Affinage

SERPINB5

Serpin B5 · UniProt P36952

Length
375 aa
Mass
42.1 kDa
Annotated
2026-04-28
100 papers in source corpus 30 papers cited in narrative 30 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SERPINB5 (maspin) is a non-inhibitory serpin that functions as a tumor suppressor by integrating extracellular protease regulation, intracellular signaling modulation, and pro-apoptotic activity across epithelial and endothelial contexts. Extracellularly, maspin binds pro-uPA via its reactive site loop (RSL) and a distinct exosite (Kd ~270–600 nM), inhibiting plasmin-mediated uPA activation, stabilizing focal adhesions, and suppressing ECM degradation, while its G α-helix mediates β1-integrin-dependent inhibition of cell migration (PMID:16618739, PMID:17510061, PMID:20837467). Intracellularly, maspin suppresses Rac1/Cdc42 GTPase activity through the RSL to inhibit motility, directly inhibits HDAC1 to promote Ku70 acetylation and Bax-dependent apoptosis, modulates Bcl-2/Bax balance and AKT/FAK signaling, and induces endothelial cell apoptosis to block tumor angiogenesis (PMID:17301947, PMID:22076034, PMID:15907209, PMID:15688005). Transcription of SERPINB5 is activated by p53 and TAp63 binding its promoter and is epigenetically silenced through CpG methylation and histone deacetylation in multiple cancer types, with additional repression by nuclear IKKα (RANKL-dependent), Snail, and PAR-1 signaling (PMID:10692390, PMID:15466179, PMID:17377533, PMID:14670180, PMID:22857708, PMID:21187389).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2000 High

    Establishing the transcriptional control of maspin by p53 answered how a known tumor suppressor directly regulates maspin expression, linking maspin to the DNA-damage response network.

    Evidence Promoter reporter assays, EMSA, and RT-PCR in prostate and breast cancer cells with wild-type vs. mutant p53

    PMID:10692390

    Open questions at the time
    • No in vivo confirmation of p53-dependent maspin induction
    • Chromatin context of p53 binding not addressed
  2. 2002 High

    Demonstrating that maspin silencing in breast cancer results from CpG promoter methylation and histone deacetylation explained why maspin is lost in tumors despite an intact gene, establishing epigenetic regulation as the primary silencing mechanism.

    Evidence 5-aza-dC and TSA treatment restoring maspin expression in maspin-negative breast cancer lines, with promoter reporter assays

    PMID:12220518 PMID:14670180

    Open questions at the time
    • Methyltransferase(s) responsible not identified
    • Mechanism linking methylation to histone deacetylation at the maspin locus not resolved
  3. 2003 High

    Showing that maspin suppresses ECM degradation, angiogenesis, and osteolysis in vivo and inhibits Rac1 signaling established both extracellular and intracellular effector mechanisms for maspin's tumor-suppressive activity.

    Evidence In vitro ECM degradation assays, DU145 xenograft in human bone implants, Rac1 pull-down and PI3K inhibitor studies in MDA-MB-231 cells

    PMID:12788977 PMID:14508113

    Open questions at the time
    • Direct molecular target mediating Rac1 inhibition not identified
    • Whether extracellular and intracellular functions are separable in vivo remained unclear
  4. 2004 High

    Identifying TAp63 as a maspin transcriptional activator and tamoxifen-bound ERα as an inducer expanded the network of upstream regulators beyond p53, connecting maspin to differentiation and hormonal signaling.

    Evidence ChIP and EMSA for p63 binding at the p53 site; ERα domain-deletion promoter reporter analysis

    PMID:15145521 PMID:15466179

    Open questions at the time
    • In vivo relevance of ERα-mediated maspin induction not tested
    • Relative contribution of p53 vs. p63 in different tissues undefined
  5. 2005 High

    Demonstrating that maspin shifts Bcl-2/Bax balance and induces endothelial apoptosis via its RSL established maspin as a direct pro-apoptotic effector with anti-angiogenic consequences.

