Affinage

SDCBP

Syntenin-1 · UniProt O00560

Length
298 aa
Mass
32.4 kDa
Annotated
2026-06-10
77 papers in source corpus 34 papers cited in narrative 34 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

SDCBP/MDA-9/Syntenin is a tandem PDZ-domain scaffold that nucleates pro-invasive and pro-metastatic signaling complexes downstream of cell-matrix and growth-factor cues (PMID:18832467, PMID:21828040). Its central mechanism is the PDZ-dependent recruitment of c-Src into an active FAK/c-Src module that drives p38 MAPK and NF-κB activation, anchorage-independent growth, motility, and invasion; both PDZ domains contribute, with PDZ2 dominant for NF-κB and the PDZ binding motif required for the c-Src association (PMID:18832467, PMID:20228839, PMID:28141839). SDCBP couples integrin/fibronectin and collagen adhesion to this output, operating in a reciprocal loop with PKCα to assemble integrin-β1/FAK/c-Src complexes and facilitating plasma-membrane targeting of the ILK-PINCH1-α-parvin and ILK-Akt machinery (PMID:20145126, PMID:21828040). Through its PDZ1 domain it engages EGFR/EGFRvIII to prevent receptor internalization and sustain PI3K-Akt signaling, an interaction reinforced when AURKA binds and phosphorylates SDCBP at Ser131/Thr200 to block its ubiquitin-mediated degradation (PMID:28011764, PMID:32572158). SDCBP also acts as a stabilizing scaffold for oncogenic transcriptional regulators, binding the YAP1 TAD via PDZ1 to suppress CK1δ/ε phosphorylation and β-TrCP-mediated degradation, and disassembling the SCF^FBXO22-BACH1 complex to prevent BACH1 K48-linked polyubiquitination, thereby controlling metastatic gene programs and mitochondrial ETC gene expression (PMID:36828627, PMID:40263598). It promotes EMT and STAT3-driven programs, including PD-L1 upregulation and immune evasion, and modulates the tumor microenvironment via myeloid-derived suppressor cell recruitment (PMID:29572229, PMID:29845474, PMID:40263598). Structure-guided NMR and crystallographic studies of the PDZ1 domain enabled small-molecule (PDZ1i, IVMT-Rx series) and dual-PDZ inhibitors that block the Src, EGFRvIII, and downstream interactions to suppress metastasis across multiple cancers (PMID:28011764, PMID:37721536, PMID:36834839).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 2008 High

    Established the founding mechanism by showing SDCBP physically recruits c-Src through its PDZ domains to assemble an active FAK/c-Src complex driving melanoma invasion and metastasis.

    Evidence Reciprocal Co-IP, antisense adenovirus and c-Src siRNA knockdown, in vivo metastasis model

    PMID:18832467

    Open questions at the time
    • Did not map which PDZ domain residues mediate c-Src binding
    • Downstream effectors of the FAK/c-Src complex not yet defined
  2. 2010 High

    Defined the signaling output of the SDCBP-c-Src interaction by establishing that both PDZ domains (PDZ2 dominant) are required to activate p38 MAPK and NF-κB and to support invasive phenotypes.

    Evidence PDZ domain deletion/point mutants, PP2, c-Src(-/-) cells, NF-κB assays

    PMID:20228839

    Open questions at the time
    • Mechanism linking c-Src to p38 MAPK not fully resolved
    • Direct transcriptional targets of NF-κB not enumerated
  3. 2010 High

    Connected SDCBP to matrix adhesion by showing it forms a reciprocal regulatory loop with PKCα to assemble integrin-β1/FAK/c-Src complexes on fibronectin.

    Evidence PKCα inhibition, siRNA knockdown, Co-IP of integrin-β1/FAK/c-Src, phosphorylation assays

    PMID:20145126

    Open questions at the time
    • Direct PKCα-SDCBP physical interaction not demonstrated
    • How SDCBP expression is controlled by PKCα activity unknown
  4. 2011 High

    Extended the adhesion scaffolding role by showing SDCBP facilitates ILK-Akt and integrin-β1/IPP complex assembly and plasma-membrane translocation during collagen adhesion.

    Evidence Co-IP, plasma membrane fractionation, ILK E359K mutant, siRNA, confocal imaging

    PMID:21828040

    Open questions at the time
    • Whether SDCBP binds ILK directly or via an adaptor not resolved
    • PDZ-domain dependence of ILK-Akt targeting not mapped
  5. 2011 Medium

    Identified a novel non-covalent ubiquitin-binding capability and showed SDCBP is itself ubiquitinated yet stable, hinting at non-proteolytic ubiquitin functions.

    Evidence Yeast two-hybrid (K48R ubiquitin), non-covalent binding assays, PDZ deletion, filopodia imaging

    PMID:21359963

    Open questions at the time
    • Ubiquitin binding not validated in mammalian cells
    • Functional consequence of SDCBP ubiquitination undefined
  6. 2013 Medium

    Linked SDCBP to receptor tyrosine kinase signaling by demonstrating EGFR co-localization and regulation of EGFR/PI3K/AKT/c-Src and EMT markers.

    Evidence Co-IP, immunofluorescence, gain/knockdown, tumor sample logistic regression

    PMID:23873690

    Open questions at the time
    • Direct binding interface with EGFR not mapped
    • Causal ordering of EGFR vs Src activation not established here
  7. 2016 Medium

    Mapped specific PDZ1-domain interactions driving EMT, including TGFβ1 binding that elevates RhoA/Cdc42 and nuclear Slug-HDAC1 transcriptional repression upon EGF stimulation.

