Affinage

SERPINB5

Serpin B5 · UniProt P36952

Length
375 aa
Mass
42.1 kDa
Annotated
2026-06-10
100 papers in source corpus 30 papers cited in narrative 30 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

SERPINB5 (maspin) is an epithelial non-inhibitory serpin that modulates cell adhesion, migration, invasion, angiogenesis, and apoptosis in a context-dependent manner, predominantly as an intracellular nucleocytoplasmic protein (PMID:20123984, PMID:10655109). In non-transformed epithelial cells maspin is an obligate soluble cytoplasmic and nuclear monomer that is neither glycosylated, cytoskeleton-associated, nor secreted via the classical pathway (PMID:20123984), and EGFR ligands drive its phosphorylation and EGF-stimulated nuclear accumulation (PMID:27447178). Extracellularly, maspin binds pro-uPA directly via its reactive-site-loop residue Arg340, inhibiting plasmin-mediated pro-uPA cleavage and promoting uPA/uPAR internalization to restrain pericellular proteolysis and cell detachment (PMID:16618739), and it physically associates with β1 integrin to regulate adhesion through a function localized to its G α-helix, which is sufficient to reproduce the anti-migratory effect (PMID:16720730, PMID:20837467); downstream it suppresses Rac1/Cdc42 and modulates FAK/ILK and PI3K/ERK signaling (PMID:14508113, PMID:20713357). Maspin's anti-angiogenic activity is mechanistically separable from its anti-motility activity, as RSL mutants that lose anti-motility function retain inhibition of endothelial migration and tube formation (PMID:10655109). Intracellularly maspin functions in apoptosis and chromatin-linked regulation by inhibiting HDAC1, which acetylates Ku70 and releases Bax to trigger Bax-dependent death (PMID:22076034, PMID:15688005), and it can act as an adaptor in a TRIM21–SERPINB5–GMPS complex that drives GMPS ubiquitination and represses TP53 (PMID:32005234). Its transcription is activated by p53, TAp63, tamoxifen-bound ERα, and myocardin, and is silenced by promoter DNA methylation and HDAC1/8-mediated histone deacetylation (PMID:10692390, PMID:15466179, PMID:15145521, PMID:24607789, PMID:14670180, PMID:32391971). A conditional knockout establishes context-specific tumor suppression in lung, mammary, and prostatic epithelia (PMID:27923833), though a separate knockout study found no effect of maspin re-expression on prostate tumor growth, invasion, or survival, indicating its tumor-suppressor role is highly context-dependent (PMID:24445777).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 1996 Medium

    Established that maspin acts at the cell surface to restrain tumor cell motility and invasion, framing it as a candidate suppressor of carcinoma invasiveness.

    Evidence Recombinant protein, time-lapse microscopy, Boyden chamber invasion, and antibody-blocking in mammary carcinoma cells

    PMID:8876194

    Open questions at the time
    • No molecular surface receptor identified
    • Mechanism downstream of membrane binding unresolved
  2. 2000 High

    Separated maspin's anti-angiogenic activity from its anti-motility activity, showing two genetically dissociable functions.

    Evidence Endothelial migration/tube assays, corneal pocket assay, RSL mutagenesis, xenograft

    PMID:10655109

    Open questions at the time
    • Endothelial receptor/target for anti-angiogenic effect not defined
    • Structural basis of separability unmapped
  3. 2000 High

    Identified maspin as a direct p53 transcriptional target, linking its induction to the DNA-damage/tumor-suppressor program.

    Evidence Promoter-reporter, EMSA, adenoviral p53, isogenic p53 cell lines

    PMID:10692390

    Open questions at the time
    • Does not address protein-level function
    • Tissue specificity of p53 control unclear
  4. 2003 High

    Demonstrated that maspin transcription is epigenetically gated by DNA methylation and histone acetylation, explaining its silencing in cancers.

    Evidence Bisulfite sequencing, ChIP, 5-aza-dC/TSA reactivation, reporter assays in pancreatic cancer cells

    PMID:14670180

    Open questions at the time
    • Does not identify the writers/readers targeting the locus
    • Causal order of methylation vs deacetylation unresolved
  5. 2003 Medium

    Connected maspin to extracellular uPA-dependent proteolysis and to intracellular Rho-family/PI3K-ERK signaling controlling adhesion and motility.

    Evidence ECM/collagen degradation, bone xenograft (uPA); Rac1 pull-down, PI3K/ERK inhibitor epistasis (signaling)

    PMID:12788977 PMID:14508113

    Open questions at the time
    • Direct biochemical maspin-uPA interaction not yet shown at this stage
    • Link between surface binding and intracellular signaling unclear
  6. 2004 High

    Showed TAp63 activates maspin via the p53 site, explaining maspin loss when p63 is lost in invasive cells.

    Evidence p63 transfection, reporter, EMSA, ChIP, siRNA loss-of-function, invasion assays in lung cancer

    PMID:15466179

    Open questions at the time
    • Relative contribution of p53 vs p63 in vivo not resolved
    • Isoform-specific control beyond TAp63 not addressed
  7. 2006 High

    Provided the direct biochemical mechanism for extracellular maspin: RSL Arg340-dependent pro-uPA binding that blocks its activation and promotes uPA/uPAR internalization.