    Evidence Maspin overexpression in mammary tumor cells and adenoviral delivery to endothelial cells in tumor-bearing mice, with caspase inhibitor and Bcl-2 rescue

    PMID:15688005 PMID:15907209

    Open questions at the time
    • Direct protein target mediating Bcl-2 downregulation not identified
    • Whether RSL-dependent apoptosis requires protease interaction or a distinct target unknown
  6. 2006 High

    Biochemical demonstration that maspin binds pro-uPA through its RSL (Arg340-dependent, Kd ~270 nM) and subsequently through an exosite resolved how maspin inhibits plasminogen activation without classical serpin mechanism.

    Evidence Fluorescence binding assays, R340A mutagenesis, co-localization with uPA/uPAR/LRP, tPA binding to S195A mutant

    PMID:16618739 PMID:17510061

    Open questions at the time
    • Crystal structure of maspin–uPA complex lacking
    • Contribution of exosite vs. RSL binding to in vivo anti-metastatic activity not dissected
  7. 2007 High

    Identifying nuclear IKKα as a RANKL-induced repressor of maspin in vivo — with genetic epistasis showing maspin loss restores metastasis — provided a direct causal link between NF-κB pathway activation and maspin-dependent metastasis suppression.

    Evidence IKKα knock-in mutation in TRAMP prostate cancer model; maspin ablation rescue of metastasis

    PMID:17377533

    Open questions at the time
    • Mechanism by which nuclear IKKα represses maspin promoter not fully elucidated
    • Whether IKKα directly modifies maspin chromatin or acts through intermediary transcription factors unclear
  8. 2007 High

    Demonstrating RSL-dependent inhibition of Rac1 and Cdc42 (but not RhoA) with downstream JNK/AP-1 suppression clarified the intracellular signaling mechanism by which maspin controls cell migration.

    Evidence GTPase pull-down, RSL deletion/point mutants, immuno-kinase and AP-1 reporter assays in mammary tumor cells

    PMID:17301947

    Open questions at the time
    • Whether maspin directly binds Rac1/Cdc42 or acts through a GAP/GEF not resolved
    • Structural basis for RSL-mediated GTPase inhibition unknown
  9. 2010 High

    Mapping the G α-helix as necessary and sufficient for migration inhibition through β1-integrin dependence identified a second functional surface on maspin distinct from the RSL, resolving how maspin engages the adhesion machinery.

    Evidence G-helix point mutants, 15-mer peptide reconstitution, β1-integrin blocking antibody in migration and adhesion assays

    PMID:20837467

    Open questions at the time
    • Direct binding partner on integrin or integrin-associated complex not identified
    • Relationship between G-helix and RSL functions in vivo not addressed
  10. 2011 Medium

    Showing that maspin directly inhibits HDAC1 to increase Ku70 acetylation and liberate Bax for mitochondrial apoptosis provided a mechanistic basis for maspin's intracellular pro-apoptotic function and connected it to epigenetic regulation.

    Evidence Co-IP of maspin with Ku70, HDAC1 activity assay, Ku70 acetylation and Bax dissociation measurements

    PMID:22076034

    Open questions at the time
    • Direct maspin–HDAC1 binding interface not mapped
    • Whether maspin inhibits other HDACs not tested
    • Single-lab finding without independent replication
  11. 2012 Medium

    Identifying Snail as a direct transcriptional repressor and showing maspin regulates CDC25C/CDK1-dependent cell cycle progression expanded maspin's functional repertoire beyond migration and apoptosis to include proliferation control and EMT transcription factor crosstalk.

    Evidence ChIP for Snail at maspin promoter; maspin shRNA/overexpression with CDC25C/CDK1 phosphorylation readouts in gastric cancer cells

    PMID:22857708 PMID:22962304

    Open questions at the time
    • Whether cell-cycle regulation is a primary or secondary effect of maspin unclear
    • Direct molecular link between maspin and CDC25C/CDK1 not established
  12. 2017 Medium

    Discovery that maspin is secreted within exosomes and that exosomal maspin suppresses fibroblast chemotaxis revealed a paracrine tumor-suppressive mechanism extending maspin's action to the tumor microenvironment.

