Affinage

SASH1

SAM and SH3 domain-containing protein 1 · UniProt O94885

Length
1247 aa
Mass
136.7 kDa
Annotated
2026-06-10
67 papers in source corpus 29 papers cited in narrative 29 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SASH1 is a multidomain SH3/SAM-containing scaffold/adaptor protein that nucleates signaling complexes at the actin cytoskeleton, cell-cell junctions, and inflammatory and growth-control pathways, broadly acting as a tumor-suppressive organizer of adhesion and migration (PMID:21820526, PMID:23776175, PMID:30480076). In epithelial cells it co-distributes with the actin cytoskeleton and binds cortactin to promote filamentous actin and cell-matrix adhesion while restraining migration, and it localizes to adherens junctions where its loss precipitates a mesenchymal transition (PMID:21820526, PMID:32586229). As a TLR4 scaffold in endothelial cells, SASH1 independently binds TRAF6, TAK1, and IKKα/β, promotes TRAF6/TAK1 ubiquitination, and drives NF-κB/JNK/p38-dependent inflammatory signaling; downstream it engages β-arrestin 1 to activate Akt and eNOS, and Sash1-null mice die perinatally from defective nitric-oxide-dependent alveolar epithelial maturation (PMID:23776175, PMID:31067462). SASH1 suppresses tumor cell invasion through several convergent routes: it binds the oncoprotein CRKL to inhibit SRC kinase and block EMT and metastasis (PMID:30480076), and it operates within the Hippo pathway as a LATS1/LATS2 substrate (phosphorylated at S407) that restrains YAP and the downstream YAP-ARHGAP42-actin invasion axis (PMID:32523092, PMID:38657867). During UVC-induced apoptosis SASH1 is cleaved by caspase-3, and its C-terminal fragment translocates to the nucleus and chromatin to drive NF-κB-dependent apoptosis (PMID:27831555). Through its SAM1 domain SASH1 engages additional partners—Eph receptors (notably EphA8, by a structurally defined SAM-SAM interaction that modulates kinase activity), Caskin1/2 (disrupting their SAM homopolymer), and tankyrase-2 (TNKS2, required for melanocyte stem-cell maintenance)—establishing the SAM domain as a key interaction hub (PMID:36341956, PMID:37619706, PMID:39688081, PMID:38848986). SASH1 mutations cause dyschromatosis/dyschromatosis universalis hereditaria with pathological hyperpigmentation through altered melanocyte migration and pigmentation signaling (PMID:23333244, PMID:32174800). In cancer, SASH1 is epigenetically silenced via HMGB1-directed CpG methylation and an HMGB1/SET/HAT1 histone-deacetylation complex at the SASH1 locus (PMID:31138780, PMID:37794134).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 2003 Low

    Established SASH1 as a candidate signaling adaptor by identifying its SH3 and SAM domains, framing all subsequent mechanistic work as scaffold biology.

    Evidence In silico domain analysis with EST/genomic comparison and Northern blot

    PMID:12771949

    Open questions at the time
    • Domain inference only, no functional partner or activity demonstrated
    • No subcellular localization established
  2. 2011 Medium

    Connected SASH1 to the actin cytoskeleton, answering what cellular structure it acts on by showing cortactin binding and control of actin-driven adhesion and migration.

    Evidence Immunofluorescence co-localization, domain mapping, F-actin staining, adhesion/migration assays with siRNA in epithelial cells

    PMID:21820526

    Open questions at the time
    • Cortactin interaction not validated reciprocally or structurally
    • Molecular basis of adhesion increase unresolved
  3. 2013 High

    Defined SASH1 as a TLR4 inflammatory scaffold, resolving how it links receptor engagement to NF-κB/MAPK output via direct binding to multiple pathway kinases.

    Evidence Reciprocal Co-IP of TRAF6/TAK1/IKKα/β, ubiquitination assays, and pathway/cytokine readouts in LPS-stimulated endothelial cells

    PMID:23776175

    Open questions at the time
    • Stoichiometry and order of complex assembly not defined
    • Which domain mediates each kinase contact unknown
  4. 2013 Medium

    Linked SASH1 mutations to a disease mechanism by showing mutant SASH1 increases melanocyte migration through altered IQGAP1/Gαs binding and E-cadherin loss.

    Evidence Patient mutation analysis, Co-IP (IQGAP1, Gαs), migration assays, E-cadherin Western blot

    PMID:23333244

    Open questions at the time
    • Direct vs indirect binding of IQGAP1/Gαs unresolved
    • How mutation alters binding mechanistically not shown
  5. 2016 High

    Revealed a caspase-regulated nuclear function, showing caspase-3 cleavage generates a C-terminal fragment that drives NF-κB-dependent apoptosis.

    Evidence Caspase cleavage assays, cleavage-site mutagenesis, subcellular fractionation, NF-κB inhibitor (DHMEQ) after UVC

    PMID:27831555

    Open questions at the time
    • Nuclear targets of the cleaved fragment not identified
    • Mechanism of NF-κB activation by the fragment undefined
  6. 2016 Medium

    Placed SASH1 upstream of multiple oncogenic kinase/morphogen pathways (Shh-Gli1, PI3K/Akt, FAK) as a suppressor of proliferation and invasion.

