Affinage

SPAG9

C-Jun-amino-terminal kinase-interacting protein 4 · UniProt O60271

Length
1321 aa
Mass
146.2 kDa
Annotated
2026-04-28
81 papers in source corpus 23 papers cited in narrative 22 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SPAG9 is a JIP-like scaffold protein that organizes MAPK signaling — principally the JNK and p38 cascades — to control cell proliferation, survival, migration, and differentiation in diverse tissues. It binds JNK2 and JNK3 preferentially through a dedicated JNK-binding domain and requires leucine-zipper/coiled-coil and transmembrane domains for dimerization and proper subcellular localization; in cancer cells, SPAG9 sustains JNK-JunD, MKK3-p38-ELK1, and downstream MMP9/cyclin D1 signaling to drive proliferation, invasion, and epithelial-mesenchymal transition, while its loss triggers mitochondrial apoptosis and senescence (PMID:15693750, PMID:27698841, PMID:27042099, PMID:27449044). In the testis, SPAG9 localizes to the sperm acrosome and relocates to the equatorial segment after the acrosome reaction, where it participates in sperm–egg binding (PMID:15693750, PMID:16143403). Biallelic loss-of-function variants in SPAG9 cause a multisystem human developmental syndrome featuring coarse facies, albinism, cataracts, skeletal abnormalities, and developmental delay (PMID:39846792).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2005 High

    Establishing SPAG9 as a JNK scaffold: the protein was shown to contain a JNK-binding domain with selectivity for JNK2/3 over JNK1 and no interaction with p38α or ERK, resolving its position in the MAPK hierarchy and defining the domain requirements (leucine zipper/coiled-coil and transmembrane) for dimerization and localization.

    Evidence Co-immunoprecipitation, deletion-mutant transfection, CD spectroscopy, and tandem MS in mammalian cells

    PMID:15693750

    Open questions at the time
    • Crystal or cryo-EM structure of the SPAG9–JNK complex is lacking
    • Whether SPAG9 directly scaffolds upstream MKKs alongside JNK was not tested
    • In vivo relevance of JNK isoform selectivity not established
  2. 2005 High

    Linking SPAG9 to sperm function: the protein localizes to the acrosome in intact spermatozoa, redistributes to the equatorial segment after the acrosome reaction, and anti-SPAG9 antibodies block sperm–egg binding, establishing a direct role in fertilization.

    Evidence Indirect immunofluorescence, Western blot of sperm extracts, hemizona binding assay across primate species

    PMID:15293220 PMID:15693750 PMID:16143403

    Open questions at the time
    • The oocyte-side receptor for SPAG9 is unknown
    • Whether SPAG9's JNK scaffold function is relevant in spermatozoa is unresolved
    • Genetic knockout in a model organism was not performed
  3. 2009 Medium

    Demonstrating pro-tumorigenic function: SPAG9 knockdown in cervical cancer cells suppressed growth, colony formation, migration, invasion, and xenograft tumor growth, providing the first direct evidence that SPAG9 is required for cancer cell proliferation and metastatic behavior.

    Evidence Plasmid-based siRNA knockdown with in vitro assays and nude mouse xenograft model

    PMID:19813278

    Open questions at the time
    • The specific downstream signaling pathway was not dissected in this system
    • Rescue by SPAG9 re-expression was not shown
    • Off-target siRNA effects not controlled by multiple independent sequences
  4. 2013 Medium

    Placing SPAG9 upstream of JNK activation and MMP9: knockdown in lung cancer and astrocytoma cells reduced phospho-JNK and MMP9 expression without altering TIMP1/2, linking SPAG9's scaffold activity to a specific protease effector that drives invasion.

    Evidence siRNA knockdown with Western blot, RT-PCR, and invasion assays across multiple cancer cell lines

    PMID:23696027 PMID:23711689

    Open questions at the time
    • Whether SPAG9 directly scaffolds the kinase cascade leading to MMP9 transcription or acts indirectly was not resolved
    • MMP9 enzymatic activity (e.g., zymography) was not always measured
  5. 2014 Medium

    Expanding downstream effectors to cell-cycle regulators and angiogenic factors: SPAG9 overexpression upregulated cyclin D1/E in prostate cancer cells, and knockdown reduced MMP-2/9, increased TIMPs, and decreased VEGF secretion/tube formation, broadening the functional output of SPAG9 beyond invasion to proliferation and angiogenesis.