    Evidence Exosome isolation with EM/AFM, maspin knockdown producing maspin-devoid exosomes, NIH3T3 chemotaxis assay

    PMID:28009978

    Open questions at the time
    • Exosomal maspin cargo sorting mechanism unknown
    • In vivo relevance of exosomal maspin not tested
    • Single-lab finding
  13. 2021 Medium

    Demonstrating that cytoplasmic maspin in aggressive breast cancer promotes EMT via SRGN/TGFβ activation while nuclear maspin is tumor-suppressive revealed context-dependent, subcellular-localization-determined duality in maspin function.

    Evidence Stable maspin overexpression/knockdown in MDA-MB-231 with EMT marker and TGFβ pathway analysis

    PMID:34059749

    Open questions at the time
    • Mechanism controlling nuclear vs. cytoplasmic partitioning not identified
    • How cytoplasmic maspin activates SRGN/TGFβ not defined
    • Single-lab observation in one cell line
  14. 2024 Medium

    Showing that SERPINB5 overexpression in colorectal cancer activates TNF-α/NF-κB signaling to promote EMT and angiogenesis reinforced the emerging model that maspin can have oncogenic functions in specific cellular contexts.

    Evidence Lentiviral overexpression/knockdown in CRC cells, NF-κB inhibitor (QNZ) rescue, HUVEC tube formation assay

    PMID:38460302

    Open questions at the time
    • Mechanism linking maspin to TNF-α/NF-κB activation not identified
    • Apparent contradiction with classic tumor-suppressive role not reconciled at molecular level
    • Single-lab study

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: how subcellular localization determines tumor-suppressive vs. oncogenic function; whether maspin directly binds Rac1/Cdc42 or HDAC1 and through which structural surfaces; and the structural basis for non-inhibitory serpin activity in vivo.
  • No crystal structure of maspin in complex with any of its functional partners
  • Nuclear vs. cytoplasmic sorting mechanism unknown
  • No unified model reconciling tumor-suppressive and tumor-promoting activities across tissue types

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 4 GO:0140096 catalytic activity, acting on a protein 1
Localization
GO:0005576 extracellular region 4 GO:0005829 cytosol 4 GO:0005634 nucleus 2 GO:0031410 cytoplasmic vesicle 2
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-1500931 Cell-Cell communication 2
Partners
FBXO32HDAC1ITGB1KHDRBS3PLATPLAU