    Evidence Overexpression with pharmacological agonist rescue, Western blot pathway readouts, xenograft and Transwell assays across hepatocarcinoma, gastric and cervical cancer models

    PMID:26935246 PMID:27178818 PMID:28600143

    Open questions at the time
    • Pathway placements rely on Western blot/epistasis without direct binding for several
    • Direct molecular target within each pathway unidentified
  7. 2017 Medium

    Showed SASH1 governs epithelial lumenogenesis through a DLK1-NOTCH1 axis downstream of CEACAM1.

    Evidence RNAi, 3D lumen formation assay, gene array, DLK1 RNAi and γ-secretase epistasis

    PMID:28823832

    Open questions at the time
    • How SASH1 controls DLK1 expression unknown
    • No physical interaction defined in this axis
  8. 2018 High

    Identified CRKL as a direct partner whose SRC activation SASH1 inhibits, providing a defined molecular route by which SASH1 suppresses EMT and metastasis.

    Evidence Y2H, Co-IP/MS, domain mapping, dynamic mass redistribution, CRISPR knockout and in vivo metastasis with CRKL-dependent epistasis

    PMID:30480076

    Open questions at the time
    • How CRKL binding restrains SRC mechanistically not fully resolved
    • Structural basis of SASH1-CRKL contact undefined
  9. 2019 High

    Defined an essential developmental role: endothelial SASH1 acts through β-arrestin 1 to drive eNOS/NO signaling that non-autonomously matures alveolar epithelium.

    Evidence Global and endothelial-conditional Sash1 knockout mice, Co-IP (β-arrestin 1), eNOS/Akt/cGMP assays, surfactant and histology

    PMID:31067462

    Open questions at the time
    • Relationship between β-arrestin1 and TLR4 kinase complex unresolved
    • Direct vs indirect eNOS activation mechanism not detailed
  10. 2019 Medium

    Established epigenetic silencing of SASH1 via HMGB1-directed CpG methylation, with downstream integrin β8 control of adhesion/migration.

    Evidence Methylation assay, ChIP (HMGB1 at SASH1 CpG islands), HMGB1 overexpression, integrin β8 Western blot in astrocytes

    PMID:31138780

    Open questions at the time
    • Methyltransferase recruited by HMGB1 not identified
    • Direct vs indirect integrin β8 regulation unclear
  11. 2020 High

    Embedded SASH1 in Hippo signaling as both a LATS substrate (S407) and regulator of YAP, defining the YAP-ARHGAP42-actin axis driving invasion.

    Evidence Phospho-Western, S407A mutagenesis with rescue failure, YAP/ARHGAP42 epistasis, CAM and xenograft models in TNBC

    PMID:32523092

    Open questions at the time
    • How SASH1 reciprocally promotes LATS1 activity unknown
    • Functional consequence of S407 phosphorylation on SASH1 structure undefined
  12. 2020 Medium

    Reinforced SASH1's adhesion-maintaining role and characterized melanocyte-pigmentation mechanisms (Mitf, THBS1/TGF-β1) underlying its mutation phenotypes.

    Evidence Confocal localization at adherens junctions with RNAi (epithelial cells); Y551D knock-in mice with Mitf IHC; patient-mutation THBS1/TGF-β1 migration assays

    PMID:32174800 PMID:32582980 PMID:32586229

    Open questions at the time
    • Whether SASH1 directly binds Mitf complex unproven
    • Mechanism linking SASH1 to THBS1 transcription unresolved
  13. 2022 High

    Provided the first structural insight into the SAM1 domain, showing it is a predominantly disordered monomer distinct from related SAM domains, with a mapped oligomerization region.

    Evidence NMR, SEC-MALS, SE-HPLC and D663A/T664K mutagenesis

    PMID:36341956

    Open questions at the time
    • Functional role of monomeric vs oligomeric state in cells unknown
    • Link between oligomerization and partner binding untested
  14. 2022 Medium

    Extended SASH1's TRAF6-ubiquitination scaffold function to stabilize EZH2 and identified roles in glial differentiation maintenance.

    Evidence Co-IP/ubiquitination assays with EZH2 rescue in hemangioma endothelial cells; siRNA in astrocytes with ELISA/Western and co-culture axonal assays

    PMID:35772492 PMID:36286186

    Open questions at the time
    • How SASH1 promotes TRAF6 ubiquitination toward EZH2 stability unclear
    • Direct vs indirect control of glial differentiation factors undefined
  15. 2023 High

    Established the SAM1 domain as a versatile interaction hub by defining structurally resolved interactions with Eph receptors (EphA8) and Caskin1/2.

    Evidence Crystal structure of EphA8-SASH1, Co-IP, kinase assays, cancer mutation analysis; Y2H/ITC/GST pulldown with AlphaFold2 modeling and polymer-disruption assays for Caskin

    PMID:37619706 PMID:39688081

    Open questions at the time
    • Cellular consequence of SASH1 on EphA8 signaling output beyond kinase assay limited
    • Physiological context of SASH1-Caskin interaction not established
  16. 2023 Medium

    Identified TNKS2 as a SASH1 partner required for melanocyte stem-cell maintenance, with a disease variant (S519N) in the tankyrase-binding motif impairing this function.