    Evidence Co-IP PDZ1 mapping, RhoA/Cdc42 activity assays, nuclear translocation imaging, rescue, in vivo metastasis

    PMID:26561205 PMID:27863394

    Open questions at the time
    • Trigger for SDCBP nuclear translocation incompletely defined
    • Relative contribution of cytoplasmic vs nuclear SDCBP to EMT unresolved
  8. 2016 Medium

    Demonstrated a host/microenvironmental role by showing host SDCBP modulates IL-17A, MDSC and Th17 recruitment, with knockout suppressing tumor growth and metastasis.

    Evidence Global knockout mice, syngeneic and IV B16 models, GEM melanoma model, immune profiling

    PMID:27341128

    Open questions at the time
    • Cell-intrinsic SDCBP signaling in host immune cells not dissected
    • Molecular link from SDCBP to IL-17A not defined
  9. 2016 High

    Achieved druggability by using NMR fragment-based design to create PDZ1i, which blocks SDCBP-EGFRvIII binding and post-radiation invasion in GBM and crosses the blood-brain barrier.

    Evidence NMR-guided design, shRNA, PDZ1i inhibition, Co-IP of SDCBP-EGFRvIII, orthotopic GBM model

    PMID:28011764

    Open questions at the time
    • Off-target PDZ interactions of the inhibitor not fully characterized
    • PDZ2-mediated functions not addressed by PDZ1i alone
  10. 2018 High

    Expanded SDCBP into STAT3-axis biology by showing it binds IGF-1R to activate STAT3-MMP signaling and drives STAT3-Tyr705-dependent PD-L1 upregulation and CD8+ T cell apoptosis.

    Evidence Co-IP, CRISPR KO, STAT3 phosphorylation/inhibition assays, in vivo 4T1 model, flow cytometry

    PMID:29572229 PMID:29845474

    Open questions at the time
    • Whether STAT3 activation is direct or Src/JAK-relayed not clarified
    • Generality of PD-L1 mechanism beyond TNBC untested
  11. 2018 Medium

    Implicated SDCBP in cancer stem cell survival and protective autophagy through FAK/PKC-BCL2 phosphorylation and STAT3/NOTCH1 stemness programs.

    Evidence siRNA/shRNA, kinase inhibitors, autophagy marker westerns, GSC sphere and anoikis assays

    PMID:27472461 PMID:29760085

    Open questions at the time
    • Direct binding partners in the autophagy axis not identified
    • Single-lab evidence for stemness regulation
  12. 2019 Medium

    Placed integrins upstream of Src in SDCBP-driven migration and confirmed PDZ1i efficacy in neuroblastoma metastasis.

    Evidence shRNA, PDZ1i, integrin α6/β4 overexpression rescue, Rho/Rac/Cdc42 assays, in vivo metastasis

    PMID:31406249

    Open questions at the time
    • Mechanism by which SDCBP regulates integrin levels unclear
    • Direct SDCBP-integrin physical interaction not shown
  13. 2020 High

    Revealed post-translational control of SDCBP by showing AURKA phosphorylates it at Ser131/Thr200 to block its ubiquitin-mediated degradation, enabling EGFR-PI3K-Akt activation via blocked EGFR internalization.

    Evidence Co-IP, phospho-site mapping, in vitro kinase assay, ubiquitination and EGFR internalization assays, xenograft

    PMID:32572158

    Open questions at the time
    • Identity of the SDCBP E3 ligase not determined
    • How phosphorylation alters PDZ-EGFR engagement not structurally resolved
  14. 2023 High

    Established SDCBP as a stabilizing scaffold for oncogenic transcription factors by showing PDZ1-dependent stabilization of YAP1 (via CK1δ/ε and β-TrCP inhibition) and disassembly of the SCF-FBXO22-BACH1 ubiquitin-ligase complex.

    Evidence Co-IP, pull-down, K48-ubiquitination assays, domain mapping, organoid/KPC/PDX and TNBC in vivo models

    PMID:36828627 PMID:40263598

    Open questions at the time
    • How a single PDZ1 surface accommodates structurally diverse clients unresolved
    • Whether YAP1 and BACH1 stabilization are competing or coordinate functions unknown
  15. 2023 High

    Advanced therapeutic targeting with dual-PDZ inhibitors and the first crystal structure of the PDZ1-inhibitor complex, validating structure-guided blockade of SDCBP protein-protein interactions.

    Evidence NMR/X-ray crystallography (PDZ1-PI1B), dual-PDZ inhibitor (IVMT-Rx-3), Src Co-IP, fluorescence polarization, in vivo melanoma metastasis with checkpoint combination

    PMID:36834839 PMID:37721536

    Open questions at the time
    • Selectivity across the broader PDZ-domain proteome not fully profiled
    • Clinical translatability of dual-PDZ inhibitors untested
  16. 2023 Medium

    Connected SDCBP to the bone metastatic niche by showing tumor SDCBP supports PDGF-AA secretion that reprograms BM-MSCs via YAP/MST signaling toward immunosuppressive CXCL5.

