Affinage

PLAC1

Placenta-specific protein 1 · UniProt Q9HBJ0

Length
212 aa
Mass
23.6 kDa
Annotated
2026-06-10
68 papers in source corpus 29 papers cited in narrative 29 extracted findings
Cross-family judge faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PLAC1 is an X-linked, trophoblast-restricted membrane-associated protein that governs trophoblast differentiation and placental architecture and is co-opted by epithelial cancers to drive proliferation and invasion (PMID:22729990, PMID:27692364, PMID:29704427). The protein carries a signal peptide and a ZP-N module homologous to the polymerization-competent interaction domain of ZP3, whose conserved cysteine disulfide architecture defines a folding unit capable of filament assembly (PMID:10995572, PMID:16600035). In the syncytiotrophoblast PLAC1 localizes to intracellular membranous compartments and the apical microvillous membrane (PMID:17186554), and through the ZP-N cysteines it binds the desmosomal protein Desmoglein-2 (PMID:34118612); its expression rises sharply during cytotrophoblast-to-syncytiotrophoblast differentiation and its knockdown impairs spontaneous syncytialization (PMID:15803460, PMID:27692364). Genetic ablation in mice and rats produces placentomegaly with an expanded junctional/spongiotrophoblast layer, intrauterine growth restriction, and—in mice—lethal hydrocephalus, establishing non-redundant roles in placental and brain development (PMID:22729990, PMID:24014101, PMID:42007670); complementation restores fetal development but supraphysiologic levels themselves cause hyperplasia, showing that dosage is the critical variable (PMID:26586843). Mechanistically, secreted PLAC1 adheres to extracellular matrix and forms a trimeric complex with FGF7 and FGFR2IIIb to activate AKT phosphorylation (PMID:32499871), and intracellularly it physically interacts with the convertase Furin to drive Notch1 cleavage to NICD and suppression of PTEN, promoting tumor invasion and metastasis (PMID:29704427, PMID:33418237). In cancer it sustains proliferation, EMT, and survival through AKT and mTOR/HIF-1α/Snail signaling (PMID:27878289, PMID:39549936), and shapes the tumor immune microenvironment via a CXCL1/chemokine axis required for growth in immunocompetent hosts (PMID:29632317). Its transcription is controlled by SP1 and C/EBPβ-2 with ERα/NCOA3, RXR/LXR nuclear receptors, and the hypoxia-sensitive MED1 coactivator, and is suppressed by p53 (PMID:19652226, PMID:24304549, PMID:21937108, PMID:34565269, PMID:34577642, PMID:40056047). Two promoters (P1 and P2) provide tissue-selective output, with P2 preferred in placenta (PMID:21937108, PMID:34565269).

Mechanistic history

Synthesis pass · year-by-year structured walk · 29 steps
  1. 2000 Medium

    Established PLAC1 as a placenta-specific secreted protein structurally related to the ZP domain family, framing it as a potential matrix/interaction module rather than an enzyme.

    Evidence cDNA/genomic sequencing, ZP3 homology analysis, and in situ hybridization in mouse embryos

    PMID:10995572

    Open questions at the time
    • No direct functional validation of the inferred ZP3-like interaction
    • Binding partners unknown at this stage
  2. 2006 High

    Demonstrated that the PLAC1-homologous ZP-N subdomain is a self-contained folding unit with native disulfide connectivity capable of filament assembly, giving PLAC1 a structural rationale for protein-protein assembly.

    Evidence Recombinant ZP3 ZP-N expression, mass spectrometry disulfide mapping, and electron microscopy of filaments

    PMID:16600035

    Open questions at the time
    • Done on ZP3 not PLAC1 itself
    • Does not establish PLAC1's in vivo polymerization or binding targets
  3. 2002 Medium

    Showed PLAC1 is trophoblast-exclusive and growth-factor responsive, linking it to FGF7/KGF signaling rather than IGF-II.

    Evidence Northern, qRT-PCR, in situ hybridization, and growth factor treatment of BeWo cells

    PMID:12412044

    Open questions at the time
    • Magnitude of induction modest
    • Mechanism of FGF7 responsiveness unresolved
  4. 2005 Medium

    Placed FGF7-induced PLAC1 expression downstream of MAPK and PI3K signaling during cytotrophoblast differentiation, tying it to syncytialization.

    Evidence qRT-PCR with PD-98059 and wortmannin inhibition in a differentiation culture model

    PMID:15803460

    Open questions at the time
    • Pharmacological inhibitors lack target specificity
    • Does not identify direct transcriptional effectors
  5. 2007 High

    Localized PLAC1 to intracellular membranes and the apical microvillous membrane of the syncytiotrophoblast, defining its subcellular compartment.

    Evidence Subcellular fractionation immunoblot plus immunofluorescence microscopy of placenta

    PMID:17186554

    Open questions at the time
    • Functional consequence of apical localization not tested
    • Topology and orientation in membrane unresolved
  6. 2009 High

    Defined the core transcriptional control of PLAC1 in cancer cells as SP1 plus C/EBPβ-2, with ERα acting through non-classical tethering.

    Evidence DNA affinity precipitation, ChIP, and promoter-reporter assays

    PMID:19652226

    Open questions at the time
    • Does not address placental transcriptional control
    • Promoter usage (P1 vs P2) not distinguished
  7. 2011 Medium

    Revealed a dual-promoter (P1/P2) architecture with tissue-selective usage and RXR/LXR responsiveness, explaining differential expression in placenta versus tumors.