    Evidence Y2H, binding kinetics/affinity assays, stem-cell functional assays (preprint then peer-reviewed) with S519N variant analysis

    PMID:37808724 PMID:38848986

    Open questions at the time
    • Downstream consequence of TNKS2 binding on SASH1 fate unknown
    • Whether SASH1 is a tankyrase substrate untested
  17. 2023 Medium

    Demonstrated functional conservation of SASH1 in glial migration during brain development using zebrafish with human mRNA rescue.

    Evidence sash1a morpholino/CRISPR knockdown, transgenic reporter lines, human SASH1 mRNA rescue

    PMID:37741309

    Open questions at the time
    • Molecular pathway driving glial migration phenotype unidentified
    • Cell-autonomous vs non-autonomous requirement unresolved
  18. 2024 Medium

    Extended the Hippo connection by identifying a MAP4K4-LATS2-SASH1-YAP1 cascade, with LATS2 directly phosphorylating SASH1.

    Evidence LATS2 kinase assay on SASH1, overexpression/siRNA epistasis, nuclear fractionation, tumor models in luminal breast cancer

    PMID:38657867

    Open questions at the time
    • Phosphosite(s) targeted by LATS2 not mapped
    • How SASH1 transmits to YAP1 within the cascade unclear
  19. 2026 Medium

    Revealed a metabolic role in which SASH1 sequesters PKM2 in astrocytes to restrain glycolysis, with a disrupting peptide promoting TBI wound healing.

    Evidence Co-IP (SASH1-PKM2), nuclear fractionation, metabolic assays, peptide disruption in a mouse TBI model

    PMID:41690666

    Open questions at the time
    • Structural basis of SASH1-PKM2 interaction undefined
    • Whether this mechanism operates in other cell types unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How SASH1's many partner interactions are coordinated by its SH3 and SAM domains into context-specific complexes, and which domain configurations switch it between adhesion, inflammatory, Hippo, and metabolic functions, remains unresolved.
  • No integrated structural model of full-length SASH1 with multiple partners
  • Determinants of cell-type-specific partner selection unknown
  • Post-translational regulation governing function-switching incompletely mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 4 GO:0098772 molecular function regulator activity 4 GO:0008092 cytoskeletal protein binding 2
Localization
GO:0005634 nucleus 3 GO:0005829 cytosol 2 GO:0005856 cytoskeleton 2 GO:0005886 plasma membrane 2
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-1266738 Developmental Biology 2 R-HSA-1474244 Extracellular matrix organization 2 R-HSA-168256 Immune System 2 R-HSA-5357801 Programmed Cell Death 1
Partners
ARRB1CASKIN1CRKLEPHA8LATS1PKM2TNKS2TRAF6
Complex memberships
TLR4-TRAF6-TAK1-IKK scaffold complex