    Evidence SDCBP knockout tumor cells, conditioned media, YAP/MST signaling assays, in vivo bone metastasis

    PMID:37922327

    Open questions at the time
    • Mechanism linking SDCBP to PDGF-AA expression not defined
    • Single-lab niche model

Open questions

Synthesis pass · forward-looking unresolved questions
  • How SDCBP's PDZ1 surface selects among its many degradation-regulating clients (YAP1, BACH1, EGFR) and how phosphorylation reprograms this client repertoire remains unresolved.
  • No structural model of multi-client PDZ1 binding
  • E3 ligases controlling SDCBP turnover unidentified
  • Physiological (non-cancer) function of SDCBP not addressed in the corpus

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 GO:0008092 cytoskeletal protein binding 2 GO:0140313 molecular sequestering activity 2
Localization
GO:0005829 cytosol 2 GO:0005886 plasma membrane 2 GO:0005634 nucleus 1
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 3 R-HSA-168256 Immune System 3 R-HSA-392499 Metabolism of proteins 3 R-HSA-1474244 Extracellular matrix organization 2
Partners
AURKABACH1EGFRIGF1RILKSRCTGFB1YAP1
Complex memberships
FAK/c-Src signaling complexSCF(FBXO22)-BACH1 ubiquitin-ligase complex (disassembled by SDCBP)integrin-β1/ILK-PINCH1-α-parvin (IPP) complex