    Evidence Gain- and loss-of-function in prostate cancer cells with Western blot, ELISA, and tube formation assay

    PMID:24740566 PMID:25310386

    Open questions at the time
    • Direct regulation of cyclin D1 promoter by SPAG9-dependent transcription factors not shown
    • VEGF regulation pathway (JNK-dependent vs. JNK-independent) not delineated
  6. 2015 High

    Identifying an oncogenic SPAG9::JAK2 fusion: a t(9;17)(p24;q21) translocation in B-ALL produced a SPAG9::JAK2 fusion protein with constitutive JAK2 kinase and STAT3/5 phosphorylation, revealing how SPAG9's coiled-coil domain can drive oligomerization-dependent kinase activation.

    Evidence Paired-end transcriptome sequencing of primary ALL, Ba/F3 retroviral transduction with phospho-JAK2/STAT Western blot

    PMID:25951811

    Open questions at the time
    • Frequency of SPAG9::JAK2 fusions across leukemia subtypes unknown
    • Whether wild-type SPAG9 influences JAK-STAT signaling was not tested
  7. 2016 Medium

    Defining SPAG9's role in apoptosis suppression and EMT: comprehensive molecular profiling after knockdown in triple-negative breast cancer showed upregulation of pro-apoptotic BCL-2 family members and E-cadherin, and downregulation of anti-apoptotic proteins (BCL-2, MCL-1, XIAP), EMT transcription factors (SLUG, SNAIL, TWIST), and mesenchymal markers, establishing SPAG9 as a dual pro-survival and pro-EMT factor.

    Evidence shRNA knockdown with flow cytometry, Western blot panel, and in vivo xenograft

    PMID:27449044

    Open questions at the time
    • Which of these changes are direct versus indirect consequences of SPAG9 loss is unknown
    • Whether the EMT program requires JNK versus p38 was not distinguished
  8. 2016 Medium

    Delineating the SPAG9–p38–ELK1 axis: in hepatocellular carcinoma, SPAG9 knockdown inhibited p38 signaling and ELK1 expression, and ELK1 overexpression rescued SPAG9-depleted cells, positioning ELK1 as a key effector downstream of SPAG9/p38 in metastasis.

    Evidence siRNA knockdown combined with ELK1 rescue, wound healing, invasion, and Western blot in HCC cells

    PMID:27042099

    Open questions at the time
    • Direct binding of SPAG9 to p38 pathway components was not shown (Co-IP showed JNK binding, initial study found no p38α interaction)
    • Contribution of JNK vs. p38 to ELK1 regulation not separated
  9. 2016 Medium

    Confirming JNK-JunD as a SPAG9-dependent signaling module: a JNK inhibitor abolished SPAG9-induced JunD upregulation in osteosarcoma cells, providing pharmacological evidence that SPAG9 signals through JNK to activate JunD-dependent proliferation and invasion.

    Evidence JNK inhibitor SP600125 in combination with SPAG9 overexpression/knockdown, Western blot for p-JNK, JunD, cyclin D1

    PMID:27698841

    Open questions at the time
    • Whether JunD is a direct transcriptional target of JNK-phosphorylated substrates or acts indirectly was not resolved
    • Other AP-1 family members were not tested
  10. 2019 Medium

    Establishing ceRNA regulation of SPAG9: multiple lncRNAs (NEAT1, H19, later ZSCAN16-AS1) were shown to sponge specific miRNAs (miR-9-5p, miR-141, miR-181c-5p) that directly target the SPAG9 3′UTR, identifying post-transcriptional control of SPAG9 abundance as a mechanism governing JNK/p38 pathway output in cancer, drug resistance, and stem cell differentiation.

    Evidence Dual-luciferase reporter, RNA immunoprecipitation, RNA pull-down, and functional rescue across thyroid carcinoma, HCC, and dental stem cells

    PMID:30755596 PMID:31485599 PMID:34097562

    Open questions at the time
    • Endogenous stoichiometry of miRNA sponging has not been quantified
    • Whether these ceRNA circuits operate outside the specific cell types tested is unknown
  11. 2022 High

    Mechanistic dissection of SPAG9::JAK2 oncogenic signaling: kinase-domain tyrosine mutagenesis abolished IL-3-independent growth and STAT1 phosphorylation; STAT1 was shown to induce BCL-2 and MCL-1, and combination of ruxolitinib with BCL-2/MCL-1 inhibitors synergistically killed fusion-expressing cells, defining a targetable JAK2–STAT1–BCL-2/MCL-1 circuit.