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 SASH1 encodes a member of the SH3/SAM adapter molecule family, with protein domain analysis revealing SH3 and SAM domains, suggesting a role in signaling pathways. Two transcripts (~4.4 and ~7.5 kb) were identified. In silico domain analysis, EST/genomic sequence comparison, Northern blot Oncogene Low 12771949
2011 SASH1 localizes to the nucleus, cytoplasm, lamellipodia, and membrane ruffles in epithelial cells, where it co-distributes with the actin cytoskeleton. SASH1 interacts with cortactin (an actin polymerization regulator). Overexpression increases filamentous actin content and cell protrusions; this activity maps to the central conserved domain. SASH1 overexpression inhibits cell migration and increases adhesion to fibronectin and laminin, while knockdown reduces cell-matrix adhesion. Immunofluorescence/co-localization, structural domain mutants, F-actin staining, migration assays, adhesion assays, siRNA knockdown The international journal of biochemistry & cell biology Medium 21820526
2013 SASH1 acts as a scaffold protein in TLR4 signaling in endothelial cells, independently binding TRAF6, TAK1, IκB kinase α, and IκB kinase β. This interaction fosters ubiquitination of TRAF6 and TAK1 and promotes LPS-induced NF-κB, JNK, and p38 activation, increasing proinflammatory cytokine production and LPS-induced endothelial migration. Co-immunoprecipitation, ubiquitination assays, LPS stimulation, NF-κB/JNK/p38 pathway assays, cytokine measurements, migration assays Journal of immunology High 23776175
2013 SASH1 mutations associated with dyschromatosis cause increased melanocyte migration. Mutated SASH1 shows intensified binding with IQGAP1 and Gαs, and induces uniform loss of E-Cadherin in A375 cells, suggesting SASH1 regulates IQGAP1-E-Cadherin signaling and acts as a scaffold linking GPCR/calmodulin signaling to melanocyte invasion. Patient mutation identification, functional cell migration assays, co-immunoprecipitation (IQGAP1, Gαs binding), Western blot (E-Cadherin) Cellular signalling Medium 23333244
2016 SASH1 is cleaved by caspase-3 following UVC-induced apoptosis. The C-terminal cleavage fragment (aa 231–1247) translocates from the cytoplasm to the nucleus and associates with chromatin. Overexpression of wild-type or cleaved SASH1 increases apoptosis; mutation of the cleavage site inhibits nuclear translocation and prevents apoptosis initiation. SASH1 cleavage is required for efficient nuclear translocation of NF-κB, and the effect of SASH1 on apoptosis is NF-κB-dependent (demonstrated by DHMEQ inhibitor). Caspase cleavage assays, UVC treatment, subcellular fractionation/immunofluorescence (nuclear translocation), site-directed mutagenesis of cleavage site, apoptosis assays, NF-κB inhibitor (DHMEQ) Cell death & disease High 27831555
2016 SASH1 is regulated by a p53/POMC/α-MSH/Gαs/SASH1 cascade mediating melanogenesis. A novel p53/POMC/Gαs/SASH1 autoregulatory positive feedback loop is activated by SASH1 mutations to induce pathological hyperpigmentation. SASH1 is physiologically induced by p53 upon UV stimulation, and SASH1 and p53 are reciprocally induced. Reporter assays, Western blot, UV stimulation experiments, patient mutation analysis, pathway activation assays Journal of cellular and molecular medicine Medium 27885802
2017 SASH1 overexpression suppresses Shh and downstream Gli1, Smo, Ptc signaling in hepatocarcinoma cells, inhibiting proliferation and invasion. This effect was reversed by Shh pathway agonist purmorphamine or PI3K/Akt agonists (740Y-P, PDGF), placing SASH1 upstream of Shh-Gli1 and PI3K/Akt pathways to inhibit invasion and metastasis in vivo and in vitro. Western blot, qRT-PCR, Transwell assay, pharmacological agonist rescue (purmorphamine, 740Y-P, PDGF), orthotopic xenograft mouse model The international journal of biochemistry & cell biology Medium 28600143
2017 SASH1 is critical for lumen formation in a 3D breast cancer model. SASH1 RNAi inhibits lumen formation downstream of CEACAM1. SASH1 acts through DLK1 (a NOTCH1 inhibitor) to regulate NOTCH1 signaling; SASH1 RNAi down-regulates DLK1, and DLK1 RNAi also inhibits lumen formation. NOTCH1 and its target genes HES1 and HEY1 are up-regulated by SASH1 RNAi and down-regulated by DLK1 RNAi, placing SASH1 upstream of DLK1-NOTCH1 in lumenogenesis. RNAi knockdown, 3D culture lumen formation assay, gene array, epistasis (DLK1 RNAi, γ-secretase inhibitor) Experimental cell research Medium 28823832
2018 SASH1 interacts with the oncoprotein CRKL (identified by yeast 2-hybrid and co-immunoprecipitation/mass spectrometry, confirmed by domain mapping, site-directed mutagenesis, and dynamic mass redistribution assays). SASH1 inhibits CRKL-mediated activation of SRC kinase, which is required for EMT. SASH1-deficient colon cancer cells undergo EMT and form more metastases in vivo; these effects depend entirely on CRKL. Yeast 2-hybrid, co-immunoprecipitation/mass spectrometry, domain mapping, site-directed mutagenesis, dynamic mass redistribution assay, CRISPR/Cas9 knockout, RNAi, EMT assays, orthotopic mouse metastasis model Cellular and molecular gastroenterology and hepatology High 30480076