Evidence

Reading pass · 34 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2008 MDA-9/Syntenin physically interacts with c-Src via its PDZ domains, and this interaction promotes formation of an active FAK/c-Src signaling complex, leading to enhanced tumor cell invasion and metastatic spread in melanoma. Co-immunoprecipitation, antisense adenovirus knockdown, c-Src siRNA, in vivo metastasis model Proceedings of the National Academy of Sciences of the United States of America High 18832467
2010 MDA-9/Syntenin-c-Src interactions are required for NF-κB activation; both PDZ domains (with PDZ2 dominant) are required. Deletion or point mutations of the PDZ binding motif preventing MDA-9/Syntenin association with c-Src reduce p38 MAPK and NF-κB activation, anchorage-independent growth, motility, and invasion. PDZ domain deletion/point mutation constructs, PP2 (Src inhibitor), siRNA, c-Src(-/-) knockout cell lines, NF-κB activation assays Oncogene High 20228839
2007 MDA-9/Syntenin initiates a signaling cascade activating NF-κB through FAK and p38 MAPK in melanoma cells, promoting MT1-MMP expression and subsequent pro-MMP-2 activation to drive migration and ECM invasion. (NOTE: paper is retracted; confidence downgraded accordingly.) Antisense adenovirus, dominant-negative FAK (FRNK), IκBα super-repressor, invasion and migration assays Cancer research Low 17308124
2010 MDA-9/Syntenin mediates fibronectin (FN)-induced adhesion signaling by forming an interdependent regulatory loop with PKCα: MDA-9/Syntenin expression is required for FN-induced PKCα phosphorylation (Thr638/641), and PKCα activity is required for MDA-9/Syntenin expression; both are required for formation of integrin-β1/FAK/c-Src signaling complexes and downstream p38 MAPK, Cdc42, and NF-κB activation. PKCα inhibition, mda-9/syntenin siRNA knockdown, Co-IP of integrin-β1/FAK/c-Src complexes, phosphorylation assays Cancer research High 20145126
2011 MDA-9/Syntenin regulates Akt activation during adhesion to type I collagen by facilitating association of ILK with Akt and plasma membrane translocation of the ILK-Akt complex; it also facilitates assembly of integrin-β1/IPP (ILK-PINCH1-α-parvin) signaling complexes at the plasma membrane. Co-IP, plasma membrane fractionation, ILK mutant (E359K), mda-9/syntenin siRNA knockdown, fluorescence/confocal imaging The Journal of biological chemistry High 21828040
2011 MDA-9/Syntenin binds ubiquitin non-covalently via a novel ubiquitin-binding motif (not previously described) identified by yeast two-hybrid; it is also itself ubiquitinated but is stable, suggesting ubiquitin interaction is not related to proteolysis. PDZ domain deletion inhibits filopodia formation. Yeast two-hybrid (modified ubiquitin K48R), non-covalent binding assays, PDZ-domain deletion constructs, filopodia imaging Molecular and cellular biochemistry Medium 21359963
2012 MDA-9/Syntenin induces tumor angiogenesis by interacting with the ECM to activate Src and FAK, leading to Akt phosphorylation, HIF-1α induction, and transcriptional activation of IGFBP-2; secreted IGFBP-2 promotes angiogenesis and stimulates endothelial cells to produce VEGF-A. Gain-of-function/loss-of-function genetics, tube formation assay, CAM assay, xenograft model, Co-IP/signaling pathway analysis Cancer research Medium 23233738
2013 MDA-9/Syntenin physically interacts with EGFR (co-localization confirmed in cell lines and primary UCC tumors) and regulates EGFR, AKT, PI3K, and c-Src expression/activation; overexpression alters EMT markers (β-catenin, E-cadherin, vimentin, claudin-1, ZO-1, TCF4). Co-IP, immunofluorescence co-localization, gain-of-function/knockdown, logistic regression with tumor samples Clinical cancer research Medium 23873690
2016 MDA-9/Syntenin uses its PDZ1 domain to interact with TGFβ1; this interaction upregulates active RhoA and Cdc42 levels, driving EMT and invasion in breast cancer cells. Re-introduction of TGFβ1 in MDA-9-silenced cells restores RhoA/Cdc42 activity and partially rescues invasion. Co-IP (PDZ1 domain interaction with TGFβ1), RhoA/Cdc42 activity assays, MDA-9 silencing/overexpression, 2D/3D morphology, in vivo lung metastasis model Oncotarget Medium 27863394
2016 MDA-9/Syntenin translocates to the nucleus upon EGF stimulation, uses its PDZ1 domain to bind Slug transcription factor, recruits HDAC1, and enhances Slug-mediated transcriptional repression, promoting EMT, cancer invasion, and metastasis in lung adenocarcinoma. Co-IP (PDZ1-Slug interaction), HDAC1 recruitment assay, nuclear translocation imaging, PDZ domain mutants, invasion/metastasis assays Oncotarget Medium 26561205
2016 In the tumor microenvironment, host MDA-9/Syntenin expression modulates IL-17A expression and recruitment of myeloid-derived suppressor cells (MDSCs) and Th17 cells; knockout of mda-9/syntenin in host mice suppressed subcutaneous tumor growth and lung metastasis and delayed tumor initiation in a spontaneous melanoma GEM model. Mda-9/syntenin global knockout mice, syngeneic B16 xenograft, IV B16 model, GEM model, immune cell profiling Oncotarget Medium 27341128
2016 MDA-9/Syntenin NMR-guided fragment-based drug design identified PDZ1i (113B7), which inhibits MDA-9/Syntenin binding to EGFRvIII; both genetic knockdown (shmda-9) and PDZ1i treatment reduced post-radiation invasion gains, FAK and EGFRvIII signaling, and MMP-2/MMP-9 secretion in GBM cells, with PDZ1i passing the blood-brain barrier and prolonging survival in vivo. NMR-guided fragment-based drug design, shRNA knockdown, pharmacological inhibition (PDZ1i), Co-IP of MDA-9–EGFRvIII, invasion assay, in vivo orthotopic GBM model Proceedings of the National Academy of Sciences of the United States of America High 28011764