    Evidence Ba/F3 retroviral reconstitution with site-directed mutagenesis, gene expression profiling, pharmacological combination assays, in vivo mouse model

    PMID:35879405

    Open questions at the time
    • Clinical validation of the ruxolitinib/BCL-2 inhibitor combination in patients with SPAG9::JAK2-positive ALL is lacking
    • Whether STAT1-driven BCL-2/MCL-1 is unique to this fusion or shared with other JAK2 fusions is unknown
  12. 2025 Medium

    Linking SPAG9 loss-of-function to human developmental disease: biallelic frameshift variants in two families caused a multisystem syndrome (coarse facies, albinism, cataracts, skeletal abnormalities, developmental delay), with confirmed SPAG9 mRNA depletion, establishing SPAG9 as essential for human development beyond its known roles in germ cells and cancer.

    Evidence Whole-genome sequencing, Sanger segregation in two independent families, RT-qPCR of patient samples

    PMID:39846792

    Open questions at the time
    • Animal model recapitulating the syndrome has not been reported
    • Which SPAG9-dependent signaling pathways underlie the developmental phenotypes is unknown
    • Only one truncating variant has been described; allelic series is lacking

Open questions

Synthesis pass · forward-looking unresolved questions
  • The structural basis for SPAG9's scaffold interactions with JNK and putative p38-pathway components remains unresolved, and how the same scaffold supports such diverse tissue-specific outputs (sperm-egg binding, neuronal JNK3 signaling, EMT, osteogenic differentiation, systemic development) is not mechanistically explained.
  • No high-resolution structure of full-length SPAG9 or its complexes exists
  • Genetic knockout/conditional models in mice have not been reported
  • Direct p38 pathway binding partners of SPAG9 have not been biochemically identified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 4 GO:0098772 molecular function regulator activity 3
Localization
GO:0005886 plasma membrane 2 GO:0005829 cytosol 1
Pathway
R-HSA-162582 Signal Transduction 6 R-HSA-1643685 Disease 2 R-HSA-1474165 Reproduction 1 R-HSA-5357801 Programmed Cell Death 1
Partners
ELK1HLA-GJAK2JNK2JNK3MKK3STAT3