2019 Endothelial Sash1 interacts with β-arrestin 1 downstream of the TLR4 pathway to activate Akt and endothelial nitric oxide synthase (eNOS) in microvascular endothelial cells. Nitric oxide generated downstream of Sash1 in endothelial cells affects alveolar epithelial cells in a cGMP-dependent manner, inducing maturation of alveolar type 1 and 2 cells and promoting pulmonary surfactant production. Sash1-/- mice die perinatally from respiratory distress due to delayed alveolar epithelial maturation. Sash1 knockout mouse generation, endothelial-restricted conditional knockout, co-immunoprecipitation (β-arrestin 1), eNOS/Akt activity assays, cGMP pathway assays, surfactant protein measurement, histology Cell reports High 31067462
2019 HMGB1 contributes to methylation of SASH1 gene CpG islands (demonstrated by ChIP assay showing HMGB1 binding to SASH1 CpG islands); HMGB1 overexpression in astrocytes increases SASH1 methylation level. Reduced SASH1 expression in turn decreases integrin β8 expression, reducing cell adhesion and promoting migration. Methylation assay, ChIP assay (HMGB1 binding to SASH1 CpG islands), HMGB1 overexpression, integrin β8 Western blot, adhesion/invasion assays Cell death & disease Medium 31138780
2020 SASH1 knockdown in TNBC cells downregulates phosphorylation of LATS1 and its effector YAP, leading to YAP accumulation and upregulation of CYR61. SASH1-induced YAP regulation is LATS1-dependent; in reverse, LATS1 phosphorylates SASH1 at S407. The phosphorylation-deficient SASH1 S407A mutant fails to rescue altered YAP signaling. SASH1 depletion upregulates ARHGAP42 via YAP-TEAD, and the YAP-ARHGAP42-actin axis drives SASH1-regulated TNBC cell invasion. siRNA knockdown, SASH1 overexpression, phospho-Western blot (LATS1, YAP), CYR61 assay, YAP pharmacological inhibitor and siRNA epistasis, S407A mutagenesis, ARHGAP42 knockdown, chicken CAM and mouse xenograft models Oncogene High 32523092
2020 SASH1 co-localizes with linear adherens junctions (AJs) and circumferential actin bundles in normal epithelial cells. SASH1 depletion by RNAi in IAR-20 cells destroys stable linear AJs and induces acquisition of mesenchymal phenotype, demonstrating SASH1's role in maintaining stable cell-cell adhesion. Immunofluorescence, confocal microscopy, RNAi knockdown, EMT assay Biochemistry. Biokhimiia Medium 32586229
2020 Mutated SASH1 (Y551D) knock-in mice show increased expression of Mitf (microphthalmia-associated transcription factor) in tail epithelium and increased Mitf-positive epithelial cells, recapitulating DUH hyperpigmentation. SASH1 may function as a scaffold to assemble a SASH1-Mitf molecular complex regulating Mitf expression in the nucleus. Heterozygous SASH1 knock-in mouse model (Y551D), immunohistochemistry, in vitro cell assays International journal of molecular medicine Medium 32582980
2020 SASH1 mutations (identified in DUH families) downregulate THBS1 (thrombospondin 1) expression and inactivate TGF-β1 signaling, promoting melanocyte migration and invasion. TGF-β1 expressed by melanocytes negatively regulates SASH1 protein expression, establishing a reciprocal regulatory relationship. Patient mutation identification, bioinformatics (THBS1 pathway), Transwell/wound-healing migration assays, Western blot (TGF-β1, SASH1), melanin content measurement International journal of biological sciences Medium 32174800
2022 The SAM1 domain of SASH1 exists primarily as a disordered monomer with a minor oligomer in solution, unlike the dimeric SAM domain of the related SASH3. NMR and SEC-MALS characterization revealed multiple timescale exchange regimes. D663A/T664K substitutions in SAM1 increased oligomerization, identifying a region important for oligomerization. SEC-MALS, HPLC, NMR (assignment, relaxation, exchange experiments), site-directed mutagenesis (D663A/T664K), SE-HPLC Journal of structural biology High 36341956
2022 SASH1 knockdown in hemangioma endothelial cells (HemECs) suppresses TRAF6 ubiquitination, leading to destabilization and reduced expression of EZH2. Co-immunoprecipitation confirmed regulation of TRAF6 and EZH2 ubiquitination by SASH1. EZH2 overexpression reversed the anti-proliferative and pro-apoptotic effects of SASH1 knockdown. Co-immunoprecipitation, ubiquitination assay, CCK-8/cell cycle/apoptosis assays, wound healing/Transwell assays, EZH2 overexpression rescue Experimental cell research Medium 35772492
2023 SASH1 is a novel binding partner of Eph receptors, interacting via SAM-SAM domain interactions. SASH1 selectively interacts with Eph receptors through its SAM1 domain, with highest affinity for EphA8. The crystal structure of the EphA8-SASH1 complex revealed specific intermolecular interactions. EphA8 and SASH1 co-localize and co-precipitate in mammalian cells. Cancer mutations (EphA8 R942H or G978D) impair this interaction. SAM-SAM interaction is critical for SASH1-mediated regulation of EphA8 kinase activity. Crystal structure determination, biochemical binding assays, co-immunoprecipitation, co-localization assays in mammalian cells, cancer mutation analysis, kinase activity assays Journal of molecular biology High 37619706
2023 HMGB1 forms a physical complex with SET and HAT1 in lung adenocarcinoma cells (HMGB1/SET/HAT1 complex), inhibiting H3K9 and H3K27 acetylation at the SASH1 locus, thereby suppressing SASH1 expression and facilitating glycolysis and metastasis. Co-immunoprecipitation (HMGB1/SET/HAT1 complex), ChIP (H3K9ace, H3K27ace), Western blot, in vitro and in vivo tumor models Oncogene Medium 37794134