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 Wild-type p53 directly activates maspin transcription by binding to a p53 consensus-binding site in the maspin promoter, as demonstrated by promoter reporter assays and gel-shift experiments; DNA-damaging agents induced maspin expression in cells with wild-type p53 but not mutant p53. Adenoviral p53 overexpression, promoter reporter assay, gel-shift (EMSA), RT-PCR in prostate and breast cancer cell lines The Journal of biological chemistry High 10692390
2004 p63 (specifically TAp63) is a critical transcriptional activator of maspin in lung cancer cells, binding to the previously identified p53-binding site on the maspin promoter, as shown by gel-shift and chromatin immunoprecipitation assays. Transient transfection, promoter reporter assay, EMSA, ChIP Cancer research High 15466179
2007 Nuclear IKKα activated by RANKL represses maspin transcription in prostate epithelial cells; a mutation preventing IKKα activation led to elevated maspin expression and reduced metastasis in TRAMP mice, with ablation of maspin restoring metastatic activity. Genetic mouse model (TRAMP), IKKα knock-in mutation, nuclear IKKα translocation assay, epistasis rescue experiment Nature High 17377533
2006 Maspin binds to pro-uPA (K_d ~270 nM) via its reactive site loop (RSL), with Arg340 (P1' site) critical for binding; this interaction inhibits plasmin-mediated pro-uPA cleavage and promotes internalization of uPA/uPAR, thereby stabilizing focal adhesion contacts and retarding cell detachment. Biochemical binding assay (fluorescence), site-directed mutagenesis (R340A), co-localization, cell detachment assay, LRP co-IP Cancer research High 16618739
2007 Maspin binds uPA and tPA through an exosite on maspin near but outside its reactive center loop, with K_d values 300–600 nM; the binding site on tPA does not involve the proteinase active site, and RCL mutation (Arg340) does not abolish binding, indicating exosite–exosite interactions. Fluorescence binding assays (intrinsic and extrinsic), RCL mutagenesis, binding to S195A tPA already complexed with PAI-1 The Journal of biological chemistry High 17510061
2010 The G α-helix of maspin is essential and sufficient for inhibiting cell migration and mediating effects on cell adhesion; these effects are dependent on β1 integrins, as demonstrated by point mutations and a 15-mer G-helix peptide mimicking full-length maspin activity. Site-directed mutagenesis, peptide reconstitution, cell migration assay, cell adhesion assay, β1-integrin blocking The Journal of biological chemistry High 20837467
2007 Maspin inhibits Rac1 and Cdc42 GTPase activity (but not RhoA) to control mammary tumor cell migration; the reactive site loop (RSL) of maspin is required for this inhibition, and downstream JNK kinase activity and AP-1 transcription are suppressed. GST-PAK and GST-Rho binding pull-down for GTP-bound GTPases, RSL deletion/point-mutation analysis, immuno-kinase assay, AP-1 reporter assay Cell motility and the cytoskeleton High 17301947
2003 Maspin inhibits uPA-mediated extracellular matrix degradation and collagen remodeling in vitro, and maspin-expressing DU145 prostate cancer cells injected into human fetal bone implants show decreased tumor growth, reduced osteolysis, decreased angiogenesis, increased fibrosis, and glandular redifferentiation in vivo. In vitro ECM/collagen degradation assays, maspin-transfectant xenograft model in immunodeficient mice with human fetal bone Proceedings of the National Academy of Sciences of the United States of America High 12788977
2005 Maspin overexpression reduces Bcl-2 protein levels and increases Bax protein levels post-translationally, leading to increased cytochrome c release and apoptosis in mammary tumor cells under staurosporine and serum starvation; the effect is intracellular and is partially blocked by caspase-8 and caspase-9 inhibitors. Stable maspin-expressing transfectants, TUNEL assay, Western blot, RPA for Bcl-2 family, caspase inhibitor experiments BMC cancer Medium 15907209
2005 Targeted intravascular expression of maspin in endothelial cells induces endothelial cell apoptosis in vitro and in vivo, disrupting tumor-induced angiogenesis; the pro-apoptotic effect requires the RSL region of maspin and is accompanied by changes in Bcl-2 family gene expression and is blocked by caspase inhibitors and Bcl-2 overexpression. Adenoviral maspin delivery in mice bearing mammary tumors, in vitro HUVEC apoptosis assay, RSL-deletion mutant, Bcl-2 overexpression rescue, caspase inhibitor experiments Oncogene High 15688005