    Evidence K_d determination, plasmin cleavage assay, R340A mutagenesis, Co-IP, immunofluorescence

    PMID:16618739

    Open questions at the time
    • Reconciliation with non-secreted intracellular pool not addressed
    • Stoichiometry within the uPAR-LRP complex unclear
  8. 2006 Medium

    Identified β1 integrin as a maspin partner controlling adhesion and mapped a required region (aa 139-225).

    Evidence Co-IP, RNAi, deletion mapping, adhesion assays, fractionation

    PMID:16720730

    Open questions at the time
    • Direct vs indirect integrin binding not distinguished
    • Single lab, no reciprocal structural validation
  9. 2010 High

    Refined the localization model, showing maspin is an obligate intracellular nucleocytoplasmic monomer in non-transformed epithelium, challenging the secreted/cell-surface model.

    Evidence Immunofluorescence, pulse-chase glycosylation, surface biotinylation, fractionation, 3D acini, signal-peptide fusion

    PMID:20123984

    Open questions at the time
    • How intracellular maspin reaches extracellular targets unresolved
    • Reconciliation with surface-binding reports incomplete
  10. 2010 High

    Localized maspin's anti-migratory/adhesion activity to the G α-helix, sufficient as a synthetic peptide and dependent on β1 integrins, distinct from the RSL.

    Evidence G-helix and P1 mutagenesis, 15-mer peptide reconstitution, integrin-blocking antibodies, migration/adhesion assays; endothelial integrin/ILK/FAK signaling

    PMID:20713357 PMID:20837467

    Open questions at the time
    • Structural details of G-helix/integrin contact unknown
    • Integration of G-helix and RSL functions unresolved
  11. 2011 Medium

    Defined an intracellular maspin pro-apoptotic mechanism via HDAC1 inhibition, Ku70 acetylation, and Bax release.

    Evidence HDAC1 activity assay, Ku70/Bax Co-IP, acetylation Western, cell death assays

    PMID:22076034

    Open questions at the time
    • Direct maspin-HDAC1 binding stoichiometry not defined
    • Generality across cell types not tested
  12. 2011 Medium

    Identified maspin protein interactions with KHDRBS3 and FBXO32 linking it to an RNA-binding/ubiquitin-ligase axis in gastric cancer.

    Evidence Yeast two-hybrid, reciprocal Co-IP, RNA Co-IP, RNAi, RT-PCR

    PMID:21725612

    Open questions at the time
    • Functional consequence of FBXO32 mRNA change unclear
    • Single lab, mechanism downstream undefined
  13. 2014 Medium

    Expanded transcriptional control to ERα/tamoxifen and myocardin, mapping responsive promoter elements and domains.

    Evidence Promoter-reporter with element/domain mutagenesis, ERα/ERβ reconstitution, myocardin transfection, epigenetic drug synergy

    PMID:15145521 PMID:24607789

    Open questions at the time
    • In vivo relevance of these regulators untested
    • Combinatorial logic with p53/p63 unresolved
  14. 2014 High

    A conditional knockout challenged the tumor-suppressor model, finding maspin re-expression did not affect prostate tumor growth, invasion, or survival.

    Evidence Conditional KO mice, in vivo tumor/metastasis assays, in vitro migration/invasion/survival, bioinformatic expression analysis

    PMID:24445777

    Open questions at the time
    • Cannot exclude context-specific suppressor roles in other tissues
    • Mechanism for discrepancy with overexpression studies unresolved
  15. 2016 Medium

    Linked EGFR signaling to maspin phosphorylation and EGF-driven nuclear accumulation, indicating regulated subcellular partitioning.

    Evidence High-resolution IEF phosphoform detection, EGF/TGFα treatment, nuclear fractionation, ligand blocking

    PMID:27447178

    Open questions at the time
    • Functional consequence of specific phosphoforms unknown
    • Kinases responsible not identified
  16. 2016 Medium

    Genetically established tissue-specific tumor-suppressor phenotypes for maspin loss in lung, mammary, and prostatic epithelia.

    Evidence Exon-4-deletion knockout mouse, breeding to bypass lethality, histopathology

    PMID:27923833

    Open questions at the time
    • Molecular drivers of each tissue phenotype undefined
    • Reconciliation with the negative conditional KO study unresolved
  17. 2017 Medium

    Showed maspin is exported as functional exosome cargo capable of suppressing stromal fibroblast chemotaxis, offering a route for non-classical secretion.

    Evidence Exosome isolation, EM/AFM, knockdown, recipient NIH3T3 chemotaxis assay

    PMID:28009978

    Open questions at the time
    • Loading mechanism into exosomes unknown
    • Receptor on recipient cells unidentified
  18. 2020 Medium

    Recast maspin as a molecular adaptor in a TRIM21-SERPINB5-GMPS ubiquitination complex that represses TP53 and confers radioresistance.

    Evidence Mass spectrometry, Co-IP of trimeric complex, CRISPR KO/overexpression, localization imaging, xenograft

    PMID:32005234

    Open questions at the time
    • Direct binding interfaces not mapped
    • Tissue generality of this oncogenic role untested
  19. 2020 Medium

    Reinforced the β1-integrin/FAK axis as a node through which maspin suppresses EMT and angiogenesis, and confirmed HDAC1/8 (not just methylation) as repressors via p53/histone-acetylation at the promoter.