2023 SASH1 interacts with Caskin1/2 via SAM-SAM domain interactions (SASH1 SAM1 domain). This interaction disrupts the Caskin1 tandem SAM homopolymer. Key residues at the end-helix/mid-loop interface mediate this interaction. Structural insights were provided by AlphaFold2-predicted models validated by mutagenesis. Yeast 2-hybrid screening, SEC, ITC, GST pull-down, co-immunoprecipitation, AlphaFold2 structural modeling, mutagenesis, sedimentation assay, TEM, immunofluorescence The FEBS journal High 39688081
2024 LATS2 phosphorylates SASH1, forming a MAP4K4-LATS2-SASH1-YAP1 cascade in luminal breast cancer. MAP4K4 negatively regulates LATS2, SASH1, and YAP1 expression and YAP1 phosphorylation. Combined MAP4K4 overexpression and SASH1 silencing promote YAP1 dephosphorylation, YAP1/TAZ nuclear translocation, and downstream transcriptional regulation. Overexpression and siRNA knockdown, phosphorylation assays (LATS2 kinase assay on SASH1), Western blot, nuclear fractionation, in vitro and in vivo tumor models The Journal of biological chemistry Medium 38657867
2023 SASH1 promotes stem-like characteristics in human melanocytes, and interacts with tankyrase 2 (TNKS2). Multiple assays confirmed SASH1-TNKS2 binding; the SASH1 S519N variant is located in a bona fide tankyrase-binding motif and alters the binding kinetics and affinity of the interaction, impairing SASH1's role in melanocyte stem cell maintenance. Yeast 2-hybrid screening, biochemical binding assays (binding kinetics/affinity), cell-based stem cell assays, SASH1 S519N variant functional analysis bioRxiv (preprint)preprint Medium 37808724
2024 SASH1 interacts with TNKS2 (tankyrase 2) via a tankyrase-binding motif; the S519N variant alters binding kinetics and affinity. SASH1 regulates melanocyte stem cell (McSC) maintenance, and this function is TNKS2-dependent. SASH1 S519N is defective in promoting stem-like function. Yeast 2-hybrid screening, biochemical binding affinity assays, clinical examination, human cell assays The Journal of investigative dermatology Medium 38848986
2025 SASH1 suppresses TGF-β1 signaling through regulation of THBS1. SASH1 knockdown increases TGF-β1 levels, but THBS1 counteracts this increase. SASH1 inhibits proliferation, migration, invasion, EMT, and promotes melanin synthesis through TGF-β1/THBS1 signaling. In vivo, SASH1 knockdown A375 cells show enhanced tumor growth. SASH1/THBS1 modulation by siRNA/overexpression, Western blot/qPCR (SASH1/THBS1/TGF-β1 pathway), cell phenotype assays, melanin synthesis measurement, in vivo xenograft Pigment cell & melanoma research Medium 41284354
2026 SASH1 interacts with PKM2 in astrocytes; SASH1 depletion causes increased nuclear accumulation of PKM2, shifts metabolism toward aerobic glycolysis (increased glucose uptake, lactate release, Glut1 and LDHA mRNA expression). A peptide blocking the SASH1-PKM2 interaction reduces astrocytic activation and promotes wound healing in a mouse TBI model. Co-immunoprecipitation (SASH1-PKM2), nuclear fractionation, metabolic assays (glucose uptake, lactate release), qPCR, siRNA knockdown, peptide design, mouse TBI model Brain research Medium 41690666
2016 SASH1 inhibits TGF-β1-mediated EMT, cell migration, and invasion in gastric cancer cells, and inhibits phosphorylation of PI3K and Akt in TGF-β1-stimulated cells, placing SASH1 as a negative regulator of the PI3K/Akt pathway downstream of TGF-β1. SASH1 overexpression, Western blot (PI3K/Akt phosphorylation), migration/invasion assays, EMT marker assays Oncology research Low 27178818
2016 SASH1 inhibits cervical cancer cell proliferation and invasion by suppressing FAK expression and signaling, as shown by reduced FAK protein levels upon SASH1 overexpression. SASH1 overexpression, Western blot (FAK, MMP-2, MMP-9), MTT assay, Transwell assay Molecular medicine reports Low 26935246
2022 SASH1 functions as an astrocytic differentiation-maintaining protein. SASH1 knockdown in spinal astrocytes decreases interferon-γ release, increases BDNF release, and reduces GFAP expression. SASH1 expression increases as NSCs differentiate into glial cells; SASH1 depletion maintains higher Nestin levels and increased BDNF in differentiated NSCs. Co-culture of SASH1-knockdown astrocytes with neurons increases axonal growth and TrkB expression in axonal tips. siRNA knockdown in rat astrocytes, ELISA (IFN-γ, BDNF), Western blot (GFAP, Nestin, TrkB), co-culture axonal growth assay, SCI rat model (in vivo siRNA injection, BBB score) CNS neuroscience & therapeutics Medium 36286186
2023 SASH1 is required for glial cell migration during embryonic brain development. sash1a morpholino knockdown in zebrafish reduces microglial number in the developing brain and causes abnormal arrangement and disordered orientation of gfap+ glia without affecting motor neuron axonal growth. These phenotypes were rescued by injection of human SASH1 mRNA, confirming functional conservation. Morpholino oligonucleotide knockdown in zebrafish, CRISPR/Cas9 mutagenesis, transgenic zebrafish lines (Tg(gfap:eGFP), Tg(hb9:eGFP), Tg(coro1a:eGFP)), human SASH1 mRNA rescue, behavioral assays Developmental biology Medium 37741309