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 SPAG9 protein contains a JNK-binding domain and interacts preferentially with JNK3 and JNK2 over JNK1, with no interaction detected with p38α or ERK pathways. Both the leucine zipper/coiled-coil domains and the transmembrane domain are required for dimerization and proper subcellular localization. Co-immunoprecipitation, deletion mutant transfection, CD spectroscopy, tandem MS, indirect immunofluorescence The Biochemical journal High 15693750
2005 SPAG9 protein localizes to the acrosomal compartment of intact human spermatozoa and relocates to the equatorial segment after the acrosome reaction; anti-SPAG9 antibodies inhibit sperm binding to intact human oocytes and hemizonae. Indirect immunofluorescence, Western blot of sperm extracts, hemizona binding assay The Biochemical journal High 15293220 15693750 16143403
2009 siRNA-mediated knockdown of SPAG9 in SiHa cervical squamous cell carcinoma cells inhibits cell growth, colony formation, migration, and invasion in vitro, and significantly suppresses tumor growth in a cervical cancer xenograft model in nude mice. Plasmid-based siRNA knockdown, colony formation assay, migration/invasion assays, xenograft tumor model Cancer Medium 19813278
2013 SPAG9 knockdown in non-small cell lung cancer cells inhibits cell growth and invasion and is accompanied by downregulation of MMP9 mRNA/protein and inhibition of JNK phosphorylation, placing SPAG9 upstream of JNK activation and MMP9 expression. siRNA knockdown, Western blot, RT-PCR, cell growth and invasion assays Lung cancer (Amsterdam, Netherlands) Medium 23711689
2013 SPAG9 knockdown in triple-negative breast cancer cells (MDA-MB-231) reduces proliferation, colony formation, migration, invasion, and tumor growth in nude mice xenografts; SPAG9 is predominantly localized in the cytoplasm with surface expression also detected. siRNA knockdown, IIF, FACS, MTT, invasion assay, xenograft model Journal of experimental & clinical cancer research Medium 24330581
2013 SPAG9 knockdown in astrocytoma cell lines reduces cell proliferation and invasion accompanied by downregulation of MMP9, without changes in TIMP1 or TIMP2, suggesting SPAG9 regulates invasion through MMP9. siRNA knockdown, MTT assay, Matrigel invasion assay, Western blot, RT-PCR Tumour biology Medium 23696027
2014 SPAG9 knockdown in prostate cancer cells inhibits motility and invasion through inactivation of MMP-2/MMP-9 accompanied by upregulation of TIMP-1/TIMP-2; SPAG9 silencing also reduces VEGF secretion and tube formation, linking SPAG9 to angiogenesis. siRNA knockdown, Matrigel invasion assay, Western blot, ELISA, tube formation assay Oncology reports Medium 25310386
2014 SPAG9 overexpression promotes prostate cancer cell proliferation and regulates cyclin D1 and cyclin E protein levels; siRNA knockdown of SPAG9 inhibits proliferation. Plasmid transfection, siRNA knockdown, colony formation, MTT assay, Western blot Tumour biology Medium 24740566
2015 A novel SPAG9-JAK2 fusion gene was identified in B-cell precursor ALL with t(9;17)(p24;q21) by paired-end transcriptome sequencing; cells expressing SPAG9::JAK2 showed constitutive phosphorylation of JAK2 kinase domain tyrosines and STAT3/STAT5. Paired-end transcriptome sequencing, Ba/F3 retroviral transduction, Western blot for phospho-JAK2/STAT3/STAT5 Genes, chromosomes & cancer High 25951811 35879405
2016 SPAG9 ablation (shRNA) in triple-negative breast cancer cells induces mitochondrial membrane potential changes, DNA fragmentation, caspase activation, G0-G1 arrest, and cellular senescence; upregulates BAK, BAX, BIM, BID, NOXA, AIF, Cyto-C, PARP1, APAF1, caspase 3/9, and E-cadherin; downregulates cyclin B1, D1, E, CDK1/4/6, BCL2, BCL-xL, XIAP, cIAP2, MCL1, and EMT markers (SLUG, SNAIL, TWIST, vimentin, N-cadherin, MMP2/3/9, β-catenin). In vivo xenograft studies confirmed tumor suppression. shRNA knockdown, flow cytometry, Western blot, in vivo xenograft Tumour biology Medium 27449044
2016 SPAG9 knockdown in hepatocellular carcinoma cells suppresses cell migration and invasion and inhibits ELK1 expression and p38 signaling; ELK1 overexpression reverses the inhibitory effects of SPAG9 siRNA on HCC cell metastasis, placing SPAG9 upstream of ELK1 in the p38 pathway. siRNA knockdown, plasmid overexpression, wound healing, Matrigel invasion, Western blot, immunohistochemistry OncoTargets and therapy Medium 27042099
2018 SPAG9 overexpression in bladder cancer cells promotes migration through upregulation of HEF1 and activation of Rac1; SPAG9 silencing reduces HEF1 and Rac1 activity and inhibits migration. SPAG9 also regulates EMT markers E-cadherin and vimentin. Overexpression/siRNA knockdown, Western blot for Rac1 activation, migration assay, qRT-PCR American journal of cancer research Medium 30662804