    Evidence CRISPRa/siRNA epistasis with ITGB1, functional tumor assays (gastric); HDAC inhibitor and HDAC1/8 knockdown with ChIP (prostate)

    PMID:32391971 PMID:32409959

    Open questions at the time
    • Whether intracellular or extracellular maspin pool drives these effects unclear
    • Single-lab studies
  20. 2024 Medium

    Demonstrated a pro-tumorigenic context where SERPINB5 drives invasion via TNF-α/NF-κB activation, underscoring its context-dependent duality.

    Evidence Lentiviral overexpression/knockdown, NF-κB inhibitor (QNZ) epistasis, invasion/tube formation assays in colorectal cancer

    PMID:38460302

    Open questions at the time
    • Mechanism by which SERPINB5 activates NF-κB undefined
    • Reconciliation with tumor-suppressor contexts unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How maspin's intracellular nucleocytoplasmic pool, exosomal export, and extracellular receptor engagement are mechanistically unified — and what determines its switch between tumor-suppressive and pro-tumorigenic outputs — remains unresolved.
  • No structural model integrating G-helix/RSL functions
  • Determinants of context-dependent direction of effect unknown
  • Mechanism of non-classical secretion vs obligate intracellular localization unreconciled

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 2 GO:0060090 molecular adaptor activity 2 GO:0098772 molecular function regulator activity 2 GO:0140096 catalytic activity, acting on a protein 2
Localization
GO:0005886 plasma membrane 3 GO:0005634 nucleus 2 GO:0005576 extracellular region 1 GO:0005829 cytosol 1 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-74160 Gene expression (Transcription) 5 R-HSA-162582 Signal Transduction 4 R-HSA-4839726 Chromatin organization 3 R-HSA-5357801 Programmed Cell Death 3 R-HSA-1474244 Extracellular matrix organization 2
Partners
FBXO32GMPSHDAC1ITGB1KHDRBS3PLAUTRIM21XRCC6
Complex memberships
TRIM21–SERPINB5–GMPS complex