    Evidence Gene structure analysis and luciferase reporter assays with nuclear receptor overexpression

    PMID:21937108

    Open questions at the time
    • Endogenous promoter switching mechanism unclear
    • Direct nuclear receptor binding sites not mapped
  8. 2012 High

    Genetic ablation in mice established PLAC1 as a regulator of placental size and trophoblast layer organization and revealed paternal imprinting with partial X-inactivation escape.

    Evidence Plac1 knockout mouse with placental/embryo weight, histology, and imprinting analysis

    PMID:22729990

    Open questions at the time
    • Molecular mechanism of spongiotrophoblast expansion not defined
    • Direct effector pathways untested
  9. 2013 Medium

    Extended PLAC1 transcriptional regulation to opposing p53/RB control and confirmed nuclear receptor activation of the P1 promoter, linking derepression to oncogenic transformation.

    Evidence SV40 T antigen transformation of fibroblasts with Tp53/RB and RXR/LXR manipulation

    PMID:23999628

    Open questions at the time
    • Direct p53 binding to promoter not yet shown here
    • Cell-type generality unclear
  10. 2013 High

    Identified NCOA3 as the selective and required coactivator for ERα-driven PLAC1 transactivation in breast cancer.

    Evidence ChIP, NCOA3 RNAi knockdown, and estradiol rescue in MCF-7 cells

    PMID:24304549

    Open questions at the time
    • Coactivator role in placenta untested
    • Does not address non-ERα contexts
  11. 2013 High

    Showed PLAC1 expression extends to multiple fetal tissues and that ablation causes lethal hydrocephalus, establishing a non-redundant role beyond the placenta.

    Evidence Knockout mouse with ISH, β-galactosidase reporter, and immunohistochemistry

    PMID:24014101

    Open questions at the time
    • Mechanism linking PLAC1 loss to hydrocephalus unknown
    • Whether brain phenotype is secondary to placental dysfunction unresolved
  12. 2015 High

    Complementation rescue demonstrated that PLAC1 dosage—not mere presence—governs normal placentation, with both loss and excess causing hyperplasia.

    Evidence Lentiviral Plac1 transgene complementation in KO mice with comparative histology

    PMID:26586843

    Open questions at the time
    • Junctional zone hyperplasia not fully rescued
    • Dose-response molecular mediators undefined
  13. 2016 Medium

    Direct knockdown in primary trophoblasts established PLAC1 as required for human syncytialization, connecting expression dynamics to cell fusion.

    Evidence siRNA knockdown with cell fusion index and syncytialization marker analysis in primary CTBs

    PMID:27692364

    Open questions at the time
    • Molecular fusion machinery link unidentified
    • Single primary-cell model
  14. 2016 Medium

    Placed PLAC1 upstream of AKT signaling in cancer, driving proliferation, cell-cycle progression, and EMT.

    Evidence siRNA knockdown in HCC cells with proliferation, cell-cycle, apoptosis, EMT marker, and p-Akt readouts

    PMID:27878289

    Open questions at the time
    • Direct upstream receptor not identified in this study
    • Correlative pathway markers without reconstitution
  15. 2017 Medium

    Demonstrated that surface PLAC1 undergoes rapid antibody-triggered internalization, indicating receptor-like endocytic behavior relevant to targeted therapy.

    Evidence Anti-PLAC1 antibody internalization kinetics by flow cytometry on prostate cancer cells

    PMID:29042604

    Open questions at the time
    • Endogenous internalization signal unknown
    • Physiological internalization stimulus not defined
  16. 2017 Medium

    Mapped the spatiotemporal embryonic expression of Plac1 across trophoblast subtypes and showed knockdown retards trophoblast stem cell differentiation.

    Evidence In situ hybridization and shRNA knockdown in trophoblast stem cell differentiation

    PMID:29055961

    Open questions at the time
    • Differentiation-stage-specific targets unresolved
    • Mechanistic link to subtype specification missing
  17. 2017 Low

    Clarified that PLAC1's native signal peptide directs it to submembranous compartments, implying cancer cells use distinct signals for surface display.

    Evidence Heterologous expression and immunolocalization in CHO-K1 cells

    PMID:32153735

    Open questions at the time
    • Single localization experiment in heterologous system with no functional consequence established
    • Cancer-specific surface-targeting signal not identified
  18. 2018 High

    Identified Furin as a direct PLAC1 partner driving Notch1-NICD generation and PTEN suppression, defining a concrete pro-invasive signaling axis.

    Evidence Reciprocal Co-IP, immunofluorescence, microarray, Furin-inhibitor/PTEN-overexpression rescue, and in vivo metastasis assay in MDA-MB-231 cells

    PMID:29704427

    Open questions at the time
    • Whether the same axis operates in trophoblasts not tested here
    • Structural basis of PLAC1-Furin binding unresolved
  19. 2018 High

    Showed PLAC1 drives tumor growth in an adaptive-immunity-dependent manner via a CXCL1 chemokine axis, adding an immune-modulatory function.

    Evidence RNAi knockdown with syngeneic vs SCID tumor implantation, expression profiling, and Cxcl1 rescue in EO771 cells

    PMID:29632317

    Open questions at the time
    • Direct molecular link from PLAC1 to Cxcl1 induction undefined
    • Mouse-specific immune readouts
  20. 2020 Medium

    Defined PLAC1 as a secreted ECM-associated co-ligand forming a trimeric FGF7/FGFR2IIIb complex that activates AKT, providing the receptor context for its proliferative signaling.