2019 SPAG9 co-immunoprecipitates with JNK in liver cancer (HepG2) cells; SPAG9 knockdown decreases expression of JNK, p38, and MKK3, identifying the SPAG9/MKK3/p38 axis as a regulator of liver cancer cell proliferation, apoptosis, and cell cycle. Co-immunoprecipitation, siRNA knockdown, Western blot, CCK-8 proliferation assay, flow cytometry Oncology reports Medium 30720101
2019 SPAG9 promotes prostate cancer cell proliferation, migration, motility, and cell cycle progression via the MAPK signaling pathway; SPAG9 knockout in nude mice suppresses tumor growth in vivo. Overexpression/knockdown/knockout, Western blot for MAPK pathway markers, migration assay, xenograft model American journal of translational research Medium 31497238
2016 SPAG9 is overexpressed in osteosarcoma and positively regulates cyclin D1, phosphorylated JNK, and JunD expression; treatment with the JNK inhibitor SP600125 abolishes SPAG9-induced upregulation of JunD, demonstrating SPAG9 functions through JNK-JunD signaling to promote proliferation and invasion. siRNA knockdown, plasmid transfection, MTT assay, Matrigel invasion assay, Western blot, JNK inhibitor experiment Oncology letters Medium 27698841
2022 Ba/F3 cells expressing SPAG9::JAK2 fusion proliferate independently of IL-3 and show constitutive phosphorylation of JAK2 kinase domain tyrosines, STAT3, STAT5, and STAT1; mutation of kinase domain tyrosines abolishes IL-3 independence and STAT1 phosphorylation. STAT1 induces BCL-2 and MCL-1 expression, and combination of ruxolitinib with BCL-2/MCL-1 inhibitors synergistically suppresses SPAG9::JAK2-driven proliferation. Retroviral transduction of Ba/F3 cells, kinase domain mutagenesis, Western blot for phosphoproteins, gene expression analysis, pharmacological inhibitor combination assays, in vivo mouse model Cancer gene therapy High 35879405
2023 HLA-G functions in an HLA-G/SPAG9/STAT3 axis to promote establishment of brain metastatic lesions; premetastatic brain metastasis initiating cells exhibit elevated HLA-G and SPAG9 expression, and disruption of this axis impairs brain metastasis. RNA sequencing of premetastatic vs. macrometastatic BMICs, functional validation of HLA-G/SPAG9/STAT3 axis Proceedings of the National Academy of Sciences of the United States of America Medium 36780531
2021 ZSCAN16-AS1 acts as a competing endogenous RNA (ceRNA) to sponge miR-181c-5p, thereby de-repressing SPAG9 expression; SPAG9 in turn activates the JNK pathway to drive HCC cell proliferation, migration, and invasion. RIP and RNA pull-down assays confirmed ZSCAN16-AS1/miR-181c-5p and luciferase assay confirmed miR-181c-5p/SPAG9 interactions. RNA immunoprecipitation, RNA pull-down, luciferase reporter assay, siRNA knockdown, Western blot, colony formation, transwell assay Cell cycle (Georgetown, Tex.) Medium 34097562
2019 NEAT1 lncRNA sponges miR-9-5p, which directly targets SPAG9; NEAT1 silencing reduces DDP resistance of anaplastic thyroid carcinoma cells via the miR-9-5p/SPAG9 axis in vitro and in vivo, confirmed by dual-luciferase reporter and RIP assays. Dual-luciferase reporter assay, RNA immunoprecipitation, siRNA knockdown, qRT-PCR, Western blot, animal model International journal of oncology Medium 31485599
2019 LncRNA H19 competitively binds miR-141, preventing miR-141-mediated degradation of SPAG9, thereby elevating phosphorylated p38 and JNK and facilitating osteogenic/odontogenic differentiation of stem cells from apical papilla. Lentiviral overexpression/knockdown, Western blot, ALP activity, alizarin red staining, in vivo bone formation assay, molecular sponge mechanism assays Cell death & disease Medium 30755596
2025 Biallelic frameshift variant (c.903del; p.Phe301Leufs*2) in SPAG9 causes a multisystem syndrome (coarse facial features, albinism, cataracts, skeletal abnormalities, developmental delay) in two human families; RT-qPCR confirmed marked reduction of SPAG9 mRNA in affected individuals, establishing a loss-of-function role for SPAG9 in systemic human development. Whole genome sequencing, Sanger sequencing segregation, RT-qPCR, 3D protein modeling Genetics and molecular biology Medium 39846792
2009 SPAG9 protein is expressed in human ejaculated spermatozoa and localizes to the equatorial plate and flagella (distinct from the acrosomal localization in intact spermatozoa), suggesting roles in sperm capacitation and motility. RT-PCR, indirect immunofluorescence of purified spermatozoa Zhonghua nan ke xue Low 19947555

