research : CR 135 30791942
2010 LPCAT1 regulates surfactant phospholipid synthesis and is required for transitioning to air breathing in mice. The Journal of clinical investigation 129 20407208
2008 Lysophosphatidylcholine acyltransferase 1 (LPCAT1) overexpression in human colorectal cancer. Journal of molecular medicine (Berlin, Germany) 104 18974965
2024 LPCAT1-mediated membrane phospholipid remodelling promotes ferroptosis evasion and tumour growth. Nature cell biology 86 38671262
2021 LPCAT1 reprogramming cholesterol metabolism promotes the progression of esophageal squamous cell carcinoma. Cell death & disease 71 34518524
2011 Acyl-CoA:lysophosphatidylcholine acyltransferase I (Lpcat1) catalyzes histone protein O-palmitoylation to regulate mRNA synthesis. The Journal of biological chemistry 71 21685381
2015 Lysophosphatidylcholine acyltransferase 1 (LPCAT1) upregulation in breast carcinoma contributes to tumor progression and predicts early tumor recurrence. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 67 25683484
2009 A regulatory role of LPCAT1 in the synthesis of inflammatory lipids, PAF and LPC, in the retina of diabetic mice. American journal of physiology. Endocrinology and metabolism 51 19773578
2021 Gut Microbiota Dysbiosis Accelerates Prostate Cancer Progression Through Increased LPCAT1 Expression and Enhanced DNA Repair Pathways. Frontiers in oncology 50 34221998
2018 LPCAT1 controls phosphate homeostasis in a zinc-dependent manner. eLife 50 29453864
2021 LPCAT1 overexpression promotes the progression of hepatocellular carcinoma. Cancer cell international 46 34419067
2010 LPS impairs phospholipid synthesis by triggering beta-transducin repeat-containing protein (beta-TrCP)-mediated polyubiquitination and degradation of the surfactant enzyme acyl-CoA:lysophosphatidylcholine acyltransferase I (LPCAT1). The Journal of biological chemistry 41 21068446
2024 Anti-EGFR ScFv functionalized exosomes delivering LPCAT1 specific siRNAs for inhibition of lung cancer brain metastases. Journal of nanobiotechnology 40 38589859
2012 Phosphatidylcholine formation by LPCAT1 is regulated by Ca(2+) and the redox status of the cell. BMC biochemistry 24 22676268
2020 LPCAT1 enhances castration resistant prostate cancer progression via increased mRNA synthesis and PAF production. PloS one 23 33137125
2014 AAV-mediated lysophosphatidylcholine acyltransferase 1 (Lpcat1) gene replacement therapy rescues retinal degeneration in rd11 mice. Investigative ophthalmology & visual science 22 24557352
2022 Overexpression of LPCAT1 enhances endometrial cancer stemness and metastasis by changing lipid components and activating the TGF/β-Smad2/3 signaling pathway. Acta biochimica et biophysica Sinica 21 35880567
2021 Methylome and transcriptome profiling revealed epigenetic silencing of LPCAT1 and PCYT1A associated with lipidome alterations in polycystic ovary syndrome. Journal of cellular physiology 20 33521992
2021 LPCAT1 Promotes Cutaneous Squamous Cell Carcinoma via EGFR-Mediated Protein Kinase B/p38MAPK Signaling Pathways. The Journal of investigative dermatology 20 34358528
2015 Lysophosphatidylcholine Acyltransferase 1 (LPCAT1) Specifically Interacts with Phospholipid Transfer Protein StarD10 to Facilitate Surfactant Phospholipid Trafficking in Alveolar Type II Cells. The Journal of biological chemistry 20 26048993
2022 LPCAT1 promotes gefitinib resistance via upregulation of the EGFR/PI3K/AKT signaling pathway in lung adenocarcinoma. Journal of Cancer 18 35399731
2022 LPCAT1 functions as an oncogene in cervical cancer through mediating JAK2/STAT3 signaling. Experimental cell research 16 36122769
2021 LpCat1 Promotes Malignant Transformation of Hepatocellular Carcinoma Cells by Directly Suppressing STAT1. Frontiers in oncology 16 34178664
2024 Multiomics analysis reveals the potential of LPCAT1-PC axis as a therapeutic target for human intervertebral disc degeneration. International journal of biological macromolecules 14 38992527
2023 Biomarkers of ulcerative colitis disease activity CXCL1, CYP2R1, LPCAT1, and NEU4 and their relationship to immune infiltrates. Scientific reports 13 37495756
2023 Nuclear respiratory factor 1 drives hepatocellular carcinoma progression by activating LPCAT1-ERK1/2-CREB axis. Biology direct 12 37875967
2021 LPCAT1-TERT fusions are uniquely recurrent in epithelioid trophoblastic tumors and positively regulate cell growth. PloS one 12 34033669
2025 HIF-2α/LPCAT1 orchestrates the reprogramming of lipid metabolism in ccRCC by modulating the FBXW7-mediated ubiquitination of ACLY. International journal of biological sciences 11 39781455
2020 A miR-205-LPCAT1 axis contributes to proliferation and progression in multiple cancers. Biochemical and biophysical research communications 11 32334831
2024 LPCAT1 Facilitates Keratinocyte Hyperproliferation and Skin Inflammation in Psoriasis by Regulating GLUT3. The Journal of investigative dermatology 10 38246582
2023 LPCAT1 is transcriptionally regulated by FOXA1 to promote breast cancer progression and paclitaxel resistance. Oncology letters 9 36909375
2021 Molecular mechanisms regulating lysophosphatidylcholine acyltransferase 1 (LPCAT1) in human pregnancy. Placenta 8 33618181