2003 Maspin regulates cell motility through the Rho GTPase pathway: exogenous recombinant maspin decreases Rac1 activity within 4 h and reduces its effector PAK1 within 12 h in MDA-MB-231 breast cancer cells; adhesion increase is mediated by PI3K/ERK pathways and is abrogated by LY294002. Recombinant maspin treatment, stable transfection, Rac1 pull-down, PI3K inhibitor (LY294002), ERK kinase assay, focal adhesion staining Cancer biology & therapy Medium 14508113
2011 Maspin directly inhibits HDAC1, increasing Ku70 acetylation and dissociation of Bax from Ku70, thereby promoting Bax translocation to mitochondria and apoptosis in cancer cells. Co-IP (maspin–Ku70 interaction), HDAC1 activity assay, Ku70 acetylation Western blot, Bax–Ku70 dissociation assay, cell death measurements International journal of molecular medicine Medium 22076034
2008 Maspin suppresses hypoxia-induced prostate cancer cell survival and tumor vascularity by targeting Akt and focal adhesion kinase (FAK) activation, as shown in maspin-overexpressing DU-145 cells exposed to 1% O₂ and in in vivo tumor studies. Maspin-overexpressing stable transfectants, hypoxia exposure (1% O₂), Akt/FAK phosphorylation Western blot, in vivo tumor implantation Oncogene Medium 18931702
2009 In response to hypoxia, cytoplasmic PTEN prevents Mdm2 nuclear localization (by attenuating Akt) while nuclear PTEN complexes with p53 to coordinately induce maspin transcription; loss of PTEN or p53 individually attenuates hypoxia-induced maspin expression in glioblastoma cells. PTEN/p53 knockdown and reconstitution in U87 cells, subcellular fractionation, Co-IP (PTEN–p53 complex), in vivo xenograft IHC Cell cycle (Georgetown, Tex.) Medium 19221500
2012 Snail transcription factor directly represses maspin promoter activity by binding to the maspin promoter, as confirmed by ChIP; Snail overexpression increases and Snail knockdown decreases maspin expression, with corresponding changes in migration and invasion in prostate cancer cells. Luciferase reporter assay, ChIP, RT-PCR, Western blot, siRNA knockdown, stable overexpression, migration/invasion assays BMC cancer Medium 22857708
2010 PAR-1 (thrombin receptor) negatively regulates maspin transcription in metastatic melanoma by decreasing binding of Ets-1 and c-Jun to the maspin promoter via reduced CBP/p300 levels and increased p38 activity; PAR-1 silencing restored maspin expression, reduced invasion, tumor growth, and experimental lung metastasis. PAR-1 siRNA nanoliposome delivery, ChIP for Ets-1/c-Jun at maspin promoter, CBP/p300 and p38 expression analysis, in vivo lung metastasis model, maspin rescue experiments Proceedings of the National Academy of Sciences of the United States of America High 21187389
2012 Maspin regulates cell cycle progression by influencing CDC25C and CDK1 activity; maspin downregulation (by shRNA or E2F1-DP1 overexpression) in MKN45 cells accelerated cell cycle progression with increased active CDC25C and decreased inactive CDK1, while maspin upregulation had the opposite effect. shRNA knockdown, stable overexpression, cell cycle analysis, CDC25C/CDK1 phosphorylation Western blot, promoter haplotype reporter assay Carcinogenesis Medium 22962304
2011 SerpinB5/maspin interacts with KHDRBS3 and FBXO32 in gastric cancer cells, as identified by yeast two-hybrid screening and validated by co-immunoprecipitation; KHDRBS3 also interacts with FBXO32 mRNA (RNA Co-IP), and changes in SerpinB5 expression affect FBXO32 mRNA levels through KHDRBS3 protein. Yeast two-hybrid, co-immunoprecipitation, RNA co-immunoprecipitation, Western blot, real-time PCR Oncology reports Medium 21725612
2008 A Pro176Ser polymorphism in maspin located near the reactive site loop reduces its tumor suppressor function: cells expressing Ser176 maspin showed decreased apoptosis, increased colony formation, and higher in vivo tumor formation rate compared to Pro176 maspin. Stable expression of polymorphic variants, apoptosis assay, colony formation assay, mouse tumor formation assay, structural modeling International journal of molecular medicine Medium 18698492
2002 Maspin gene silencing in breast cancer cells is caused by CpG promoter hypermethylation and histone deacetylation; treatment with 5-aza-2'-deoxycytidine and/or trichostatin A restores maspin promoter activity and expression in maspin-negative breast cancer cell lines. Promoter reporter assay, 5-aza-dC treatment, TSA treatment, RT-PCR Biochemical and biophysical research communications Medium 12220518