Source papers

Stage 0 corpus · 81 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 A Syd-1 homologue regulates pre- and postsynaptic maturation in Drosophila. The Journal of cell biology 152 20176924
2012 Cooperation of Syd-1 with Neurexin synchronizes pre- with postsynaptic assembly. Nature neuroscience 104 22864612
2002 SYD-1, a presynaptic protein with PDZ, C2 and rhoGAP-like domains, specifies axon identity in C. elegans. Nature neuroscience 92 12379863
2005 Characterization of a novel human sperm-associated antigen 9 (SPAG9) having structural homology with c-Jun N-terminal kinase-interacting protein. The Biochemical journal 74 15693750
2019 LncRNA H19 promotes the committed differentiation of stem cells from apical papilla via miR-141/SPAG9 pathway. Cell death & disease 52 30755596
1996 Role of DNA sequences outside the cores of DNase hypersensitive sites (HSs) in functions of the beta-globin locus control region. Domain opening and synergism between HS2 and HS3. The Journal of biological chemistry 47 8662652
2016 MicroRNA-200a-3p suppresses tumor proliferation and induces apoptosis by targeting SPAG9 in renal cell carcinoma. Biochemical and biophysical research communications 43 26797273
2013 Down regulation of SPAG9 reduces growth and invasive potential of triple-negative breast cancer cells: possible implications in targeted therapy. Journal of experimental & clinical cancer research : CR 35 24330581
2021 Epigenome-wide association study of sarcopenia: findings from the Hertfordshire Sarcopenia Study (HSS). Journal of cachexia, sarcopenia and muscle 34 34862756
2019 LncRNA NEAT1 enhances the resistance of anaplastic thyroid carcinoma cells to cisplatin by sponging miR‑9‑5p and regulating SPAG9 expression. International journal of oncology 33 31485599
2013 Clinical significance and biological roles of SPAG9 overexpression in non-small cell lung cancer. Lung cancer (Amsterdam, Netherlands) 32 23711689
2013 SPAG9 is overexpressed in human astrocytoma and promotes cell proliferation and invasion. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 30 23696027
2009 Small interfering RNA-mediated down-regulation of SPAG9 inhibits cervical tumor growth. Cancer 30 19813278
1984 Stimulation of HTC hepatoma cell growth in vitro by hepatic stimulator substance (HSS). Interactions with serum, insulin, glucagon, epidermal growth factor and platelet derived growth factor. Experimental cell research 30 6363107
2003 Effect of acute ethanol exposure on hepatic stimulator substance (HSS) levels during liver regeneration: protective function of HSS. Digestive diseases and sciences 27 14627336
2014 Drosophila Syd-1, liprin-α, and protein phosphatase 2A B' subunit Wrd function in a linear pathway to prevent ectopic accumulation of synaptic materials in distal axons. The Journal of neuroscience : the official journal of the Society for Neuroscience 25 24948803
2005 Sperm associated antigen 9 (SPAG9): a new member of c-Jun NH2 -terminal kinase (JNK) interacting protein exclusively expressed in testis. The Keio journal of medicine 22 16077255
2005 Removal of arsenic and humic substances (HSs) by electro-ultrafiltration (EUF). Journal of hazardous materials 21 15943938
2004 ERK1/2 contributes negative regulation to STAT3 activity in HSS-transfected HepG2 cells. Cell research 21 15115615
2016 The expression of DAMP proteins HSP70 and cancer-testis antigen SPAG9 in peripheral blood of patients with HCC and lung cancer. Cell stress & chaperones 20 28028759
2005 Characterization of immune response in mice to plasmid DNA encoding human sperm associated antigen 9 (SPAG9). Vaccine 20 16061308
2015 Skeletal muscle morphology in sarcopenia defined using the EWGSOP criteria: findings from the Hertfordshire Sarcopenia Study (HSS). BMC geriatrics 19 26678672
2022 Supervised dimensionality reduction for exploration of single-cell data by HSS-LDA. Patterns (New York, N.Y.) 18 36033591
2016 SPAG9 is involved in hepatocarcinoma cell migration and invasion via modulation of ELK1 expression. OncoTargets and therapy 18 27042099
2014 SPAG9 is overexpressed in human prostate cancer and promotes cancer cell proliferation. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 18 24740566
2013 Tegillarca granosa extract Haishengsu (HSS) suppresses expression of mdr1, BCR/ABL and sorcin in drug-resistant K562/ADM tumors in mice. Advances in medical sciences 18 23729583