2022 Circular RNA circZCCHC6 contributes to tumorigenesis by regulating LPCAT1 via miR-433-3p in non-small cell lung cancer. Clinical and experimental medicine 7 35089454
2022 Downregulation of circLPAR3 inhibits tumor progression and glycolysis by liberating miR-144-3p and upregulating LPCAT1 in oral squamous cell carcinoma. Laryngoscope investigative otolaryngology 7 35434335
2020 Genetic Polymorphisms of LPCAT1, CHPT1 and PCYT1B and Risk of Neonatal Respiratory Distress Syndrome among a Chinese Han Population. Pediatrics and neonatology 7 31964590
2024 LPCAT1 promotes melanoma cell proliferation via Akt signaling. Oncology reports 6 38551165
2023 The inhibition of Aurora A kinase regulates phospholipid remodeling by upregulating LPCAT1 in glioblastoma. Neoplasma 6 37226933
2021 Polypeptide N-acetylgalactosaminyltransferase 18 retains in endoplasmic reticulum depending on its luminal regions interacting with ER resident UGGT1, PLOD3 and LPCAT1. Glycobiology 6 33909026
2023 Knockdown of LPCAT1 Repressed Hepatocellular Carcinoma Growth and Invasion by Targeting S100A11. Annals of clinical and laboratory science 5 37094849
2021 Differential lysophosphatidylcholine acyltransferase 1 (LPCAT1) expression confers aggressiveness and independently predicts recurrence in bladder urothelial carcinomas. Journal of histotechnology 5 34378492
2020 ROBO4 deletion ameliorates PAF-mediated skin inflammation via regulating the mRNA translation efficiency of LPCAT1/LPCAT2 and the expression of PAF receptor. International journal of biological sciences 5 32140075
2015 Molecular screening of the LPCAT1 gene in patients with retinitis pigmentosa without defined mutations in known retinitis pigmentosa genes. Molecular medicine reports 4 26260533
2025 LRRK2 reduces the sensitivity to TKI and PD-1 blockade in ccRCC via activating LPCAT1. Oncogene 3 40121376
2025 Inhibition of recurrence and metastasis in triple-negative breast cancer through nanoparticle-mediated silencing of LPCAT1 to remodel ATP energy metabolism. Science China. Life sciences 3 40343577
2023 LPCAT1 enhances the invasion and migration in gastric cancer: Based on computational biology methods and in vitro experiments. Cancer medicine 3 37184260
2025 LPCAT1, the Enzyme Responsible for Converting LPC to PC, Promotes OPC Differentiation In Vitro. Journal of cellular and molecular medicine 2 39878319
2024 Identification of LPCAT1 as a key biomarker for Crohn's disease based on bioinformatics and machine learnings and experimental verification. Gene 2 38703867
2023 LncRNA AC012360.1 facilitates growth and metastasis by regulating the miR-139-5p/LPCAT1 axis in hepatocellular carcinoma. Environmental toxicology 2 37300846
2022 [HECTD2 Represses Cell Proliferation in Colorectal Cancer through Driving Ubiquitination and Degradation of LPCAT1]. Molekuliarnaia biologiia 2 35964314
2025 Association of LPCAT1*rs9728 Variant with Reduced Susceptibility to Neonatal Respiratory Distress Syndrome. Biomedicines 1 41007798
2024 LPCAT1 reduces inflammatory response, apoptosis and barrier damage of nasal mucosal epithelial cells caused by allergic rhinitis through endoplasmic reticulum stress. Tissue & cell 1 39837174
2026 Lysolecithin reprogramming via LPCAT1 modulation restores endothelial function and prevents diabetes-associated dysmetabolism. Cardiovascular diabetology 0 41549297
2026 Oncogenic LPCAT1 Accelerates Intrahepatic Cholangiocarcinoma Development Through PI3K/Akt Signaling-Dependent Cell Cycle Regulation. Journal of gastroenterology and hepatology 0 41711314
2026 ATF2-LPCAT1-mediated PKM2 acetylation links cholesterol stress to macrophage metabolic reprogramming and functional remodeling. Biochemical and biophysical research communications 0 41740546
2026 Reduction in Synaptic Vesicle Protein Abundance but Increased Amounts of Nsg2 and Lpcat1 in Cerebral Cortices Without the Endosomal SNARE Proteins Vti1a and Vti1b. Proteomics 0 41859820
2026 KL-6 assisted subtyping of ARDS: from subtype-specific metabolomics to LPCAT1 as a pathogenic target. Respiratory research 0 41928265
2026 LPCAT1 depletion inhibits colorectal cancer tumorigenesis and is associated with the ECM-receptor-interaction signaling pathway. Scientific reports 0 41986490
2026 TRIM33 Reverses Cisplatin Resistance in Non-Small Cell Lung Cancer by Regulating the PI3K/AKT Pathway via Ubiquitination-Mediated Degradation of LPCAT1. World journal of oncology 0 42147264
2025 Association of LPCAT1-rs8352 genetic variant with susceptibility and severity of pediatric bronchial asthma: a case-control study. BMC pediatrics 0 39871194
2025 SOX2 induces LPCAT1 expression to promote cholesterol metabolic reprogramming-mediated invasion and metastasis in osteosarcoma. Frontiers in molecular biosciences 0 41358198
2023 The validation and clinical significance of LPCAT1 down-regulation in acute myeloid leukemia. Molecular biology reports 0 37079124
2023 LPCAT1 levels in the placenta, the maternal plasma and the fetal plasma do not predict fetal lung responses to glucocorticoids in a sheep model of pregnancy. Placenta 0 37146534
2023 Molecular cloning, tissue expression pattern, responses to different fatty acids and potential functions of lysophosphatidylcholine acyltransferase 1 (LPCAT1) in large yellow croaker (Larimichthys crocea). Gene 0 38042217

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