    Evidence Secretion/ECM adherence and trimeric complex formation assays with AKT phosphorylation readouts in cancer cell lines

    PMID:32499871

    Open questions at the time
    • Stoichiometry and structure of the trimeric complex unresolved
    • Whether trophoblast signaling uses the same complex untested
  21. 2021 High

    Identified Desmoglein-2 as a direct PLAC1 binding partner and pinpointed the ZP-N cysteines as essential for the interaction, connecting PLAC1 to desmosomal membrane biology.

    Evidence IP-mass spectrometry, co-transfection IP, and ZP-N cysteine site-directed mutagenesis

    PMID:34118612

    Open questions at the time
    • Functional outcome of PLAC1-DSG2 binding in trophoblasts not established
    • Whether binding affects desmosome integrity untested
  22. 2021 Medium

    Linked reduced PLAC1 to preeclampsia and identified the hypoxia-sensitive MED1-TRAP coactivator acting through the P2 promoter as a driver of expression.

    Evidence Promoter-specific qPCR of placental tissue, DMOG treatment, and MED1-PLAC1 correlation in HTR8/SVneo cells

    PMID:34565269

    Open questions at the time
    • Direct MED1 binding to P2 not demonstrated
    • Causal role of PLAC1 loss in preeclampsia onset unresolved
  23. 2021 Medium

    Established p53 as a direct transcriptional suppressor of PLAC1, explaining its derepression in TP53-mutant cancers.

    Evidence p53 reactivator HO-3867 treatment of TP53-mutant ovarian cancer cells with expression and phenotype readouts

    PMID:34577642

    Open questions at the time
    • Direct p53 promoter occupancy not mapped here
    • Off-target effects of HO-3867 possible
  24. 2021 Medium

    Confirmed a protective, proliferation/invasion-promoting role for PLAC1 in trophoblasts under hypoxic stress through knockdown and overexpression rescue.

    Evidence siRNA knockdown, overexpression rescue, and functional assays under hypoxia in trophoblast cells

    PMID:33941557

    Open questions at the time
    • Downstream effectors of protection not identified
    • Single-lab functional assays
  25. 2021 Medium

    Replicated the Furin/NICD/PTEN axis in nasopharyngeal carcinoma, generalizing the PLAC1-Furin mechanism beyond breast cancer.

    Evidence Co-IP and Furin-overexpression rescue with functional assays in NPC cells

    PMID:33418237

    Open questions at the time
    • No structural detail of interaction
    • Single-lab confirmation
  26. 2024 Medium

    Defined the mTOR/HIF-1α/Snail axis as a downstream effector of PLAC1-driven cervical cancer invasion, with HIF-1α as a required mediator.

    Evidence Overexpression/knockdown with mTOR pharmacology, HIF1A siRNA rescue, and xenografts in CCa lines

    PMID:39549936

    Open questions at the time
    • Direct molecular link from PLAC1 to mTOR activation undefined
    • Single-lab study
  27. 2025 Medium

    Integrated PLAC1 into a reciprocal pro-tumor loop in HNSCC—promoting EGFR recycling/PI3K-AKT and reshaping the T-cell/Treg microenvironment—and confirmed SP1 as a direct transcriptional regulator.

    Evidence CUT&Tag-seq for SP1, in vivo and autochthonous tumor models, and single-cell/bulk RNA-seq integration

    PMID:40056047

    Open questions at the time
    • Direct PLAC1-EGFR molecular interaction not resolved
    • Causality of each immune ligand arm not individually dissected
  28. 2026 High

    A genome-edited rat model and species comparison refined PLAC1 function, showing it regulates invasive trophoblasts in rats but acts mainly through syncytiotrophoblast differentiation in humans, with furin as a conserved mechanistic link.

    Evidence Plac1 mutant rat with histology and trophoblast differentiation assays plus human trophoblast comparison

    PMID:42007670

    Open questions at the time
    • Molecular basis of species divergence unresolved
    • How furin link integrates with syncytialization unclear
  29. 2026 Medium

    Transcriptomic profiling of Plac1 KO placentas linked PLAC1 loss to disrupted Rho GTPase/actin and canonical developmental signaling and to a preeclampsia-like signature.

    Evidence Microarray with GO/KEGG/IPA pathway analysis of KO mouse placentas (preprint)

    PMID:42244670

    Open questions at the time
    • No direct mechanistic validation of individual pathway interactions
    • Correlative transcriptomics only

Open questions

Synthesis pass · forward-looking unresolved questions
  • How PLAC1's ZP-N-dependent membrane partner interactions (DSG2) and its dual roles as an FGFR co-ligand and Furin-binding intracellular effector are reconciled into a single physical mechanism that controls syncytialization remains unresolved.
  • No structure of PLAC1 or its complexes
  • Topology reconciling secreted/ECM, surface, and intracellular pools undefined
  • Direct link between transcriptional regulators and downstream effector choice unmapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 2 GO:0098772 molecular function regulator activity 2 GO:0048018 receptor ligand activity 1
Localization
GO:0005886 plasma membrane 3 GO:0005576 extracellular region 1 GO:0005783 endoplasmic reticulum 1 GO:0005829 cytosol 1 GO:0031012 extracellular matrix 1
Pathway
R-HSA-1643685 Disease 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-1266738 Developmental Biology 3 R-HSA-162582 Signal Transduction 3 R-HSA-168256 Immune System 2
Partners
CEBPBDSG2FGF7FGFR2FURINMED1NCOA3SP1
Complex memberships
PLAC1-FGF7-FGFR2IIIb trimeric complex