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 Recombinant maspin binds specifically to the cell surface of mammary carcinoma cells (shown by immunostaining) and inhibits cell motility and invasion; pre-treatment with anti-maspin antibody blocks these effects, but antibody added after cell-surface binding cannot reverse them, indicating maspin activity is membrane-associated. Time-lapse video microscopy, modified Boyden chamber invasion assays, immunostaining of cell-surface-bound protein, antibody blocking experiments Proceedings of the National Academy of Sciences of the United States of America Medium 8876194
2000 Maspin inhibits angiogenesis: it directly blocks migration, mitogenesis, and tube formation of cultured endothelial cells toward bFGF and VEGF in vitro, and inhibits corneal neovascularization in vivo. Maspin mutants with reactive-site loop (RSL) mutations that lose anti-motility activity against fibroblasts/keratinocytes/cancer cells retain anti-angiogenic activity, indicating the two functions are mechanistically separable. In vitro endothelial cell migration, mitogenesis, and tube formation assays; rat cornea pocket assay; RSL mutagenesis; xenograft tumor model Nature medicine High 10655109
2000 Wild-type p53 directly binds to a p53 consensus element in the maspin promoter and transcriptionally activates maspin expression; DNA-damaging agents induce endogenous maspin in wild-type p53 cells but not mutant-p53 cells. Adenoviral p53 overexpression, promoter-reporter assays, EMSA/DNA binding, pharmacological DNA-damage induction in isogenic cell lines The Journal of biological chemistry High 10692390
2003 Maspin inhibits urokinase-type plasminogen activator (uPA)-dependent extracellular matrix degradation in prostate cancer cells; maspin-expressing DU145 transfectants showed reduced ECM and collagen degradation, decreased osteolysis, decreased tumor growth, and decreased angiogenesis in a human fetal bone xenograft model, consistent with maspin blocking the pericellular uPA proteolytic cascade. In vitro ECM/collagen degradation assays, intratibial injection xenograft model (human fetal bone in immunodeficient mice), histology/immunostaining Proceedings of the National Academy of Sciences of the United States of America Medium 12788977
2003 Maspin promoter is controlled by epigenetic mechanisms (DNA methylation and histone deacetylation); treatment of maspin-negative pancreatic cancer cells with 5-aza-2'-deoxycytidine (DNA methyltransferase inhibitor) and trichostatin A (HDAC inhibitor) re-activates maspin mRNA expression. Maspin-positive pancreatic carcinoma cells have demethylated promoters with hyperacetylated H3/H4 histones, while maspin-negative cells have methylated, hypoacetylated promoters. Bisulfite genomic sequencing, chromatin immunoprecipitation (ChIP), 5-aza-dC and TSA pharmacological treatment, luciferase reporter assays Neoplasia (New York, N.Y.) High 14670180
2004 p63 (specifically TAp63) transcriptionally activates maspin by binding to the p53-binding site on the maspin promoter; maspin expression in lung cancer cell lines is strictly dependent on p63 presence and loss of p63 explains loss of maspin in highly invasive cells. Transient p63 transfection, maspin promoter-luciferase reporter, EMSA, chromatin immunoprecipitation (ChIP), siRNA/shRNA loss-of-function, cell invasion assays Cancer research High 15466179
2003 Maspin regulates cell motility through the Rho GTPase pathway: exogenous recombinant maspin and stable maspin transfection in MDA-MB-231 cells decreased Rac1 activity within 4 h and reduced its effector PAK1 within 12 h. Maspin also increased PI3K and ERK1/2 activities (PI3K upstream of ERK), promoting cell adhesion via the PI3K/ERK pathway. Rac1 activity pull-down assay, Western blotting for PAK1/PI3K/ERK, PI3K inhibitor (LY294002) epistasis, cell adhesion and motility assays, phalloidin/focal adhesion staining Cancer biology & therapy Medium 14508113
2006 Maspin physically associates with β1 integrin at the cell membrane to regulate cell adhesion; maspin co-localizes with detergent-insoluble cortical cytoskeleton elements (adhesion plaque), and a domain of 86 amino acids (aa 139–225) is required for this adhesion effect. Maspin knockdown by RNAi reduces adhesion, and the effect is β1 integrin-dependent. Co-immunoprecipitation, RNAi knockdown, recombinant protein deletion/mutation analysis, adhesion assays, subcellular fractionation FASEB journal : official publication of the Federation of American Societies for Experimental Biology Medium 16720730
2006 Maspin binds directly to pro-uPA (K_d ≈ 270 nM), inhibits plasmin-mediated pro-uPA cleavage, and promotes internalization of the uPA/uPAR complex; this requires the maspin RSL P1' Arg340, since R340A mutation abolishes both pro-uPA binding and the maspin effects on pro-uPA cleavage and cell detachment. Maspin also enhances the uPAR–LRP interaction and sustains mature focal adhesion contacts. Biophysical binding assay (K_d determination), plasmin cleavage assay, site-directed mutagenesis of RSL, co-localization immunofluorescence, cell detachment/adhesion assays, Co-IP Cancer research High 16618739