2012 Loss of syd-1 from R7 neurons disrupts two distinct phases of presynaptic development. The Journal of neuroscience : the official journal of the Society for Neuroscience 18 23238725
2004 Isolation and characterization of a haploid germ cell specific sperm associated antigen 9 (SPAG9) from the baboon. Molecular reproduction and development 18 15293220
2003 Haemorrhagic smolt syndrome (HSS) in Norway: pathology and associated virus-like particles. Diseases of aquatic organisms 18 12718466
2005 Immunogenicity and contraceptive potential of recombinant human sperm associated antigen (SPAG9). Journal of reproductive immunology 17 16143403
2016 Sperm-associated antigen 9 (SPAG9) promotes the survival and tumor growth of triple-negative breast cancer cells. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 16 27449044
2018 Muscle Mass, Muscle Morphology and Bone Health Among Community-Dwelling Older Men: Findings from the Hertfordshire Sarcopenia Study (HSS). Calcified tissue international 15 29372275
2016 Cancer testis antigen SPAG9 is a promising marker for the diagnosis and treatment of lung cancer. Oncology reports 15 26934841
2015 Identification of SPAG9 as a novel JAK2 fusion partner gene in pediatric acute lymphoblastic leukemia with t(9;17)(p24;q21). Genes, chromosomes & cancer 15 25951811
2004 Effect of hepatic stimulator substance (HSS) on cadmium-induced acute hepatotoxicity in the rat liver. Digestive diseases and sciences 15 15309895
2019 SPAG9 promotes prostate cancer proliferation and metastasis via MAPK signaling pathway. American journal of translational research 14 31497238
2014 SPAG9 expression is increased in human prostate cancer and promotes cell motility, invasion and angiogenesis in vitro. Oncology reports 14 25310386
2005 Recruitment of alkaloid-specific homospermidine synthase (HSS) from ubiquitous deoxyhypusine synthase: Does Crotalaria possess a functional HSS that still has DHS activity? Phytochemistry 13 15935411
2018 MiR-524 inhibits cell proliferation and induces cell apoptosis in thyroid cancer via targeting SPAG9. European review for medical and pharmacological sciences 12 29949157
2016 Erythroid activator NF-E2, TAL1 and KLF1 play roles in forming the LCR HSs in the human adult β-globin locus. The international journal of biochemistry & cell biology 12 27026582
2000 Rotational Spectra of the Thiosulfeno Radical, HSS and DSS, between 0.3 and 0.9 THz. Journal of molecular spectroscopy 12 10712872
2023 The bioceramic sealer iRoot SP promotes osteogenic differentiation of human stem cells from apical papilla via miR-141-3p/SPAG9/MAPK signalling pathway. International endodontic journal 11 37357722
2021 ZSCAN16-AS1 expedites hepatocellular carcinoma progression via modulating the miR-181c-5p/SPAG9 axis to activate the JNK pathway. Cell cycle (Georgetown, Tex.) 11 34097562
2018 Sperm associated antigen 9 (SPAG9) a promising therapeutic target of ovarian carcinoma. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 11 29745297
2018 SPAG9 regulates HEF1 expression and drives EMT in bladder transitional cell carcinoma via rac1 signaling pathway. American journal of cancer research 11 30662804
2007 Effect of sydnone SYD-1, a mesoionic compound, on energy-linked functions of rat liver mitochondria. Chemico-biological interactions 11 17644080
2023 An HLA-G/SPAG9/STAT3 axis promotes brain metastases. Proceedings of the National Academy of Sciences of the United States of America 10 36780531
2019 SPAG9/MKK3/p38 axis is a novel therapeutic target for liver cancer. Oncology reports 10 30720101
2017 Drosophila Syd-1 Has RhoGAP Activity That Is Required for Presynaptic Clustering of Bruchpilot/ELKS but Not Neurexin-1. Genetics 10 29217522
2016 The anti-hyperplasia of mammary gland effect of protein extract HSS from Tegillarca granosa. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 10 27930972
2005 The hepatoprotective effect of hepatic stimulator substance (HSS) against liver regeneration arrest induced by acute ethanol intoxication. Digestive diseases and sciences 10 15745088
2005 Molecular cloning and characterization of the macaque sperm associated antigen 9 (SPAG9): an orthologue of human SPAG9 gene. Molecular reproduction and development 9 15736136
2016 Synergistic and attenuated effect of HSS in combination treatment with docetaxel plus cisplatin in human non-small-cell lung SPC-A-1 tumor xenograft. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 8 27044809