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 PLAC1 protein contains a signal peptide and a peptide sequence homologous to an interaction domain of ZP3 (zona pellucida 3) protein, suggesting structural and functional relationship with the ZP domain family. cDNA sequencing, genomic sequencing, sequence homology analysis; in situ hybridization in mouse embryos Genomics Medium 10995572
2006 The PLAC1-homology region (ZP-N subdomain) of ZP3 is sufficient for polymerization into filaments; the four conserved Cys residues within ZP-N adopt the same disulfide bond connectivity as in full-length native ZP3, indicating correct folding. This establishes that ZP-N is a biologically active folding unit and that PLAC1-like proteins share a module capable of filament assembly. Recombinant expression of ZP3 ZP-N fused to maltose-binding protein in engineered bacteria; mass spectrometry to confirm disulfide bonds; electron microscopy and biochemical analyses of filament assembly BMC biochemistry High 16600035
2002 PLAC1 mRNA is expressed exclusively in trophoblastic cells throughout gestation (8–41 weeks) in human placenta. Keratinocyte growth factor (KGF/FGF7) stimulates steady-state PLAC1 mRNA expression approximately twofold in BeWo choriocarcinoma cells, with stimulation only after 24 h exposure; IGF-II had no effect. Northern analysis, quantitative real-time PCR, in situ hybridization with 35S-labeled riboprobe; growth factor treatment of BeWo cells Molecular reproduction and development Medium 12412044
2005 PLAC1 mRNA increases more than 300-fold during cytotrophoblast differentiation into syncytiotrophoblasts in culture. FGF-7-stimulated PLAC1 expression is significantly inhibited by PD-98059 (MEK inhibitor) and wortmannin (PI3K inhibitor), indicating mediation via MAP kinase and PI3K-dependent signaling pathways. EGF alone had no effect on PLAC1 expression but potentiated FGF-7-induced expression. Quantitative RT-PCR; pharmacological inhibition with PD-98059 and wortmannin; cytotrophoblast differentiation culture model Molecular reproduction and development Medium 15803460
2007 The PLAC1 protein localizes specifically to intracellular membranous compartments and the apical microvillous membrane (MVM) of the differentiated syncytiotrophoblast. A 30 kDa band was detected in the microsomal fraction but not in mitochondrial, nuclear, or soluble fractions. PLAC1 immunoreactivity was detected only in MVM fractions, not in basal membrane fractions. Immunohistochemistry, deconvolution immunofluorescence microscopy, immunoblot analysis of subcellular fractions (nuclear, mitochondrial, microsomal, soluble, MVM, BM) Molecular reproduction and development High 17186554
2009 Basal PLAC1 promoter activity in breast cancer cells is selectively controlled by SP1 and isoform 2 of C/EBPβ (CCAAT/enhancer-binding protein beta-2), both of which must bind their respective elements for full promoter activity. Ligand-activated ERα further augments PLAC1 transcription via a non-classical pathway independent of estrogen-response elements, by tethering to DNA-bound C/EBPβ-2 and SP1. DNA affinity precipitation, chromatin immunoprecipitation (ChIP), promoter-reporter assays, transfection The Journal of biological chemistry High 19652226
2011 PLAC1 gene has two promoters (P1 and P2) separated by 105 kb. Both P1 and P2 are activated by RXRα in conjunction with LXRα or LXRβ. In placenta, P2 is the preferred promoter, whereas tumor cell lines preferentially use either P1 or P2. Luciferase reporter assays confirmed that the endogenously more active promoter is preferentially transcribed. Gene structure analysis, luciferase reporter assays with P1 and P2 fused to reporter in cancer cell lines, nuclear receptor overexpression Placenta Medium 21937108
2012 Plac1 ablation in mice causes placentomegaly (~100% increase in placental weight at E16.5) and mild intrauterine growth retardation (~7–12% reduction in embryo weight). Histologically, mutants exhibit an expanded spongiotrophoblast layer that invades the labyrinth. Plac1 is paternally imprinted; the paternal allele partially escapes X-inactivation and contributes to placental growth regulation. Male Plac1 KO mice exhibit decreased postnatal viability. Knockout mouse model; placental and embryo weight measurements; histological analysis; quantitative real-time PCR for imprinting analysis Molecular reproduction and development High 22729990
2013 SV40 T antigen derepresses the PLAC1 P1 promoter in primary fibroblasts; Tp53 and RB exert critical and opposing actions on PLAC1 P1 promoter activity, and nuclear receptors RXR and LXR sharply increase expression level. T antigen transformation of normal fibroblasts; promoter activity assays; genetic manipulation of Tp53 and RB Oncogenesis Medium 23999628
2013 NCOA3, but not NCOA1 or NCOA2, is selectively recruited to the PLAC1 promoter in ERα-positive MCF-7 breast cancer cells. RNAi-mediated silencing of NCOA3 markedly decreases PLAC1 expression, and estradiol treatment cannot restore PLAC1 expression in NCOA3-depleted cells, demonstrating that NCOA3 is required for ERα-mediated PLAC1 transactivation. Chromatin immunoprecipitation (ChIP), RNAi knockdown, qRT-PCR, Western blot, ERα activation assays BMC cancer High 24304549