2005 Intracellular maspin overexpression in endothelial cells induces apoptosis involving changes in Bcl-2 family gene expression and caspase activation; this effect is dependent on the RSL region of maspin and is blocked by Bcl-2 overexpression or caspase inhibitors. Tumor neovessels (but not mature normal vessels) are disrupted by intravascular adenoviral maspin delivery in mice. Adenoviral overexpression in vitro and in vivo, apoptosis assays, caspase inhibitor blockade, Bcl-2 overexpression rescue, maspin RSL deletion mutants Oncogene Medium 15688005
2010 In non-transformed human epithelial cells (MCF10A, RWPE-1), maspin has an obligate intracellular, nucleocytoplasmic distribution; it is neither glycosylated nor secreted, not present at the cell surface (cell-surface biotinylation negative), not associated with the cytoskeleton, and exists as a soluble monomer. Addition of a signal peptide directs maspin into the secretory pathway producing glycosylation but not secretion. Indirect immunofluorescence, immunoblotting, pulse-chase glycosylation analysis, cell-surface biotinylation, subcellular fractionation, 3D acini differentiation, signal-peptide fusion construct The Journal of biological chemistry High 20123984
2010 Maspin enhances endothelial cell (HUVEC) adhesion through integrin β1 activation, which redistributes vinculin and F-actin and increases integrin-linked kinase (ILK) activity and FAK phosphorylation. During bFGF-stimulated migration, maspin decreases active Rac1 and Cdc42, elevates FAK-Tyr397 phosphorylation, reduces focal adhesion disassembly, and retards EC migration. Integrin activation assays, ILK activity assay, phospho-FAK Western blotting, Rac1/Cdc42 pull-down, F-actin/vinculin immunostaining, HUVEC migration assay The Journal of biological chemistry Medium 20713357
2010 The G α-helix of maspin is essential and sufficient for inhibiting cell migration and regulating cell adhesion; a 15-mer G-helix peptide mimics maspin's anti-migratory effect, and G-helix mutations abolish it. These G-helix effects depend on β1 integrins. Mutations at the P1 reactive center loop position or an internal salt bridge do not attenuate cell migration inhibition. Site-directed mutagenesis of G-helix, salt bridge, and P1 positions; synthetic peptide; cell migration and adhesion assays; integrin-blocking antibodies The Journal of biological chemistry High 20837467
2010 PAR-1 (thrombin receptor) negatively regulates maspin transcription in metastatic melanoma by reducing binding of Ets-1 and c-Jun to the maspin promoter; PAR-1 silencing increases CBP/p300 expression and decreases p38 activity, leading to enhanced Ets-1/c-Jun binding and maspin re-expression, which reduces melanoma invasiveness. Gene expression profiling, promoter-luciferase reporter, ChIP for Ets-1/c-Jun, CBP/p300 and p38 Western blotting, siRNA silencing, invasion assays, xenograft tumor models Proceedings of the National Academy of Sciences of the United States of America High 21187389
2011 Maspin inhibits HDAC1 and thereby increases acetylation of Ku70, causing dissociation of Bax from Ku70 and triggering Bax-dependent apoptosis. Maspin was identified as a Ku70-interacting molecule. HDAC1 activity assay, Ku70 acetylation Western blotting, Co-immunoprecipitation of maspin-Ku70 and Bax-Ku70 interactions, cell death assays International journal of molecular medicine Medium 22076034
2011 SerpinB5/maspin physically interacts with KHDRBS3 and FBXO32 in gastric cancer cells (confirmed by co-immunoprecipitation and yeast two-hybrid); KHDRBS3 in turn interacts with FBXO32 mRNA (RNA Co-IP), and changes in SerpinB5 expression alter FBXO32 mRNA levels 24 h after KHDRBS3 protein levels change. Yeast two-hybrid screening, co-immunoprecipitation, RNA co-immunoprecipitation, RNAi knockdown, Western blotting, RT-PCR Oncology reports Medium 21725612
2007 Maspin expression is induced by proteasome inhibitors via a p38MAPK/AP-1 pathway; maspin siRNA attenuates proteasome inhibitor-induced apoptosis, and maspin-transfected prostate cancer cells show enhanced apoptosis with proteasome inhibitors. AP-1 activation by p38MAPK (not ERK1/2 or NF-κB) drives maspin transcription. EMSA, promoter-reporter assays, p38MAPK/ERK/NF-κB inhibitors for pathway epistasis, maspin siRNA knockdown, apoptosis assays Journal of cellular physiology Medium 17458898
2009 PTEN and p53 act in tandem to induce maspin expression under hypoxia: nuclear PTEN complexes with p53, while cytoplasmic PTEN prevents Mdm2 nuclear entry (by attenuating Akt), protecting p53 from degradation. Combined PTEN/p53 presence coordinates maspin and p21 induction. Altering PTEN or p53 expression attenuated maspin induction. Subcellular fractionation, Co-IP of PTEN-p53 complex, Akt inhibition, genetic knockdown of PTEN and p53, immunohistochemistry of xenograft tumors, Western blotting Cell cycle (Georgetown, Tex.) Medium 19221500
2008 Maspin enhances sensitivity of prostate cancer cells to hypoxia-induced apoptosis; maspin-overexpressing DU-145 cells show increased apoptosis and reduced tumor growth/vascularity under hypoxia, with suppression of Akt and focal adhesion kinase (FAK) activation as the mechanistic basis. Maspin stable transfection, hypoxia chamber (1% O2), apoptosis assays, phospho-Akt/FAK Western blotting, in vivo xenograft tumor growth and vascularity analysis Oncogene Medium 18931702
2012 Maspin downregulation (by shRNA or E2F1-DP1 overexpression) dramatically accelerates cell cycle progression in gastric cancer cells with increased active CDC25C and decreased inactive CDK1, while maspin upregulation retards cell proliferation, establishing maspin as a cell cycle regulator. shRNA knockdown, E2F1-DP1 overexpression, flow cytometry cell cycle analysis, Western blotting for CDC25C and CDK1 phosphorylation states Carcinogenesis Medium 22962304