2003 Maspin expression in human pancreatic carcinoma cells is activated by epigenetic derepression: maspin-positive pancreatic cancer cells have unmethylated promoters with hyperacetylated H3/H4 histones, whereas maspin-negative cells have methylated promoters with hypoacetylated histones; 5-aza-dC treatment activates maspin in negative lines. Bisulfite genomic sequencing, ChIP (H3/H4 acetylation), 5-aza-dC treatment, RT-PCR Neoplasia (New York, N.Y.) High 14670180
2004 Tamoxifen induces maspin expression through estrogen receptor alpha (ERα) but not ERβ; the ERα N-terminal AF-1 domain is required for basal maspin transcription and the LBD-AF2 domain is required for tamoxifen-induced activation; binding occurs via cofactor recruitment to a region between -90 and +87 bp, not through the HRE site. Promoter reporter assay, ERα/ERβ reconstitution, ERα deletion/point mutants, transient transfection in multiple cell lines Cancer letters Medium 15145521
2008 IFIXα induces maspin expression by promoting polyubiquitination and proteasomal degradation of HDAC1 protein (without affecting HDAC1 mRNA), thereby derepressing the maspin promoter; knockdown of maspin abrogates IFIXα-mediated suppression of breast cancer cell invasion. siRNA knockdown, Western blot, HDAC1 ubiquitination assay, proteasome inhibitor rescue, promoter reporter assay Molecular carcinogenesis Medium 18247378
2020 Class I HDACs (HDAC1 and HDAC8) repress maspin in prostate cancer cells independently of promoter DNA hypermethylation; HDAC inhibitors (sodium butyrate, TSA) restore maspin expression accompanied by increased H3/H4 acetylation and p53 enrichment at the maspin promoter, leading to suppression of proliferation and migration. HDAC inhibitor treatment, Western blot, ChIP (H3/H4 acetylation, p53 occupancy), RT-PCR, proliferation and migration assays Molecular carcinogenesis Medium 32391971
2017 Maspin is secreted as an exosomal cargo protein encapsulated within the exosomal membrane; maspin knockdown in MCF-10A cells produces maspin-devoid exosomes with significantly reduced suppressive effects on chemotaxis of recipient NIH3T3 fibroblasts, demonstrating a paracrine tumor-suppressive function of exosomal maspin. Exosome isolation, electron microscopy, atomic force microscopy, Western blot, maspin shRNA knockdown, NIH3T3 chemotaxis assay Oncotarget Medium 28009978
2014 Exogenously applied recombinant maspin (rMaspin) is internalized by multiple endocytic pathways into endosomal/lysosomal vesicles in cancer cells, as shown by real-time laser scanning confocal microscopy with dye-labeled protein; this lysosomal processing reduces biological activity of exogenous maspin compared with endogenously re-expressed maspin. Time-lapse laser scanning confocal microscopy with fluorescently labeled rMaspin, endocytic pathway inhibitors, co-localization with endosomal/lysosomal markers Molecular cancer research : MCR Medium 25256709
2021 Cytoplasmic maspin in aggressive breast cancer cells (MDA-MB-231) promotes cell proliferation and invasion by upregulating SRGN, activating TGFβ signaling, and inducing EMT markers (N-cadherin and EMT transcription factors); nuclear maspin in normal epithelial cells has the opposite tumor-suppressive function. Stable maspin overexpression/knockdown in MDA-MB-231, Western blot for EMT markers and TGFβ pathway, SRGN protein level measurement, proliferation and invasion assays Scientific reports Medium 34059749
2024 SERPINB5 overexpression in CRC cells activates the TNF-α/NF-κB pathway (upregulating p-NF-κB/p65, TNF-α, N-cadherin, MMP2, MMP9, VEGFA; downregulating E-cadherin), promoting EMT, angiogenesis, and invasion/migration; these effects are reversed by QNZ, a specific NF-κB inhibitor. Lentiviral overexpression and knockdown, Western blot, migration/invasion/proliferation assays, HUVEC tube formation assay, NF-κB inhibitor (QNZ) rescue International immunopharmacology Medium 38460302
2001 Maspin is synthesized by normal human corneal stromal cells (the first non-epithelial cell type shown to do so); exogenous recombinant maspin increases adhesion of late-passage (maspin-negative) corneal stromal cells to fibronectin, type I collagen, type IV collagen, and laminin. Western blot, RT-PCR, immunofluorescence microscopy, recombinant maspin adhesion assay on multiple ECM substrates Investigative ophthalmology & visual science Medium 11726614
2015 HBx (hepatitis B virus X protein) induces miR-7, miR-107, and miR-21 which directly target maspin mRNA, reducing maspin protein and promoting HCC cell motility and resistance to anoikis and chemotherapy. miRNA overexpression/inhibition, luciferase reporter for miRNA-target validation, HBx overexpression, Western blot, cell motility and anoikis assays Oncotarget Medium 26296971