2013 Plac1 is expressed throughout the developing fetus (brain, lungs, kidney, intestine, liver, heart) in a developmentally regulated manner. Plac1 mRNA localizes to hindbrain and lateral ventricles. The Plac1 protein localizes to the apical surface of epithelial cells lining developing airways of the lung and proximal renal tubules. Plac1 ablation is associated with lethal hydrocephalus in 20% of KO males and 10–15% of mutant-allele females, demonstrating a non-redundant role in brain development. Knockout mouse model; quantitative real-time PCR; in situ hybridization; β-galactosidase reporter expression; immunohistochemistry Birth defects research. Part A, Clinical and molecular teratology High 24014101
2015 Lentiviral vector-mediated Plac1 transgene expression in the Plac1-null placenta rescued fetal development and morphology of maternal blood sinuses in the labyrinth zone, but placental hyperplasia remained with an expanded junctional zone. Wild-type placentas with transgenically expressed Plac1 also exhibited placental hyperplasia, indicating that Plac1 is involved in trophoblast cell proliferation, differentiation, and migration, and its proper expression level is required for normal placentation. Lentiviral vector-mediated complementation in Plac1 knockout mice; placental morphology and histological analysis; comparison of KO, complemented, and WT with transgene Biology of reproduction High 26586843
2016 PLAC1 is involved in human trophoblast syncytialization: its expression is significantly elevated during syncytialization, and siRNA-mediated knockdown of PLAC1 in primary term cytotrophoblasts attenuates spontaneous syncytialization as indicated by reduced cell fusion index and altered expression of syncytialization markers. In situ hybridization, immunohistochemistry, real-time RT-PCR, Western blot, siRNA knockdown in primary CTBs, cell fusion index measurement Reproductive biology Medium 27692364
2016 PLAC1 knockdown by siRNA in HCC cells (Bel-7402 and HepG2) decreases proliferation, increases apoptosis, induces G1 cell cycle arrest through suppression of cyclin D1 and CDK4, and represses epithelial-mesenchymal transition (EMT) with decreased migration and invasion. Decreased Plac1 expression attenuated phosphorylation of Akt, placing PLAC1 upstream of Akt signaling. siRNA knockdown; CCK-8 proliferation assay; flow cytometry for apoptosis and cell cycle; Western blot for cyclin D1, CDK4, E-cadherin, vimentin, twist, snail, p-Akt; migration and invasion assays Oncology reports Medium 27878289
2017 PLAC1 protein localizes to the cytoplasm and plasma membrane in cancer cells. When expressed with its own signal peptide in CHO-K1 cells, PLAC1 is targeted to submembranous but not surface compartments, suggesting that cancer cells utilize unknown localization signals for surface expression of PLAC1. Cloning into expression vectors; RT-PCR, Western blot, immunocytochemistry, immunofluorescence, flow cytometry in transfected CHO-K1 cells; chimeric TFR1-PLAC1 construct approach Avicenna journal of medical biotechnology Low 32153735
2018 PLAC1 physically interacts with Furin (proprotein convertase) as demonstrated by co-immunoprecipitation and immunofluorescence. This interaction leads to Notch1 processing and generation of Notch1 intracellular domain (NICD), which inhibits PTEN activity, promoting breast cancer invasion and metastasis. Inhibition of Furin or overexpression of PTEN in Plac1-overexpressing cells blocked Plac1-induced tumor cell progression. Co-immunoprecipitation, immunofluorescence, overexpression/knockdown in MDA-MB-231 cells, microarray gene expression profiling, rescue experiments with Furin inhibitor and PTEN overexpression, in vivo metastasis model Molecular oncology High 29704427
2018 Plac1 knockdown in EO771 mammary carcinoma cells reduces proliferation in vitro by 50% and impairs tumor growth in syngeneic (immunocompetent) but not SCID mice, indicating adaptive immunity dependence. Gene expression profiling revealed reduction in inflammatory and immune factors including Cxcl1, Ccl5, Ly6a/Sca-1, Ly6c, and Lif upon Plac1 KD. Cxcl1 knockdown phenocopied Plac1 KD, and overexpression of Cxcl1 partially rescued Plac1 KD cells, placing PLAC1 upstream of Cxcl1 in the chemokine axis modulating tumor immune evasion. RNAi knockdown; in vitro proliferation assay; syngeneic vs. SCID mouse tumor implantation; gene expression profiling; CXCR2 antagonist treatment; immune cell phenotyping; Cxcl1 rescue experiment Scientific reports High 29632317
2020 PLAC1 is secreted and adheres to the extracellular matrix, where it forms a trimeric complex with FGF7 and FGFR2IIIb. PLAC1 signaling via FGFR2IIIb activates AKT phosphorylation in cancer cell lines, establishing PLAC1 as a co-receptor/ligand in the FGF signaling pathway essential for FGF7/FGFRIIIb-induced Akt-mediated cancer cell proliferation. Localization studies (secretion and ECM adherence assays), receptor-ligand interaction assays (trimeric complex formation), AKT phosphorylation assays in choriocarcinoma and breast cancer cell lines Oncotarget Medium 32499871
2021 PLAC1 directly interacts with Desmoglein-2 (DSG2), a component of the desmosomal membrane complex. Mutations of cysteine residues in the ZP-N domain of PLAC1 disrupt the interaction between PLAC1 and DSG2, identifying the ZP-N domain cysteines as critical for this binding. Cell fractionation, immunoprecipitation, mass spectrometry to identify interaction partners; co-transfection with PLAC1 and DSG2 followed by immunoprecipitation; site-directed mutagenesis of ZP-N cysteine residues Placenta High 34118612
2021 PLAC1 expression is significantly decreased in trophoblasts under hypoxic conditions. PLAC1 knockdown inhibits trophoblast proliferation, migration, and invasion and increases apoptosis. Overexpression of PLAC1 can reverse hypoxia-induced reduction in trophoblast cell viability and inhibit apoptosis, indicating a protective role against hypoxia-induced damage. siRNA knockdown; CCK-8 proliferation assay; wound healing and Transwell assays; flow cytometry for apoptosis; hypoxia treatment (low oxygen concentration); PLAC1 overexpression rescue Annals of clinical and laboratory science Medium 33941557