2014 Myocardin activates maspin transcription through a CArG box in the maspin promoter; this is demonstrated by luciferase reporter assay. Combined treatment with 5-aza-dC/TSA (epigenetic de-repression) and myocardin synergistically enhances maspin re-expression and maspin-mediated apoptosis in MCF-7 breast cancer cells. Luciferase reporter assay with CArG box mutagenesis, myocardin transfection, 5-aza-dC/TSA epigenetic drug treatment, apoptosis assays Cellular signalling Medium 24607789
2016 EGFR ligands (EGF, TGFα) regulate maspin/SerpinB5 phosphorylation in mammary epithelial cells; EGF specifically induces SerpinB5 nuclear accumulation. At least 8 different SerpinB5 phosphoforms were detected by high-resolution isoelectric focusing during lactation. Amphiregulin autocrine activity maintains basal phosphorylation. High-resolution isoelectric focusing/immunoblot for phosphoform detection, EGF/TGFα treatment, nuclear fractionation/imaging for localization, EGFR ligand blocking experiments PloS one Medium 27447178
2020 SERPINB5/maspin acts as an adaptor protein in the TRIM21-SERPINB5-GMPS complex: SERPINB5 prevents GMPS from entering the nucleus and recruits TRIM21 (an E3 ubiquitin ligase) to ubiquitinate and degrade GMPS, thereby repressing TP53 expression and promoting radioresistance in nasopharyngeal carcinoma cells. Mass spectrometry identification of TRIM21 targets, Co-immunoprecipitation of TRIM21-SERPINB5-GMPS complex, CRISPR knockout and overexpression, flow cytometry, immunofluorescence for subcellular localization, in vivo xenograft Journal of biomedical science Medium 32005234
2020 Maspin inhibits EMT and angiogenesis in gastric cancer by blocking the ITGB1/FAK signaling pathway; maspin overexpression decreases ITGB1 and p-FAK, reduces Vimentin and VEGF while increasing E-cadherin, and maspin knockdown restores these phenotypes even when ITGB1 is silenced. CRISPR activation, siRNA knockdown, Western blotting, tube formation assay, Transwell invasion/migration, wound healing assay, IHC of patient tissues Human cell Medium 32409959
2020 Class I HDACs (specifically HDAC1 and HDAC8) repress maspin in prostate cancer cells independent of promoter DNA hypermethylation; HDAC inhibitors (sodium butyrate, TSA) re-express maspin, and this is accompanied by p53 enrichment at the maspin promoter with increased H3/H4 acetylation, suppressing prostate cancer cell proliferation and migration. HDAC inhibitor treatment (sodium butyrate, TSA), ChIP for p53 and acetyl-H3/H4 at maspin promoter, HDAC1/HDAC8 siRNA knockdown, methylation analysis, proliferation and migration assays Molecular carcinogenesis Medium 32391971
2014 Tamoxifen induces maspin expression through estrogen receptor alpha (ERα) but not ERβ; this requires the ERα LBD-AF2 domain (LBDmtL539A mutation abolishes activation) and cis-elements between -90 and +87 bp of the maspin promoter (not the HRE at -272 bp). The ERα N-terminal AF-1 domain is critical for basal maspin transcription activation. Maspin-luciferase reporter assay, ERα/ERβ reconstitution in cell culture, ERα deletion/point mutants, promoter deletion analysis Cancer letters Medium 15145521
2017 Maspin is secreted as an exosome cargo protein: electron microscopy shows maspin encapsulated within the exosomal membrane. Maspin-devoid exosomes (from maspin-knockdown MCF-10A cells) have significantly reduced suppressive effects on chemotaxis of recipient NIH3T3 fibroblasts, demonstrating that exosomal maspin can suppress tumor-induced stromal responses. Exosome isolation/fractionation, electron microscopy, atomic force microscopy, dynamic light scattering, Western blotting of exosome fractions, maspin siRNA knockdown, NIH3T3 fibroblast chemotaxis assay Oncotarget Medium 28009978
2014 Maspin re-expression in prostate tumor cells does NOT inhibit tumor growth or metastasis in vivo and does not influence cell migration, invasion, or survival in vitro in a conditional knockout study; maspin knockout mice develop into overtly normal adults, contrary to original reports of embryonic lethality. Bioinformatic analyses show maspin is not commonly under-expressed in cancer. Conditional knockout mouse generation, tumor growth/metastasis assays in vivo, cell migration/invasion/survival assays in vitro, bioinformatic expression analysis Nature communications High 24445777
2016 Maspin deficiency in mice (exon 4 deletion) causes pulmonary adenocarcinoma, mammary myoepithelial hyperplasia, prostatic luminal hyperplasia, and alopecia areata, establishing context-specific tumor suppressor roles for maspin in vivo. Conditional knockout mouse generation (exon 4 deletion), breeding scheme to bypass embryonic lethality, histopathological phenotyping Cancer research Medium 27923833
2024 SERPINB5 promotes invasion and migration of colorectal cancer cells by activating the TNF-α/NF-κB pathway (increasing p-NF-κB/p65, N-cadherin, MMP2, MMP9, VEGFA and decreasing E-cadherin); these effects were reversed by QNZ (NF-κB inhibitor), placing SERPINB5 upstream of NF-κB in this pro-tumorigenic context. Lentiviral overexpression/knockdown, Western blotting, Transwell invasion/migration, proliferation assays, HUVEC tube formation assay, NF-κB pathway inhibitor (QNZ) epistasis International immunopharmacology Medium 38460302