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 Nuclear cytokine-activated IKKalpha controls prostate cancer metastasis by repressing Maspin. Nature 358 17377533
2000 p53 regulates the expression of the tumor suppressor gene maspin. The Journal of biological chemistry 237 10692390
2002 The paradoxical expression of maspin in ovarian carcinoma. Clinical cancer research : an official journal of the American Association for Cancer Research 170 12231537
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
2000 High tumoral maspin expression is associated with improved survival of patients with oral squamous cell carcinoma. Oncogene 129 10828881
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
2013 Role of maspin in cancer. Clinical and translational medicine 92 23497644
2012 Maspin: molecular mechanisms and therapeutic implications. Cancer metastasis reviews 83 22752408
2010 Ezrin, maspin, peroxiredoxin 2, and heat shock protein 27: potential targets of a streptococcal-induced autoimmune response in psoriasis. Journal of immunology (Baltimore, Md. : 1950) 80 20363977
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
2010 Caspase 8 and maspin are downregulated in breast cancer cells due to CpG site promoter methylation. BMC cancer 65 20132554
2005 Elevated nuclear maspin expression is associated with microsatellite instability and high tumour grade in colorectal cancer. The Journal of pathology 65 15714592
2003 Maspin regulates different signaling pathways for motility and adhesion in aggressive breast cancer cells. Cancer biology & therapy 63 14508113
2005 Maspin overexpression modulates tumor cell apoptosis through the regulation of Bcl-2 family proteins. BMC cancer 58 15907209
2001 Association of maspin expression with the malignancy grade and tumor vascularization in breast cancer tissues. Cancer letters 57 11485832
2002 Hypermethylation and histone deacetylation lead to silencing of the maspin gene in human breast cancer. Biochemical and biophysical research communications 55 12220518
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
2011 Wogonin, an active ingredient of Chinese herb medicine Scutellaria baicalensis, inhibits the mobility and invasion of human gallbladder carcinoma GBC-SD cells by inducing the expression of maspin. Journal of ethnopharmacology 46 21855619
2006 Epigenetic regulation of maspin expression in human ovarian carcinoma cells. Gynecologic oncology 44 16457875
2004 Disruption of cell-type-specific methylation at the Maspin gene promoter is frequently involved in undifferentiated thyroid cancers. Oncogene 44 14743202
1997 Gamma linolenic acid regulates expression of maspin and the motility of cancer cells. Biochemical and biophysical research communications 43 9299418
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
2001 Maspin: synthesis by human cornea and regulation of in vitro stromal cell adhesion to extracellular matrix. Investigative ophthalmology & visual science 42 11726614
2006 Epigenetic regulation of maspin expression in the human placenta. Molecular human reproduction 41 16936308
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
2004 Aberrant expression of the maspin gene associated with epigenetic modification in melanoma cells. The Journal of investigative dermatology 38 15086568
2004 The promise and challenge toward the clinical application of maspin in cancer. Frontiers in bioscience : a journal and virtual library 38 15353310
2002 Maspin expression in normal skin and usual cutaneous carcinomas. Virchows Archiv : an international journal of pathology 36 12461611
2003 Nitric oxide regulation of maspin expression in normal mammary epithelial and breast cancer cells. The American journal of pathology 34 12707024
2012 Antiandrogenic, maspin induction, and antiprostate cancer activities of tanshinone IIA and its novel derivatives with modification in ring A. Journal of medicinal chemistry 33 22175694
2010 MALDI-TOF mass array analysis of RASSF1A and SERPINB5 methylation patterns in human placenta and plasma. Biology of reproduction 33 20075396
2003 Role of maspin in tumor metastasis and angiogenesis. Current molecular medicine 33 14601639
2016 TMEM45A, SERPINB5 and p16INK4A transcript levels are predictive for development of high-grade cervical lesions. American journal of cancer research 32 27508094
2006 A role of novel serpin maspin in tumor progression: the divergence revealed through efforts to converge. Journal of cellular physiology 32 17001674