2021 PLAC1 downregulation suppresses trophoblast proliferation, migration, and invasion of NPC cells, and co-IP confirmed interaction between Plac1 and Furin. Overexpression of Furin reversed the inhibitory effects of PLAC1 silencing, confirming the Furin/NICD/PTEN pathway as a downstream effector of PLAC1 in NPC cells. Co-immunoprecipitation, siRNA knockdown, overexpression, CCK-8 assay, colony formation, scratch assay, Transwell assay, qRT-PCR, Western blot Tissue & cell Medium 33418237
2021 PLAC1 expression is significantly downregulated in preeclampsia and this reduction is driven through the P2 (proximal) PLAC1 promoter. MED1 (mediator complex subunit 1), a hypoxia-sensitive transcription coactivator, expression is significantly correlated with PLAC1 expression (r²=0.607), and the hypoxia mimic DMOG suppresses PLAC1 transcription in trophoblast cells, identifying the MED1-TRAP cofactor complex as a hypoxia-sensitive driver of PLAC1 expression. qPCR of placental tissue (PE vs. controls), promoter-specific qPCR, DMOG treatment of HTR8/SVneo trophoblast cells, correlation analysis of MED1 and PLAC1 expression The journal of maternal-fetal & neonatal medicine Medium 34565269
2021 p53 directly suppresses PLAC1 transcription; missense mutations in TP53 lead to loss of PLAC1 transcriptional suppression. Treatment of TP53-mutant ovarian cancer cells with the p53 reactivator HO-3867 rescued PLAC1 transcriptional suppression and inhibited cell proliferation while increasing apoptosis. Treatment of OVCAR3 and ES-2 cells (harboring TP53 missense mutations) with HO-3867; measurement of PLAC1 expression, cell proliferation, and apoptosis Pharmaceuticals Medium 34577642
2024 PLAC1 promotes cervical cancer cell proliferation, migration, and invasion via the mTOR/HIF-1α/Snail signaling pathway. In vivo, PLAC1 silencing reduced tumor growth, and this effect could be rescued by HIF1A siRNA reversal, confirming HIF-1α as a downstream effector of PLAC1-mediated tumorigenesis. PLAC1 overexpression/knockdown in CCa cell lines; cell cycle and apoptosis analysis; functional migration/invasion assays; mTOR activator (MHY1485) and inhibitor (rapamycin) pharmacological validation; HIF1A siRNA; xenograft nude mouse model Life sciences Medium 39549936
2025 Plac1 expression promotes HNSCC progression by inducing EGFR endocytosis and recycling to increase PI3K/AKT signaling pathway activity. Plac1+ tumor cells recruit CD4+ T cells via CXCL11/CXCR3 and induce Treg differentiation via PVR/TIGIT, while Tregs in turn activate tumorigenic signaling in Plac1+ cells via LTA/LTBR, forming a reciprocal pro-tumor loop. SP1 was identified as a specific transcriptional regulator of Plac1 confirmed by CUT&Tag-seq. CUT&Tag-seq for SP1 binding; in vitro experiments; in vivo subcutaneous tumor model; transgenic autochthonous tumor model; single-cell and bulk RNA-seq integration Advanced science Medium 40056047
2026 In rats, Plac1 is expressed in the junctional zone and invasive trophoblast cells; Plac1 mutant rats exhibit placentomegaly with expanded junctional zone, irregular junctional zone-labyrinth boundary, deficiency of intrauterine invasive trophoblast cells, and NK cell infiltration at late gestation. In humans, PLAC1 contributes minimally to invasive/extravillous trophoblast regulation but instead acts through syncytiotrophoblast differentiation. In both rat and human trophoblast cells, PLAC1 function is mechanistically linked to furin. Genome-edited Plac1 mutant rat model; trophoblast cell differentiation assays; histological analysis; comparison with human trophoblast cell models Development (Cambridge, England) High 42007670
2026 Plac1 ablation in mice disrupts expression of genes enriched for Rho GTPase-mediated and actin cytoskeleton-based processes as well as canonical signaling pathways (Integrin, GPCR, Wnt, Notch, VEGF, BMP, TGF-β) important for trophoblast development and vascular function. Upregulated genes reflect immune activation and oxidative stress responses. A preeclampsia transcriptomic-associated signature was induced in Plac1 KO placentas and strengthened over time. Plac1 KO mouse model; gene expression microarray at E16.5 and E18.5; GO, KEGG, and IPA pathway analyses bioRxivpreprint Medium 42244670
2017 PLAC1 binding to anti-PLAC1 antibody on prostate cancer cell surfaces induces rapid internalization within minutes, reaching ~50% internalization after 15 min and near-complete internalization within 1 hour, demonstrating receptor-mediated endocytosis of surface PLAC1. Antibody internalization assay (anti-PLAC1 antibody 2H12C12) measured by flow cytometry/quantification on prostate cancer cells Scientific reports Medium 29042604
2017 Plac1 mRNA in mouse embryos is expressed at the fetomaternal interface exclusively in the ectoplacental cone at 7.5–9.5 dpc, then abundantly in the spongiotrophoblast and moderately in the labyrinth until 13.5 dpc. Plac1 is also expressed in secondary trophoblast giant cells and glycogen trophoblast cells but not in primary trophoblast giant cells. Plac1 knockdown in trophoblast stem cells retards differentiation into trophoblast subpopulations. In situ hybridization; trophoblast stem cell differentiation model with shRNA-lentivirus knockdown; real-time RT-PCR Cellular physiology and biochemistry Medium 29055961