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 Maspin is an angiogenesis inhibitor. Nature medicine 386 10655109
1996 Maspin acts at the cell membrane to inhibit invasion and motility of mammary and prostatic cancer cells. Proceedings of the National Academy of Sciences of the United States of America 327 8876194
2000 p53 regulates the expression of the tumor suppressor gene maspin. The Journal of biological chemistry 237 10692390
2001 Expression of the tumor suppressor gene Maspin in human pancreatic cancers. Clinical cancer research : an official journal of the American Association for Cancer Research 143 11309327
2003 Maspin expression inhibits osteolysis, tumor growth, and angiogenesis in a model of prostate cancer bone metastasis. Proceedings of the National Academy of Sciences of the United States of America 128 12788977
2006 Biological functions of maspin. Journal of cellular physiology 125 17001697
2006 Maspin: the new frontier. Clinical cancer research : an official journal of the American Association for Cancer Research 104 17189399
2001 Expression of the p53 and Maspin protein in primary prostate cancer: correlation with clinical features. International journal of cancer 104 11494236
2013 Role of maspin in cancer. Clinical and translational medicine 92 23497644
2012 Maspin: molecular mechanisms and therapeutic implications. Cancer metastasis reviews 83 22752408
2006 Tumor suppressive maspin and epithelial homeostasis. Journal of cellular biochemistry 75 16329135
2006 Maspin retards cell detachment via a novel interaction with the urokinase-type plasminogen activator/urokinase-type plasminogen activator receptor system. Cancer research 66 16618739
2003 Maspin regulates different signaling pathways for motility and adhesion in aggressive breast cancer cells. Cancer biology & therapy 63 14508113
1996 Maspin: a tumor suppressing serpin. Current topics in microbiology and immunology 63 8814994
2001 Maspin expression in stage I and II oral tongue squamous cell carcinoma. Head & neck 56 11754500
2000 Maspin--a novel protease inhibitor with tumor-suppressing activity in breast cancer. Acta oncologica (Stockholm, Sweden) 55 11206999
2006 Maspin is physically associated with [beta]1 integrin regulating cell adhesion in mammary epithelial cells. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 52 16720730
2003 Genetic and physical mapping of Pi5(t), a locus associated with broad-spectrum resistance to rice blast. Molecular genetics and genomics : MGG 50 12756540
2004 Maspin expression is transactivated by p63 and is critical for the modulation of lung cancer progression. Cancer research 49 15466179
2005 Targeted expression of maspin in tumor vasculatures induces endothelial cell apoptosis. Oncogene 48 15688005
2003 Clinicopathological significance and molecular regulation of maspin expression in ductal adenocarcinoma of the pancreas. Cancer letters 48 12969792
2001 Maspin expression in myoepithelial tumors of the breast. Pathology, research and practice 48 11795829
2020 TRIM21-SERPINB5 aids GMPS repression to protect nasopharyngeal carcinoma cells from radiation-induced apoptosis. Journal of biomedical science 43 32005234
1997 Gamma linolenic acid regulates expression of maspin and the motility of cancer cells. Biochemical and biophysical research communications 43 9299418
2010 Maspin regulates endothelial cell adhesion and migration through an integrin signaling pathway. The Journal of biological chemistry 42 20713357
2003 Modeling human breast cancer metastasis in mice: maspin as a paradigm. Histology and histopathology 42 12507299
2003 Human pancreatic carcinoma cells activate maspin expression through loss of epigenetic control. Neoplasia (New York, N.Y.) 42 14670180
2010 Maspin (SERPINB5) is an obligate intracellular serpin. The Journal of biological chemistry 41 20123984
2010 Protease activated receptor-1 inhibits the Maspin tumor-suppressor gene to determine the melanoma metastatic phenotype. Proceedings of the National Academy of Sciences of the United States of America 38 21187389
2015 Expression and clinical significance of microRNA-21, maspin and vascular endothelial growth factor-C in bladder cancer. Oncology letters 37 26622898
2004 Maspin expression and its clinicopathological significance in tumorigenesis and progression of gastric cancer. World journal of gastroenterology 37 14991928
2002 Maspin expression in normal skin and usual cutaneous carcinomas. Virchows Archiv : an international journal of pathology 36 12461611
2004 Expression and regulation of tumor suppressor gene maspin in human bladder cancer. Cancer letters 35 14732229
2010 MALDI-TOF mass array analysis of RASSF1A and SERPINB5 methylation patterns in human placenta and plasma. Biology of reproduction 33 20075396
2007 Maspin augments proteasome inhibitor-induced apoptosis in prostate cancer cells. Journal of cellular physiology 33 17458898
2016 TMEM45A, SERPINB5 and p16INK4A transcript levels are predictive for development of high-grade cervical lesions. American journal of cancer research 32 27508094
2012 Expression of maspin in non-small cell lung cancer and its relationship to vasculogenic mimicry. Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban 32 22684556
2011 Expression of Ets-1, Ang-2 and maspin in ovarian cancer and their role in tumor angiogenesis. Journal of experimental & clinical cancer research : CR 32 21439064
2006 A role of novel serpin maspin in tumor progression: the divergence revealed through efforts to converge. Journal of cellular physiology 32 17001674
2006 Maspin expression and its clinical significance in non-small cell lung cancer. Annals of surgical oncology 32 17009165
2020 Maspin suppresses cell invasion and migration in gastric cancer through inhibiting EMT and angiogenesis via ITGB1/FAK pathway. Human cell 31 32409959
2010 The natural tumor suppressor protein maspin and potential application in non small cell lung cancer. Current pharmaceutical design 31 20337574
2010 G-helix of maspin mediates effects on cell migration and adhesion. The Journal of biological chemistry 31 20837467
2009 PTEN and p53 are required for hypoxia induced expression of maspin in glioblastoma cells. Cell cycle (Georgetown, Tex.) 31 19221500
2007 Maspin expression was involved in colorectal adenoma-adenocarcinoma sequence and liver metastasis of tumors. Anticancer research 31 17352241
2005 Epigenetic status and aberrant expression of the maspin gene in human hepato-biliary tract carcinomas. Laboratory investigation; a journal of technical methods and pathology 30 15608662
2024 SERPINB5 promotes colorectal cancer invasion and migration by promoting EMT and angiogenesis via the TNF-α/NF-κB pathway. International immunopharmacology 29 38460302
2007 Paradoxical expression of maspin in gastric carcinomas: correlation with carcinogenesis and progression. Human pathology 29 17490717
2006 Maspin and tumor metastasis. IUBMB life 29 16540429