Source papers

Stage 0 corpus · 67 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 SASH1: a candidate tumor suppressor gene on chromosome 6q24.3 is downregulated in breast cancer. Oncogene 122 12771949
2004 C-terminal domain of human CAP18 antimicrobial peptide induces apoptosis in oral squamous cell carcinoma SAS-H1 cells. Cancer letters 110 15279899
2011 The candidate tumor suppressor SASH1 interacts with the actin cytoskeleton and stimulates cell-matrix adhesion. The international journal of biochemistry & cell biology 51 21820526
2013 SASH1 is a scaffold molecule in endothelial TLR4 signaling. Journal of immunology (Baltimore, Md. : 1950) 50 23776175
2013 SASH1 regulates melanocyte transepithelial migration through a novel Gαs-SASH1-IQGAP1-E-Cadherin dependent pathway. Cellular signalling 44 23333244
2012 SASH1 regulates proliferation, apoptosis, and invasion of osteosarcoma cell. Molecular and cellular biochemistry 44 23108792
2014 Autosomal-recessive SASH1 variants associated with a new genodermatosis with pigmentation defects, palmoplantar keratoderma and skin carcinoma. European journal of human genetics : EJHG 43 25315659
2018 The Tumor Suppressor SASH1 Interacts With the Signal Adaptor CRKL to Inhibit Epithelial-Mesenchymal Transition and Metastasis in Colorectal Cancer. Cellular and molecular gastroenterology and hepatology 40 30480076
2016 Overexpression of SASH1 Inhibits TGF-β1-Induced EMT in Gastric Cancer Cells. Oncology research 37 27178818
2012 Effects of SASH1 on lung cancer cell proliferation, apoptosis, and invasion in vitro. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 36 22488244
2005 Differential expression and molecular characterisation of Lmo7, Myo1e, Sash1, and Mcoln2 genes in Btk-defective B-cells. Cellular immunology 36 16137664
2012 Overexpression of SASH1 related to the decreased invasion ability of human glioma U251 cells. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 31 22915266
2017 Involvement of PI3K/Akt pathway in the inhibition of hepatocarcinoma cell invasion and metastasis induced by SASH1 through downregulating Shh-Gli1 signaling. The international journal of biochemistry & cell biology 30 28600143
2012 Effects of SASH1 on melanoma cell proliferation and apoptosis in vitro. Molecular medicine reports 28 23023727
2016 Overexpression of SASH1 Inhibits the Proliferation, Invasion, and EMT in Hepatocarcinoma Cells. Oncology research 27 27178819
2015 SASH1, a new potential link between smoking and atherosclerosis. Atherosclerosis 27 26318107
2020 SASH1 suppresses triple-negative breast cancer cell invasion through YAP-ARHGAP42-actin axis. Oncogene 25 32523092
2016 Activation and cleavage of SASH1 by caspase-3 mediates an apoptotic response. Cell death & disease 25 27831555
2016 A novel P53/POMC/Gαs/SASH1 autoregulatory feedback loop activates mutated SASH1 to cause pathologic hyperpigmentation. Journal of cellular and molecular medicine 24 27885802
2021 CircRNA Circ-ITCH Inhibits the Proliferation and Invasion of Glioma Cells Through Targeting the miR-106a-5p/SASH1 Axis. Cell transplantation 22 33571015
2015 SASH1 inhibits proliferation and invasion of thyroid cancer cells through PI3K/Akt signaling pathway. International journal of clinical and experimental pathology 22 26722413
2021 The emerging and diverse roles of the SLy/SASH1-protein family in health and disease-Overview of three multifunctional proteins. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 21 33710696
2016 Lentiginous phenotypes caused by diverse pathogenic genes (SASH1 and PTPN11): clinical and molecular discrimination. Clinical genetics 21 27659786
2020 SASH1 promotes melanin synthesis and migration via suppression of TGF-β1 secretion in melanocytes resulting in pathologic hyperpigmentation. International journal of biological sciences 20 32174800
2019 Endothelial Sash1 Is Required for Lung Maturation through Nitric Oxide Signaling. Cell reports 20 31067462
2019 HMGB1 contributes to SASH1 methylation to attenuate astrocyte adhesion. Cell death & disease 19 31138780
2016 SASH1 inhibits cervical cancer cell proliferation and invasion by suppressing the FAK pathway. Molecular medicine reports 19 26935246
2019 Exosomal and extracellular HMGB1 have opposite effects on SASH1 expression in rat astrocytes and glioma C6 cells. Biochemical and biophysical research communications 18 31421824
2018 MicroRNA-17 promotes osteosarcoma cells proliferation and migration and inhibits apoptosis by regulating SASH1 expression. Pathology, research and practice 18 30396754
2015 Clinical Significance of SASH1 Expression in Glioma. Disease markers 17 26424902
2018 MiR-130b promotes the progression of oesophageal squamous cell carcinoma by targeting SASH1. Journal of cellular and molecular medicine 16 30443973
2021 Novel missense mutation of SASH1 in a Chinese family with dyschromatosis universalis hereditaria. BMC medical genomics 15 34174894
2020 Identification of a Novel Mutation in SASH1 Gene in a Chinese Family With Dyschromatosis Universalis Hereditaria and Genotype-Phenotype Correlation Analysis. Frontiers in genetics 14 32849825