Source papers

Stage 0 corpus · 68 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 PLAC1, an Xq26 gene with placenta-specific expression. Genomics 93 10995572
2007 PLAC1, a trophoblast-specific cell surface protein, is expressed in a range of human tumors and elicits spontaneous antibody responses. Cancer immunity 68 17983203
2006 The PLAC1-homology region of the ZP domain is sufficient for protein polymerisation. BMC biochemistry 65 16600035
2012 Plac1 (placenta-specific 1) is essential for normal placental and embryonic development. Molecular reproduction and development 64 22729990
2007 Cell-free mRNA concentrations of CRH, PLAC1, and selectin-P are increased in the plasma of pregnant women with preeclampsia. Prenatal diagnosis 61 17554801
2008 Plac1 is a tumor-specific antigen capable of eliciting spontaneous antibody responses in human cancer patients. International journal of cancer 52 18183594
2002 PLAC1, a trophoblast-specific gene, is expressed throughout pregnancy in the human placenta and modulated by keratinocyte growth factor. Molecular reproduction and development 46 12412044
2010 PLAC1 (Placenta-specific 1): a novel, X-linked gene with roles in reproductive and cancer biology. Prenatal diagnosis 42 20509147
2018 Cancer/testis antigen-Plac1 promotes invasion and metastasis of breast cancer through Furin/NICD/PTEN signaling pathway. Molecular oncology 40 29704427
2005 PLAC1 expression increases during trophoblast differentiation: evidence for regulatory interactions with the fibroblast growth factor-7 (FGF-7) axis. Molecular reproduction and development 38 15803460
2007 The PLAC1 protein localizes to membranous compartments in the apical region of the syncytiotrophoblast. Molecular reproduction and development 35 17186554
2017 Placenta-specific1 (PLAC1) is a potential target for antibody-drug conjugate-based prostate cancer immunotherapy. Scientific reports 30 29042604
2009 Selective activation of trophoblast-specific PLAC1 in breast cancer by CCAAT/enhancer-binding protein beta (C/EBPbeta) isoform 2. The Journal of biological chemistry 29 19652226
2006 Increased plasma mRNAs of placenta-specific 1 (PLAC1) and glial cells-missing 1 (GCM1) in mothers with pre-eclampsia. Hiroshima journal of medical sciences 27 16594548
2019 PLAC1: biology and potential application in cancer immunotherapy. Cancer immunology, immunotherapy : CII 26 31165204
2013 NCOA3 is a selective co-activator of estrogen receptor α-mediated transactivation of PLAC1 in MCF-7 breast cancer cells. BMC cancer 26 24304549
2018 Placental expression of PAPPA, PAPPA-2 and PLAC-1 in pregnacies is associated with FGR. Molecular medicine reports 24 29532882
2011 Identification of a novel HLA-A2-restricted cytotoxic T lymphocyte epitope from cancer-testis antigen PLAC1 in breast cancer. Amino acids 24 21710262
2018 PLAC1-specific TCR-engineered T cells mediate antigen-specific antitumor effects in breast cancer. Oncology letters 21 29556312
2018 PLAC1 as a serum biomarker for breast cancer. PloS one 20 29432428
2016 Oncogenic function of Plac1 on the proliferation and metastasis in hepatocellular carcinoma cells. Oncology reports 20 27878289
2011 RXRα and LXR activate two promoters in placenta- and tumor-specific expression of PLAC1. Placenta 20 21937108
2014 The placental specific gene, PLAC1, is induced by the Epstein-Barr virus and is expressed in human tumor cells. Virology journal 19 24912876
2011 Plasma mRNA concentrations of placenta-specific 1 (PLAC1) and pregnancy associated plasma protein A (PAPP-A) are higher in early-onset than late-onset pre-eclampsia. The journal of obstetrics and gynaecology research 19 21392164
2015 Lentiviral Vector-Mediated Complementation Restored Fetal Viability but Not Placental Hyperplasia in Plac1-Deficient Mice. Biology of reproduction 17 26586843
2014 The nexus of prematurity, birth defects, and intrauterine growth restriction: a role for plac1-regulated pathways. Frontiers in pediatrics 17 24600606
2013 Preliminary evidence for high anti-PLAC1 antibody levels in infertile patients with repeated unexplained implantation failure. Placenta 16 23434395
2018 Plac1 Is a Key Regulator of the Inflammatory Response and Immune Tolerance In Mammary Tumorigenesis. Scientific reports 15 29632317
2013 Identification of two new HLA-A*0201-restricted cytotoxic T lymphocyte epitopes from colorectal carcinoma-associated antigen PLAC1/CP1. Journal of gastroenterology 15 23604623
2021 Plac1 promotes nasopharyngeal carcinoma cells proliferation, migration and invasion via Furin/NICD/PTEN pathway. Tissue & cell 13 33418237
2017 Optimized protocol for soluble prokaryotic expression, purification and structural analysis of human placenta specific-1(PLAC1). Protein expression and purification 13 28315746
2016 PLAC1 is involved in human trophoblast syncytialization. Reproductive biology 13 27692364
2013 Plac1 (placenta-specific 1) is widely expressed during fetal development and is associated with a lethal form of hydrocephalus. Birth defects research. Part A, Clinical and molecular teratology 13 24014101
2005 Rapid clearance of mRNA for PLAC1 gene in maternal blood after delivery. Fetal diagnosis and therapy 13 15608456