2018 MDA-9/Syntenin maintains protective autophagy in glioma stem cells (GSCs) under anoikis conditions through FAK- and PKC-mediated phosphorylation of BCL2 and suppression of excessive autophagy markers (ATG5, LAMP1, LC3B) via EGFR signaling; loss of MDA-9 deregulates this mechanism, causing autophagic cell death. Gain-of-function/loss-of-function genetics (siRNA, shRNA), western blot for p-BCL2/p-EGFR/ATG5/LAMP1/LC3B, FAK/PKC inhibitors, anoikis assays in GSC sphere cultures Proceedings of the National Academy of Sciences of the United States of America Medium 29760085
2018 MDA-9/Syntenin physically interacts with IGF-1R upon IGFBP2 stimulation, regulating downstream STAT3 phosphorylation, which enhances MMP2/MMP9 expression and prostate cancer invasion. Co-IP (MDA-9–IGF1R), STAT3 phosphorylation assays, CRISPR/Cas9 KO, loss-of-function/gain-of-function, in vitro invasion assays Cancer research High 29572229
2018 MDA-9/Syntenin upregulates PD-L1 expression by inducing STAT3 Tyr705 phosphorylation, leading to CD8+ T cell apoptosis in vitro and in vivo and immune evasion in triple-negative breast cancer. Western blot, flow cytometry, STAT3 inhibition, in vivo 4T1 tumor model with syntenin KD/overexpression Breast cancer research and treatment Medium 29845474
2019 In glioma stem cells (GSCs), MDA-9 regulates stemness genes (Nanog, Oct4, Sox2) through STAT3 activation and controls GSC survival via the NOTCH1 pathway through phospho-Src and DLL1; activated NOTCH1 regulates C-Myc through RBPJK. Knockdown of MDA-9 simultaneously disrupts NOTCH1/C-Myc and p-STAT3/Nanog pathways, causing loss of stemness and apoptosis. siRNA/shRNA knockdown, pathway inhibitors, western blot for NOTCH1 cleavage/STAT3/Nanog/Oct4/Sox2, GSC sphere assays Oncotarget Medium 27472461
2019 In prostate cancer stem cells (PCSCs), MDA-9-mediated multiple drug resistance, stemness, and survival are regulated through STAT3 activation; activated STAT3 controls chemoresistance via protective autophagy and MDR1 surface expression; the STAT3 and c-Myc pathways are interconnected downstream of MDA-9. Genetic loss-of-function (siRNA/shRNA), pharmacological inhibitors, western blot, flow cytometry for MDR1, autophagy assays, chemosensitivity assays (docetaxel, trichostatin-A) Cancers Medium 31878027
2019 Blocking MDA-9/Syntenin by shRNA or the PDZ1i small-molecule inhibitor downregulates integrin α6 and β4, diminishes Src activity, suppresses Rho-Rac-Cdc42 activity, inhibits cofilin and MMPs, and reduces neuroblastoma migration and metastasis in vivo; overexpression of integrin α6/β4 rescues invasion, placing integrins upstream of Src in MDA-9-mediated migration. shRNA, siRNA, PDZ1i pharmacological inhibitor, integrin overexpression rescue, Rho/Rac/Cdc42 activity assays, in vivo metastasis model Oncogene Medium 31406249
2020 AURKA binds to SDCBP and phosphorylates it at Ser131 and Thr200, inhibiting ubiquitination-mediated SDCBP degradation; phosphorylated SDCBP activates the EGFR-PI3K-Akt signaling pathway by binding to EGFR and preventing EGFR internalization, promoting ESCC tumor growth. Co-IP (AURKA–SDCBP), phosphorylation site mapping (Ser131/Thr200), ubiquitination assays, EGFR internalization assay, in vitro kinase assay, xenograft model Oncogene High 32572158
2021 MDA-9/Syntenin PDZ1 domain pharmacological inhibition (PDZ1i) suppresses breast cancer metastasis and deregulates myeloid-derived suppressor cell (MDSC) differentiation via the STAT3/IL-1β pathway, concomitantly promoting cytotoxic T lymphocyte activation. PDZ1i treatment, genetic silencing, lung metastasis model, MDSC differentiation assays, T cell activation assays, IL-1β pathway analysis Proceedings of the National Academy of Sciences of the United States of America Medium 34016751
2023 SDCBP stabilizes YAP1 by directly interacting with the TAD domain of YAP1 (primarily via its PDZ1 domain) and inhibiting CK1δ/ε-mediated YAP1-S384/S387 phosphorylation, thereby suppressing β-TrCP-mediated ubiquitination and proteasomal degradation of YAP1, promoting PDAC proliferation and metastasis. Co-IP, pull-down assays, ubiquitination assays, domain mapping (PDZ1), phosphorylation site analysis, organoid models, KPC mouse model, PDX model Gut High 36828627
2023 SDCBP via its PDZ1 domain disassembles the SCFFBXO22-BACH1 ubiquitin-ligase complex, preventing BACH1 K48-linked polyubiquitination and proteasomal degradation; SDCBP knockdown degrades BACH1, downregulates BACH1-induced metastatic genes, and upregulates BACH1-repressed ETC genes (NDUFA4, COX6B2), increasing mitochondrial activity. Co-IP (SDCBP–BACH1–FBXO22 complex disassembly), ubiquitination assays (K48-linked), PDZ1 domain-specific knockdown constructs, gene expression analysis, mitochondrial activity assays, in vivo TNBC tumor model The EMBO journal High 40263598
2023 IVMT-Rx-3 (PDZ1i joined to PDZ2-binding peptide TNYYFV via PEG linker) simultaneously blocks both PDZ domains of MDA-9/Syntenin, inhibiting its interaction with Src, reducing NF-κB activation and MMP-2/MMP-9 expression, and repressing melanoma metastasis in vivo; combined with immune checkpoint inhibitor, antimetastatic effects are enhanced. NMR/fragment-based drug design, dual-PDZ inhibitor synthesis, Src Co-IP, NF-κB assay, MMP expression, in vivo melanoma metastasis model, combination with checkpoint inhibitor Molecular cancer therapeutics High 37721536