2014 Sperm associated antigen 9 (SPAG9) expression and humoral response in benign and malignant salivary gland tumors. Oncoimmunology 8 25941602
2013 The antioxidant effect of the mesoionic compound SYD-1 in mitochondria. Chemico-biological interactions 7 23867904
2011 Effect of sydnone SYD-1 on certain functions of LPS-stimulated macrophages. Molecular and cellular biochemistry 7 21877148
2016 SPAG9 is overexpressed in osteosarcoma, and regulates cell proliferation and invasion through regulation of JunD. Oncology letters 6 27698841
2015 SPAG9 controls the cell motility, invasion and angiogenesis of human osteosarcoma cells. Experimental and therapeutic medicine 6 26893659
2014 Sydnone SYD-1 affects the metabolic functions of isolated rat hepatocytes. Chemico-biological interactions 6 24836382
2023 An antagonism between Spinophilin and Syd-1 operates upstream of memory-promoting presynaptic long-term plasticity. eLife 5 37767892
2022 The combination of ruxolitinib and Bcl-2/Mcl-1 inhibitors has a synergistic effect on leukemic cells carrying a SPAG9::JAK2 fusion. Cancer gene therapy 5 35879405
2005 The role of hepatic stimulator substance (HSS) on liver regeneration arrest induced by cadmium. In vivo (Athens, Greece) 5 15999536
2005 The effect of hepatic stimulator substance (HSS) on liver regeneration arrest induced by 5-HT2 receptor blockade. In vivo (Athens, Greece) 4 16097436
2025 Truncated SPAG9 as a novel candidate gene for a new syndrome: Coarse facial features, albinism, cataract and developmental delay (CACD syndrome). Genetics and molecular biology 3 39846792
2020 miR-874 inhibits gastric cancer cell proliferation by targeting SPAG9. BMC cancer 3 32503577
2016 SPAG9 promotes endometrial carcinoma cell invasion through regulation of genes related to the epithelial-mesenchymal transition. European journal of gynaecological oncology 3 27352556
2015 SYD-1 Promotes Multiple Developmental Steps Leading to Neuronal Connectivity. Molecular neurobiology 3 26660112
2023 Effects of glucosamine hydrochloride combined with non-steroidal anti-inflammatory drugs on symptoms and HSS scores in patients with knee osteoarthritis. Pakistan journal of pharmaceutical sciences 2 37587699
2023 Effects of glucosamine hydrochloride combined with non-steroidal anti-inflammatory drugs on symptoms and HSS scores in patients with knee osteoarthritis. Pakistan journal of pharmaceutical sciences 2 37606025
2022 Oncolytic Adenovirus with SPAG9 shRNA Driven by DD3 Promoter Improved the Efficacy of Docetaxil for Prostate Cancer. Journal of oncology 2 35535313
2019 Consequences of Haemorrhagic Smolt Syndrome (HSS) for the Immune Status of Atlantic salmon (Salmo salar L.) (Case Study). Biology 2 31861586
2012 Assessment of SPAG9 Transcript in Fine Needle Aspirates of Thyroid Nodules. European thyroid journal 2 24783006
1992 Effects of human HSS on hepatocyte and hepatoma cell proliferation and D-GAL induced acute liver failure. Chinese medical sciences journal = Chung-kuo i hsueh k'o hsueh tsa chih 2 1339157
1985 Migration and colonization of leukemic lymphoblasts in AKR and HSS inbred mice followed by serial enzyme determinations. Cancer biochemistry biophysics 2 4084905
2022 Significance of cancer testis-associated antigens (SPAG9 and FBXO39) in colon cancer. Indian journal of cancer 1 34380828
2022 Oncolytic adenovirus carrying SPAG9-shRNA enhanced the efficacy of docetaxel for advanced prostate cancer. Anti-cancer drugs 1 34561997
2009 [Expression and location of SPAG9 in human ejaculated spermatozoa]. Zhonghua nan ke xue = National journal of andrology 1 19947555
2022 [Corrigendum] SPAG9 expression is increased in human prostate cancer and promotes cell motility, invasion and angiogenesis in vitro. Oncology reports 0 35383860
2021 MiR-524 inhibits cell proliferation and induces cell apoptosis in thyroid cancer via targeting SPAG9. European review for medical and pharmacological sciences 0 34919215
1997 [Anti-virus effect of hepatocyte stimulating substance (HSS) on duck hepatitis B virus in vivo]. Zhonghua shi yan he lin chuang bing du xue za zhi = Zhonghua shiyan he linchuang bingduxue zazhi = Chinese journal of experimental and clinical virology 0 15617240
1987 Further studies on migration and colonization of leukemic lymphoblasts in AKR and HSS inbred mice. Cancer biochemistry biophysics 0 3621139