2016 Serpin peptidase inhibitor (SERPINB5) haplotypes are associated with susceptibility to hepatocellular carcinoma. Scientific reports 27 27221742
2008 Maspin modulates prostate cancer cell apoptotic and angiogenic response to hypoxia via targeting AKT. Oncogene 27 18931702
2002 Expression and regulation of tumor suppressor gene maspin in breast cancer. Clinical breast cancer 27 12425757
2010 Aberrant maspin expression is involved in early carcinogenesis of gallbladder cancer. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 26 20517662
2008 Expression of maspin in non-small-cell lung cancer: correlation with clinical features. Clinical lung cancer 26 19073519
2006 Expression of maspin in colorectal cancer. In vivo (Athens, Greece) 26 17203770
2003 Silencing of the maspin gene by promoter hypermethylation in thyroid cancer. International journal of molecular medicine 26 12964023
2021 Subcellular Expression of Maspin in Colorectal Cancer: Friend or Foe. Cancers 25 33498377
2017 Nuclear maspin expression: A biomarker for budding assessment in colorectal cancer specimens. Pathology, research and practice 25 28780084
2014 Maspin is not required for embryonic development or tumour suppression. Nature communications 25 24445777
2010 SERPINB5 and AKAP12 - expression and promoter methylation of metastasis suppressor genes in pancreatic ductal adenocarcinoma. BMC cancer 25 20939879
2014 Re-expression and epigenetic modification of maspin induced apoptosis in MCF-7 cells mediated by myocardin. Cellular signalling 24 24607789
2008 Epigenetic silencing of maspin expression occurs early in the conversion of keratocytes to fibroblasts. Experimental eye research 24 18291368
2017 Sulforaphane-cysteine-induced apoptosis via phosphorylated ERK1/2-mediated maspin pathway in human non-small cell lung cancer cells. Cell death discovery 23 28690874
2004 Tamoxifen induces the expression of maspin through estrogen receptor-alpha. Cancer letters 23 15145521
2020 Role of class I histone deacetylases in the regulation of maspin expression in prostate cancer. Molecular carcinogenesis 22 32391971
2016 IKKα inibition by a glucosamine derivative enhances Maspin expression in osteosarcoma cell line. Chemico-biological interactions 21 27931795
2011 SerpinB5 interacts with KHDRBS3 and FBXO32 in gastric cancer cells. Oncology reports 21 21725612
2008 MASPIN subcellular localization and expression in oral cavity squamous cell carcinoma. European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery 21 18236066
2004 Maspin expression in normal and neoplastic salivary gland. Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology 21 15250837
2016 An Essential Role of Maspin in Embryogenesis and Tumor Suppression. Cancer research 20 27923833
2012 Maspin genetically and functionally associates with gastric cancer by regulating cell cycle progression. Carcinogenesis 20 22962304
2011 Maspin expression is frequent and correlates with basal markers in triple-negative breast cancer. Diagnostic pathology 20 21496280
2017 The secretion and biological function of tumor suppressor maspin as an exosome cargo protein. Oncotarget 19 28009978
2015 Maspin Expression in Prostate Tumor Cells Averts Stemness and Stratifies Drug Sensitivity. Cancer research 19 26208903
2009 MASPIN tumour-suppressing activity in head and neck squamous cell carcinoma: emerging evidence and therapeutic perspectives. Acta oto-laryngologica 19 18615330
2004 Use of Pi5(t) markers in marker-assisted selection to screen for cultivars with resistance to Magnaporthe grisea. TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik 19 15141293
2002 Expression of maspin in pancreatic neoplasms: application of maspin immunohistochemistry to the differential diagnosis. Applied immunohistochemistry & molecular morphology : AIMM 19 11893038
2013 Possible predictive value of maspin expression in colorectal cancer. Recent patents on anti-cancer drug discovery 18 22963136
2005 Maspin expression in carcinoma ex pleomorphic adenoma. Journal of clinical pathology 18 16311353
2014 Maspin expression in prostate tumor elicits host anti-tumor immunity. Oncotarget 17 25373490
2012 Predictive value of maspin and Ki-67 expression in transurethral resection specimens in patients with T1 bladder cancer. Tumori 17 22825520
2011 Maspin increases Ku70 acetylation and Bax-mediated cell death in cancer cells. International journal of molecular medicine 17 22076034
2019 Pi5 and Pii Paired NLRs Are Functionally Exchangeable and Confer Similar Disease Resistance Specificity. Molecules and cells 16 31564075
2016 Maspin-related Orchestration of Aggressiveness of Gastric Cancer. Applied immunohistochemistry & molecular morphology : AIMM 16 26067133
2024 miR-1204 Positioning in 8q24.21 Involved in the Tumorigenesis of Colorectal Cancer by Targeting MASPIN. Protein and peptide letters 15 39082173
2020 Maspin expression and anti-apoptotic pathway regulation by bcl2 in laryngeal cancer. Annals of diagnostic pathology 15 31986422
2007 Maspin expression in oral squamous cell carcinoma. The Journal of craniofacial surgery 15 17912078
2006 Simultaneous evaluation of maspin and CXCR4 in patients with breast cancer. Journal of clinical pathology 15 16751302
2005 Maspin and c-erbB-2 expression in correlation with microvessel density in invasive ductal breast cancer. Folia histochemica et cytobiologica 15 16044948
2020 The roles of MASPIN expression and subcellular localization in non-small cell lung cancer. Bioscience reports 14 32391558
2013 Maspin expression and melanoma progression: a matter of sub-cellular localization. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 14 24030740
2008 Cytoplasmic and nuclear maspin expression in lung carcinomas: an immunohistochemical study using tissue microarrays. Applied immunohistochemistry & molecular morphology : AIMM 14 18665036
2006 Nuclear maspin detection in renal cell tumours: possible diagnostic role and correlation with p53 status. Histopathology 14 16918974
2004 Multiple functions of maspin in tumor progression and mouse development. Frontiers in bioscience : a journal and virtual library 14 15353283
2014 Promoter hypomethylation and increased maspin expression in preeclamptic placentas in a Chinese population. Placenta 13 25151033
2005 Expression of maspin in mammary gland tumors of the dog. Veterinary pathology 13 15872371
2005 Expression of maspin in gestational trophoblastic disease. Gynecologic oncology 13 16271752
2020 Maspin subcellular expression in wild-type and mutant TP53 gastric cancers. World journal of gastrointestinal oncology 12 32864042
2016 SERPINB5 Promoter Hypomethylation Differentiates Pancreatic Ductal Adenocarcinoma From Pancreatitis. Pancreas 12 26646275
2016 EGFR Signaling Regulates Maspin/SerpinB5 Phosphorylation and Nuclear Localization in Mammary Epithelial Cells. PloS one 12 27447178

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