2023 Crystal structure of MDA-9/Syntenin PDZ1 domain in complex with small-molecule inhibitor PI1B was solved; mutagenesis of PDZ domain residues validated the protein-ligand interaction modes; PI1A and PI2A (PDZ1/PDZ2 inhibitors) blocked natural substrate binding (fluorescence polarization) and suppressed MDA-MB-231 breast cancer cell migration. X-ray crystallography (PDZ1–PI1B complex), NMR (transferred paramagnetic relaxation enhancement), site-directed mutagenesis, competitive fluorescence polarization, cell migration assay International journal of molecular sciences High 36834839
2023 In the bone metastasis niche, tumor cell-derived PDGF-AA induces CXCL5 expression in bone marrow-derived mesenchymal stromal cells (BM-MSCs) by suppressing MDA-9-dependent YAP/MST signaling; CXCL5 drives tumor cell proliferation and immune suppression. MDA-9 knockout tumor cells express less PDGF-AA and do not develop bone metastases. MDA-9 knockout tumor cells, conditioned media experiments, signaling assays (YAP/MST), in vivo bone metastasis models Proceedings of the National Academy of Sciences of the United States of America Medium 37922327
2014 MDA-9/Syntenin is dramatically upregulated by rFVIIa/FX combination in melanoma cells and physically interacts with c-Src through its PDZ binding motif following TF·FVIIa·Xa stimulation; this signaling involves PAR-1/c-Src/Rho GTPases Rac1 and Cdc42/JNK axis, activating paxillin, NF-κB, and MMP-2, and is required for TF·FVIIa·Xa-induced migration, invasion, and metastasis. Co-IP (MDA-9–c-Src), PDZ motif mutants, Rho GTPase activity assays, siRNA knockdown, invasion/migration assays, in vivo metastasis model The Journal of biological chemistry Medium 25505176
2013 In glioblastoma cells, MDA-9/Syntenin overexpression increases activation of c-Src, p38 MAPK, and NF-κB, leading to elevated MMP-2 expression and IL-8 secretion; knockdown inhibits invasion, migration, and anchorage-independent growth and reduces tumor size and invasion in orthotopic xenografts. Gain-of-function/loss-of-function (overexpression/shRNA), western blot signaling analysis, Matrigel invasion, soft agar, orthotopic xenograft Neuro-oncology Medium 24305713
2012 MDA-9/Syntenin promotes brain glioma cell migration by activating FAK-JNK and FAK-AKT signaling downstream of fibronectin adhesion; phosphorylation of FAK at Tyr397, Tyr576, and Tyr925 (but not Tyr861) is increased, and inhibition of JNK (SP600125) or PI3K (LY294002) decreases migration. Stable overexpression in glioma cells, wound-healing migration assay, western blot phosphorylation mapping, specific kinase inhibitors Asian Pacific journal of cancer prevention Low 22938480
2016 MDA-9/Syntenin interacts with the PDZ1 domain binding partner SPRR1B to disrupt differentiation signaling, and co-localizes with VEGFR1 to alter angiogenesis in HNSCC; silencing MDA-9 induced squamous differentiation and reduced VEGFR1 expression in vitro and in vivo. PDZ1 interaction mapping (SPRR1B), VEGFR1 co-localization (immunofluorescence), siRNA knockdown, in vitro differentiation/angiogenesis assays, in vivo tumor model Oncoscience Low 25593999
2012 MDA-9/Syntenin inhibition in uveal melanoma cells suppresses FAK, AKT, and Src activation and reduces HGF-triggered Matrigel invasion and wound-healing migration; overexpression has opposite effects, placing MDA-9 upstream of FAK/AKT/Src in uveal melanoma. siRNA knockdown, overexpression, Matrigel invasion, wound-healing assay, western blot for FAK/AKT/Src phosphorylation PloS one Low 22267972
2017 Wild-type SDCBP interacts with c-Src (Co-IP confirmed) and promotes phosphorylation of c-Src at Tyr419; this interaction requires the PDZ domain (SDCBP lacking the PDZ domain has no effect on c-Src phosphorylation); dasatinib blocks this phosphorylation and SDCBP-induced cell cycle (G1/S) progression. Co-immunoprecipitation, PDZ-domain deletion constructs, dasatinib pharmacological inhibition, cell cycle analysis, xenograft model PloS one Medium 28141839
2025 SDCBP knockdown inhibited HNSCC cancer stem cell markers, sensitized cells to cisplatin, and reduced Src activation (identified as the main downstream target of SDCBP), with reduced tumor growth and metastasis in vivo. SDCBP siRNA/shRNA depletion, Src activation assay, in vitro cisplatin sensitivity, in vivo xenograft model Cancers Low 34638436
2025 SDCBP promotes gastric cancer EMT via the ERK signaling pathway; knockdown of SDCBP or ERK signaling inhibition delayed cancer progression in xenograft experiments; SDCBP-knockdown in cancer cells also inhibited M2 polarization, reduced chemotaxis, and enhanced phagocytosis of co-cultured macrophages. SDCBP siRNA knockdown, ERK inhibitor, co-culture macrophage assays, xenograft model, western blot Molecular carcinogenesis Low 40256939
2025 SDCBP inhibition by IVMT-Rx-4 (improved PDZ1i derivative) suppresses PDGF-AA secretion from tumor cells and inhibits downstream signaling in BM-MSCs, blocking prostate cancer bone metastasis; combination with docetaxel enhanced survival in bone metastasis animal models. Small molecule (IVMT-Rx-4) pharmacological inhibition, PDGF-AA measurement, BM-MSC signaling assays, in vivo bone metastasis model, combination treatment Pharmacological research Medium 41865851