2020 Five novel mutations in SASH1 contribute to lentiginous phenotypes in Japanese families. Pigment cell & melanoma research 14 32981204
2022 Depletion of SASH1, an astrocyte differentiation-related gene, contributes to functional recovery in spinal cord injury. CNS neuroscience & therapeutics 12 36286186
2021 Two novel SASH1 mutations in Chinese families with dyschromatosis universalis hereditaria. Journal of clinical laboratory analysis 12 34028087
2014 Promoter methylation assay of SASH1 gene in hepatocellular carcinoma. Journal of B.U.ON. : official journal of the Balkan Union of Oncology 12 25536614
2020 SASH1 Suppresses the Proliferation and Invasion of Human Skin Squamous Cell Carcinoma Cells via Inhibiting Akt Cascade. OncoTargets and therapy 11 32547092
2020 Expression of SASH1 in Preeclampsia and Its Effects on Human Trophoblast. BioMed research international 11 33134379
2013 Promoter methylation assay of SASH1 gene in breast cancer. Journal of B.U.ON. : official journal of the Balkan Union of Oncology 11 24344014
2023 HMGB1/SET/HAT1 complex-mediated SASH1 repression drives glycolysis and metastasis in lung adenocarcinoma. Oncogene 10 37794134
2020 Involvement of SASH1 in the Maintenance of Stable Cell-Cell Adhesion. Biochemistry. Biokhimiia 10 32586229
2018 Regulatory mechanism of microRNA-128 in osteosarcoma tumorigenesis and evolution through targeting SASH1. Oncology letters 10 29805606
2023 Human Endogenous Retrovirus-H-Derived miR-4454 Inhibits the Expression of DNAJB4 and SASH1 in Non-Muscle-Invasive Bladder Cancer. Genes 8 37510314
2020 Mutated SASH1 promotes Mitf expression in a heterozygous mutated SASH1 knock‑in mouse model. International journal of molecular medicine 8 32582980
2017 Correlation of SASH1 expression and ultrasonographic features in breast cancer. OncoTargets and therapy 8 28138250
2022 SAM1 domain of SASH1 harbors distinctive structural heterogeneity. Journal of structural biology 7 36341956
2017 The adaptor SASH1 acts through NOTCH1 and its inhibitor DLK1 in a 3D model of lumenogenesis involving CEACAM1. Experimental cell research 7 28823832
2023 SASH1: A Novel Eph Receptor Partner and Insights into SAM-SAM Interactions. Journal of molecular biology 6 37619706
2024 Blockade of a novel MAP4K4-LATS2-SASH1-YAP1 cascade inhibits tumorigenesis and metastasis in luminal breast cancer. The Journal of biological chemistry 5 38657867
2023 Uncovering a new SASH1 mutation associated with dyschromatosis universalis hereditaria using whole-exome-sequencing: A case report. Medicine 5 37543808
2023 SASH1 contributes to glial cell migration in the early development of the central nervous system. Developmental biology 5 37741309
2022 SASH1 knockdown suppresses TRAF6 ubiquitination to regulate hemangioma progression by mediating EZH2 degradation. Experimental cell research 5 35772492
2024 The downregulation of SASH1 expression promotes breast cancer occurrence and invasion accompanied by the activation of PI3K-Akt-mTOR signaling pathway. Scientific reports 4 39300116
2025 SASH1 Mutations and Hereditary Disorders of Pigmentation: Review of Literature. Pigment cell & melanoma research 3 40511878
2024 SASH1 S519N Variant Links Skin Hyperpigmentation and Premature Hair Graying to Dysfunction of Melanocyte Lineage. The Journal of investigative dermatology 3 38848986
2023 Solution NMR backbone assignment of the SASH1 SLy proteins associated disordered region (SPIDER). Biomolecular NMR assignments 3 37155029
2021 AAV1-Mediated shRNA Knockdown of SASH1 in Rat Bronchus Attenuates Hypoxia-Induced Pulmonary Artery Remodeling. Human gene therapy 3 33297837
2023 SASH1 interacts with TNKS2 and promotes human melanocyte stem cell maintenance. bioRxiv : the preprint server for biology 2 37808724
2024 Gastric cancer cell-derived exosomal miRNA-128-3p promotes angiogenesis by targeting SASH1. Frontiers in oncology 1 39664191
2024 SASH1 is a novel binding partner to disassemble Caskin1 tandem SAM homopolymer through heterogeneous SAM-SAM interaction. The FEBS journal 1 39688081
2026 A peptide drug targeting SASH1-PKM2 interaction promotes recovery of traumatic brain injury in mice. Brain research 0 41690666
2026 Therapeutic Targeting of miR-21 Restores SASH1 and Sensitizes HBV-HCC to Sorafenib. Cancers 0 41899638
2025 Sam-Sam Association Between EphA2 and SASH1: In Silico Studies of Cancer-Linked Mutations. Molecules (Basel, Switzerland) 0 39942820
2025 Case report: Clinicopathological characteristics of SASH1 mutation-related dyschromatosis: a rethinking of the classification of dyschromatosis. Frontiers in genetics 0 40115815
2025 Dyschromatosis universalis hereditaria with SASH1 mutation improved with picosecond laser treatment. Skin health and disease 0 40584949
2025 SASH1 Modulates Melanin Synthesis and Melanoma Cell Metastasis via Suppression of the TGF-β Signaling Pathway. Pigment cell & melanoma research 0 41284354

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