2015 miRNA-7/21/107 contribute to HBx-induced hepatocellular carcinoma progression through suppression of maspin. Oncotarget 31 26296971
2012 Snail transcription factor negatively regulates maspin tumor suppressor in human prostate cancer cells. BMC cancer 31 22857708
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
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
2024 SERPINB5 promotes colorectal cancer invasion and migration by promoting EMT and angiogenesis via the TNF-α/NF-κB pathway. International immunopharmacology 28 38460302
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
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
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
2011 Highly increased maspin expression corresponds with up-regulation of miR-21 in endometrial cancer: a preliminary report. International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 25 21330826
2007 Maspin controls mammary tumor cell migration through inhibiting Rac1 and Cdc42, but not the RhoA GTPase. Cell motility and the cytoskeleton 25 17301947
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
2006 Clinical relevance of maspin expression in bladder cancer. World journal of urology 24 16832651
2004 Tamoxifen induces the expression of maspin through estrogen receptor-alpha. Cancer letters 23 15145521
2006 Clinicopathological significance of maspin expression in breast cancer. Journal of Korean medical science 22 16614520
2006 Maspin expression is characteristic for cisplatin-sensitive ovarian cancer cells and for ovarian cancer cases of longer survival rates. International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists 22 16633061
2011 SerpinB5 interacts with KHDRBS3 and FBXO32 in gastric cancer cells. Oncology reports 21 21725612
2008 Maspin, p53, p63, and Ki-67 in epithelial lesions of the tongue: from hyperplasia through dysplasia to carcinoma. Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology 21 18783348
2005 Aberrant expression of maspin in idiopathic inflammatory bowel disease is associated with disease activity and neoplastic transformation. International journal of gastrointestinal cancer 21 16227634
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
2004 Loss of maspin expression is associated with development and progression of gastric carcinoma with p53 abnormality. Oncology reports 21 15492782
2020 Role of class I histone deacetylases in the regulation of maspin expression in prostate cancer. Molecular carcinogenesis 20 32391971
2016 An Essential Role of Maspin in Embryogenesis and Tumor Suppression. Cancer research 20 27923833
2016 IKKα inibition by a glucosamine derivative enhances Maspin expression in osteosarcoma cell line. Chemico-biological interactions 20 27931795
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
2006 Aberrant maspin expression in gallbladder epithelium is associated with intestinal metaplasia in patients with cholelithiasis. Journal of clinical pathology 20 16505288
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
2008 Maspin polymorphism associated with apoptosis susceptibility and in vivo tumorigenesis. International journal of molecular medicine 19 18698492
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
2003 Maspin in thyroid cancer: its relationship with p53 and clinical outcome. Oncology reports 18 14534696
2014 Internalization by multiple endocytic pathways and lysosomal processing impact maspin-based therapeutics. Molecular cancer research : MCR 17 25256709
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
2007 Maspin binds to urokinase-type and tissue-type plasminogen activator through exosite-exosite interactions. The Journal of biological chemistry 16 17510061
2008 Interferon-inducible protein IFIXalpha inhibits cell invasion by upregulating the metastasis suppressor maspin. Molecular carcinogenesis 15 18247378
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
2024 miR-1204 Positioning in 8q24.21 Involved in the Tumorigenesis of Colorectal Cancer by Targeting MASPIN. Protein and peptide letters 14 39082173
2021 Role of cytoplasmic localization of maspin in promoting cell invasion in breast cancer with aggressive phenotype. Scientific reports 14 34059749
2012 Tumor suppressor maspin as a rheostat in HDAC regulation to achieve the fine-tuning of epithelial homeostasis. Critical reviews in eukaryotic gene expression 14 23140166
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
2007 Gum mastic increases maspin expression in prostate cancer cells. Acta pharmacologica Sinica 13 17376297