Source papers

Stage 0 corpus · 77 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2018 MDA-9/Syntenin regulates protective autophagy in anoikis-resistant glioma stem cells. Proceedings of the National Academy of Sciences of the United States of America 110 29760085
2005 mda-9/Syntenin: a positive regulator of melanoma metastasis. Cancer research 98 16322237
2008 mda-9/Syntenin promotes metastasis in human melanoma cells by activating c-Src. Proceedings of the National Academy of Sciences of the United States of America 96 18832467
2016 Inhibition of radiation-induced glioblastoma invasion by genetic and pharmacological targeting of MDA-9/Syntenin. Proceedings of the National Academy of Sciences of the United States of America 85 28011764
1998 Melanoma differentiation associated gene-9, mda-9, is a human gamma interferon responsive gene. Gene 80 9511750
2012 MDA-9/syntenin and IGFBP-2 promote angiogenesis in human melanoma. Cancer research 79 23233738
2007 RETRACTED: mda-9/Syntenin regulates the metastatic phenotype in human melanoma cells by activating nuclear factor-kappaB. Cancer research 77 17308124
2010 Activation of the integrin effector kinase focal adhesion kinase in cancer cells is regulated by crosstalk between protein kinase Calpha and the PDZ adapter protein mda-9/Syntenin. Cancer research 74 20145126
2012 Mda-9/syntenin is expressed in uveal melanoma and correlates with metastatic progression. PloS one 72 22267972
2010 Src kinase activation is mandatory for MDA-9/syntenin-mediated activation of nuclear factor-kappaB. Oncogene 63 20228839
2012 MDA-9/syntenin: a positive gatekeeper of melanoma metastasis. Frontiers in bioscience (Landmark edition) 62 22201728
2008 mda-9/Syntenin: more than just a simple adapter protein when it comes to cancer metastasis. Cancer research 62 18451132
2012 Raf kinase inhibitor RKIP inhibits MDA-9/syntenin-mediated metastasis in melanoma. Cancer research 56 23066033
2013 Novel role of MDA-9/syntenin in regulating urothelial cell proliferation by modulating EGFR signaling. Clinical cancer research : an official journal of the American Association for Cancer Research 55 23873690
2013 MDA-9/syntenin is a key regulator of glioma pathogenesis. Neuro-oncology 54 24305713
2004 mda-9/syntenin: recent insights into a novel cell signaling and metastasis-associated gene. Pharmacology & therapeutics 53 15518882
2014 Targeting tumor invasion: the roles of MDA-9/Syntenin. Expert opinion on therapeutic targets 50 25219541
2018 The MDA-9/Syntenin/IGF1R/STAT3 Axis Directs Prostate Cancer Invasion. Cancer research 46 29572229
2013 Syndecan binding protein (SDCBP) is overexpressed in estrogen receptor negative breast cancers, and is a potential promoter for tumor proliferation. PloS one 46 23533663
2016 miR-216b suppresses breast cancer growth and metastasis by targeting SDCBP. Biochemical and biophysical research communications 45 27720715
2020 MDA-9/Syntenin (SDCBP): Novel gene and therapeutic target for cancer metastasis. Pharmacological research 44 32061839
2016 MDA-9/Syntenin (SDCBP) modulates small GTPases RhoA and Cdc42 via transforming growth factor β1 to enhance epithelial-mesenchymal transition in breast cancer. Oncotarget 44 27863394
2014 MDA-9 and GRP78 as potential diagnostic biomarkers for early detection of melanoma metastasis. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 44 25480418
2020 The MGF360-16R ORF of African Swine Fever Virus Strain Georgia Encodes for a Nonessential Gene That Interacts with Host Proteins SERTAD3 and SDCBP. Viruses 41 31947814
2020 SDCBP/MDA-9/syntenin phosphorylation by AURKA promotes esophageal squamous cell carcinoma progression through the EGFR-PI3K-Akt signaling pathway. Oncogene 40 32572158
2023 SDCBP promotes pancreatic cancer progression by preventing YAP1 from β-TrCP-mediated proteasomal degradation. Gut 37 36828627
2020 MDA-9/Syntenin/SDCBP: new insights into a unique multifunctional scaffold protein. Cancer metastasis reviews 37 32410111
2018 Syntenin1/MDA-9 (SDCBP) induces immune evasion in triple-negative breast cancer by upregulating PD-L1. Breast cancer research and treatment 37 29845474
2018 Regulation of protective autophagy in anoikis-resistant glioma stem cells by SDCBP/MDA-9/Syntenin. Autophagy 35 30118375
2019 MDA-9/Syntenin (SDCBP) Is a Critical Regulator of Chemoresistance, Survival and Stemness in Prostate Cancer Stem Cells. Cancers 34 31878027
2017 Dasatinib inhibits c-src phosphorylation and prevents the proliferation of Triple-Negative Breast Cancer (TNBC) cells which overexpress Syndecan-Binding Protein (SDCBP). PloS one 33 28141839
2019 Regulation of neuroblastoma migration, invasion, and in vivo metastasis by genetic and pharmacological manipulation of MDA-9/Syntenin. Oncogene 31 31406249
2021 Pharmacological inhibition of MDA-9/Syntenin blocks breast cancer metastasis through suppression of IL-1β. Proceedings of the National Academy of Sciences of the United States of America 30 34016751
2016 ACTB, CDKN1B, GAPDH, GRB2, RHOA and SDCBP Were Identified as Reference Genes in Neuroendocrine Lung Cancer via the nCounter Technology. PloS one 30 27802291
2016 Knockout of MDA-9/Syntenin (SDCBP) expression in the microenvironment dampens tumor-supporting inflammation and inhibits melanoma metastasis. Oncotarget 29 27341128
2019 Suppression of Prostate Cancer Pathogenesis Using an MDA-9/Syntenin (SDCBP) PDZ1 Small-Molecule Inhibitor. Molecular cancer therapeutics 27 31345950
2018 MiRNA-139-3p inhibits the proliferation, invasion, and migration of human glioma cells by targeting MDA-9/syntenin. Biochemical and biophysical research communications 26 30502089
2016 MDA-9/Syntenin-Slug transcriptional complex promote epithelial-mesenchymal transition and invasion/metastasis in lung adenocarcinoma. Oncotarget 25 26561205
2012 Mda-9/syntenin promotes human brain glioma migration through focal adhesion kinase (FAK)-JNK and FAK-AKT signaling. Asian Pacific journal of cancer prevention : APJCP 25 22938480