2021 The Synthetic Curcumin Analog HO-3867 Rescues Suppression of PLAC1 Expression in Ovarian Cancer Cells. Pharmaceuticals (Basel, Switzerland) 11 34577642
2019 In silico Evaluation of PLAC1-fliC As a Chimeric Vaccine against Breast Cancer. Iranian biomedical journal 11 31952435
2013 T antigen transformation reveals Tp53/RB-dependent route to PLAC1 transcription activation in primary fibroblasts. Oncogenesis 11 23999628
2020 PLAC1 is essential for FGF7/FGFRIIIb-induced Akt-mediated cancer cell proliferation. Oncotarget 10 32499871
2019 Declined placental PLAC1 expression is involved in preeclampsia. Medicine 10 31689783
2014 Circulating mRNA for the PLAC1 gene as a second trimester marker (14-18 weeks' gestation) in the screening for late preeclampsia. Fetal diagnosis and therapy 10 25138310
2010 Characterization of pLAC1, a cryptic plasmid isolated from Lactobacillus acidipiscis and comparative analysis with its related plasmids. International journal of food microbiology 9 20538362
2022 Plac1 Remodels the Tumor Immune Evasion Microenvironment and Predicts Therapeutic Response in Head and Neck Squamous Cell Carcinoma. Frontiers in oncology 7 35814442
1989 Staphylococcus aureus chromosomal mutation plaC1 amplifies plasmid pT181 by depressing synthesis of its negative-effector countertranscripts. Journal of bacteriology 7 2788645
2021 PLAC1 Regulates the Occurrence of Fetal Growth Restriction by Inhibiting the Apoptosis of Trophoblast Cells. Annals of clinical and laboratory science 6 33941557
2021 PLAC1 affects cell to cell communication by interacting with the desmosome complex. Placenta 6 34118612
2020 Discovery of a potential biomarker for immunotherapy of melanoma: PLAC1 as an emerging target. Immunopharmacology and immunotoxicology 6 33106058
2006 PLAC1 mRNA levels in maternal blood at induction of labor correlate negatively with induction-delivery interval. European journal of obstetrics, gynecology, and reproductive biology 6 16860456
2025 Plac1+ Tumor Cell-Treg Interplay Supports Tumorigenesis and Progression of Head and Neck Cancer. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 5 40056047
2023 Differential expression of PLAC1 and Netrin-1 in liver metastasis of colorectal cancer and its predictive value. BMC gastroenterology 5 37568074
2022 Immunization with placenta-specific 1 (plac1) induces potent anti-tumor responses and prolongs survival in a mouse model of melanoma. Advances in medical sciences 5 36084365
2019 Expression profiling of plac1 in murine cancer cell lines. Experimental oncology 5 30932401
2017 Plac1 Expression Pattern at the Mouse Fetomaternal Interface and Involvement in Trophoblast Differentiation. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 5 29055961
2013 PLAC1 Expression Decreases in Chorionic Villi in Response to Labor. ISRN obstetrics and gynecology 5 23840959
2024 PLAC1 augments the malignant phenotype of cervical cancer through the mTOR/HIF-1α/Snail signaling pathway. Life sciences 4 39549936
2023 The Oncogenic Theory of Preeclampsia: Is Amniotic Mesenchymal Stem Cells-Derived PLAC1 Involved? International journal of molecular sciences 4 36835024
2010 [Expression of PLAC1/CP1 genes in primary colorectal carcinoma and its clinical significance]. Zhonghua bing li xue za zhi = Chinese journal of pathology 3 21215095
2024 Identification of placenta-specific protein 1 (PLAC-1) expression on human PC-3 cell line-derived prostate cancer stem cells compared to the tumor parental cells. Discover oncology 2 38943028
2021 Placenta-specific protein 1 (PLAC1) expression is significantly down-regulated in preeclampsia via a hypoxia-mediated mechanism. The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians 2 34565269
2018 Association of Higher Maternal Serum Levels of Plac1 Protein with Intrauterine Growth Restriction. Zeitschrift fur Geburtshilfe und Neonatologie 2 30267394
2024 Production and characterization of a panel of anti-mouse placenta-specific protein 1 (plac1) monoclonal antibodies. Analytical biochemistry 1 39332465
2022 Optimization of Expression and Purification of Recombinant Mouse plac1. Avicenna journal of medical biotechnology 1 35509359
2020 Expression of Human Placenta-specific 1 (PLAC1) in CHO-K1 Cells. Avicenna journal of medical biotechnology 1 32153735
2017 PLAC1 immunization does not induce infertility in mice. Immunotherapy 1 28351180
2006 PLAC1 mRNA in maternal blood correlates with Doppler waveform in uterine arteries in normal pregnancies at the second and third trimester. Annals of the New York Academy of Sciences 1 17108202
2026 Serum PLAC1 levels for differential diagnosis between cervical intraepithelial neoplasia and invasive cervical cancer: a prospective observational study. Cytotechnology 0 41884401
2026 Fundamental and unique roles of PLAC1 in the regulation of rat and human trophoblast cell development. Development (Cambridge, England) 0 42007670
2026 Plac1 Ablation Disrupts Signaling Pathways Essential for Prenatal Development and Induces a Preeclampsia-associated Transcriptomic Signature. bioRxiv : the preprint server for biology 0 42244670
2024 Changes in plasma PLAC-1 concentration and its expression during early-mid pregnancy in bovine placental tissues - a pilot study. BMC veterinary research 0 38378537

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