2011 mda-9/Syntenin protein positively regulates the activation of Akt protein by facilitating integrin-linked kinase adaptor function during adhesion to type I collagen. The Journal of biological chemistry 25 21828040
2016 Novel function of MDA-9/Syntenin (SDCBP) as a regulator of survival and stemness in glioma stem cells. Oncotarget 24 27472461
2015 Examination of Epigenetic and other Molecular Factors Associated with mda-9/Syntenin Dysregulation in Cancer Through Integrated Analyses of Public Genomic Datasets. Advances in cancer research 24 26093898
2022 PRKAR1A and SDCBP Serve as Potential Predictors of Heart Failure Following Acute Myocardial Infarction. Frontiers in immunology 23 35592331
2019 Repression of miR-135b-5p promotes metastasis of early-stage breast cancer by regulating downstream target SDCBP. Laboratory investigation; a journal of technical methods and pathology 23 31024042
2019 MDA-9/Syntenin: An emerging global molecular target regulating cancer invasion and metastasis. Advances in cancer research 23 31349898
2017 IL-6 increases SDCBP expression, cell proliferation, and cell invasion by activating JAK2/STAT3 in human glioma cells. American journal of translational research 23 29118922
2014 MDA-9/Syntenin regulates differentiation and angiogenesis programs in head and neck squamous cell carcinoma. Oncoscience 23 25593999
2015 MDA-9/Syntenin Control. Journal of cellular physiology 21 26291527
2021 Single-cell RNA sequencing identify SDCBP in ACE2-positive bronchial epithelial cells negatively correlates with COVID-19 severity. Journal of cellular and molecular medicine 20 34137173
2022 SDCBP-AS1 destabilizes β-catenin by regulating ubiquitination and SUMOylation of hnRNP K to suppress gastric tumorigenicity and metastasis. Cancer communications (London, England) 19 36209503
2011 MDA-9/syntenin interacts with ubiquitin via a novel ubiquitin-binding motif. Molecular and cellular biochemistry 19 21359963
2021 SDCBP Modulates Stemness and Chemoresistance in Head and Neck Squamous Cell Carcinoma through Src Activation. Cancers 15 34638436
2019 Rethinking Glioblastoma Therapy: MDA-9/Syntenin Targeted Small Molecule. ACS chemical neuroscience 15 30681320
2019 A PDZ Protein MDA-9/Syntenin: As a Target for Cancer Therapy. Computational and structural biotechnology journal 14 30766662
2018 MicroRNA-23a inhibits melanoma cell proliferation, migration, and invasion in mice through a negative feedback regulation of sdcbp and the MAPK/ERK signaling pathway. IUBMB life 13 30589231
2021 Downregulation of SDCBP inhibits cell proliferation and induces apoptosis by regulating PI3K/AKT/mTOR pathway in gastric carcinoma. Biotechnology and applied biochemistry 12 33432665
2012 Expression patterns of MDA-9/syntenin during development of the mouse embryo. Journal of molecular histology 12 23180153
2023 MDA-9/Syntenin in the tumor and microenvironment defines prostate cancer bone metastasis. Proceedings of the National Academy of Sciences of the United States of America 11 37922327
2023 Dual Targeting of the PDZ1 and PDZ2 Domains of MDA-9/Syntenin Inhibits Melanoma Metastasis. Molecular cancer therapeutics 9 37721536
2023 Inhibitors against Two PDZ Domains of MDA-9 Suppressed Migration of Breast Cancer Cells. International journal of molecular sciences 8 36834839
2018 Potential Therapeutic Applications of MDA-9/Syntenin-NF-κB-RKIP Loop in Human Liver Carcinoma. Current molecular medicine 8 30608040
2024 SDCBP modulates tumor microenvironment, tumor progression and anti-PD1 efficacy in colorectal cancer. Cancer gene therapy 7 38555398
2014 MDA-9/syntenin is essential for factor VIIa-induced signaling, migration, and metastasis in melanoma cells. The Journal of biological chemistry 7 25505176
2025 Identification of multicohort-based predictive signature for NMIBC recurrence reveals SDCBP as a novel oncogene in bladder cancer. Annals of medicine 5 39873429
2024 Dexrazoxane inhibits the growth of esophageal squamous cell carcinoma by attenuating SDCBP/MDA-9/syntenin-mediated EGFR-PI3K-Akt pathway activation. Scientific reports 5 38649770
2024 Knockdown of SDCBP induces autophagy to promote cardiomyocyte growth and angiogenesis in hypoxia/reoxygenation model. Mutation research 5 39486220
2025 MDA-9/Syntenin as a therapeutic cancer metastasis target: current molecular and preclinical understanding. Expert opinion on therapeutic targets 4 40056146
2024 Design and Synthesis of Small Molecule Probes of MDA-9/Syntenin. Biomolecules 4 39456220
2023 Recurrent 8q11-13 Aberrations Leading to PLAG1 Rearrangements, Including Novel Chimeras HNRNPA2B1::PLAG1 and SDCBP::PLAG1, in Lipomatous Tumors. Cancer genomics & proteomics 3 36870688
2025 SDCBP Orchestrated Gastric Cancer Aggression Through Epithelial- Mesenchymal Transition and Macrophages M2 Polarization. Molecular carcinogenesis 1 40256939
2025 SDCBP/Syntenin-1 stabilizes BACH1 by disassembling the SCFFBXO22-BACH1 complex in triple-negative breast cancer. The EMBO journal 1 40263598
2012 Molecular studies on chicken melanoma differentiation associated gene-9 (mda-9). Allergologia et immunopathologia 1 23245759
2026 MDA-9/Syntenin small molecule inhibitor IVMT-Rx-4 blocks prostate cancer bone metastasis. Pharmacological research 0 41865851
2025 WISP3 upregulates SDCBP expression to promote the progression of non-small cell lung cancer via the TGF-β signaling pathway. Biochemical pharmacology 0 40571215
2025 Anoikis-related biomarkers PARP1 and SDCBP as diagnostic and therapeutic targets for asthma. Scientific reports 0 40634444
2025 MDA-9/Syntenin promotes glioma cell proliferation and invasion via exosome-mediated activation of the PI3K-AKT signaling pathway. Biochemical and biophysical research communications 0 41033115
2025 Decoding SDCBP's role in tumor progression and immune cells infiltration: from databases to macrophage validation. Discover oncology 0 41423524

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