Affinage

SOX18

Transcription factor SOX-18 · UniProt P35713

Length
384 aa
Mass
40.9 kDa
Annotated
2026-06-10
100 papers in source corpus 41 papers cited in narrative 41 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SOX18 is an HMG-box transcription factor that orchestrates vascular and lymphatic endothelial development by binding the Sox consensus motif AACAAAG and trans-activating target genes through a mapped central activation domain (residues 160–225) and a C-terminal 9-amino-acid motif that recruits the cofactor TAF9 (PMID:7651823, PMID:17603017). Its central developmental role is to act as a molecular switch for lymphatic endothelial differentiation, directly activating Prox1 transcription from cardinal vein cells and inducing the lymphatic program when overexpressed in blood vascular endothelium (PMID:18931657). SOX18 functions within the SOXF family with extensive redundancy: it shares overlapping roles with Sox7 and Sox17 in arteriovenous identity, neovascularization, and early cardiovascular patterning, such that Sox18-null mice are largely normal while combined loss produces severe vascular defects (PMID:11094083, PMID:16895970, PMID:18094332, PMID:17610846). Beyond Prox1, SOX18 directly activates an endothelial and disease-relevant target repertoire including VCAM-1, MMP7, and the barrier protein Claudin-5 (PMID:14634005, PMID:22292085, PMID:24677020), and it cooperates with the MADS-box factor MEF2C, which potentiates SOX18 activity through its activation domain (PMID:11554755). SOX18 uniquely homodimerizes among SOXF proteins via a C-terminal motif, and this dimerization drives its enrichment at endothelial-specific chromatin loci (PMID:30335167). Its activity is shaped by upstream signaling, being enhanced by VEGFD-MEK-ERK signaling that increases nuclear SOX18 (PMID:24269955) and TGF-β1–Smad2/3 (PMID:38417530), and repressed at the promoter by NF-κB acting through HDAC1/2 (PMID:29115856, PMID:35991176). Dominant-negative "ragged" alleles cause cardiovascular and hair follicle defects not by haploinsufficiency but by poisoning the wild-type SOX18 interactome, including loss of MEF2C and SOX7 contacts and disrupted chromatin binding dynamics (PMID:10742113, PMID:11094083, PMID:34570228). SOX18 is a druggable node: small molecules such as Sm4 and the R(+)-propranolol enantiomer inhibit its protein-protein interactions, explaining propranolol's efficacy in infantile hemangioma and HLTRS syndrome (PMID:28137359, PMID:31358114). In cancer it drives tumor angiogenesis, invasion, and an immunosuppressive microenvironment through targets including gp130, MCAM, CCL7, CXCL12, and PD-L1 (PMID:16882943, PMID:29408481, PMID:32616889, PMID:38417530).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1995 High

    Established SOX18 as a sequence-specific DNA-binding transcriptional activator with a defined activation domain, answering whether it functions directly on gene promoters.

    Evidence In vitro DNA binding with bacterially expressed protein and GAL4-SOX18 fusion trans-activation assays

    PMID:7651823

    Open questions at the time
    • No physiological target genes identified at this stage
    • Cellular and developmental context unknown
  2. 2000 High

    Linked SOX18 to cardiovascular and hair follicle development and revealed that disease-causing ragged alleles act dominant-negatively rather than through simple loss of function.

    Evidence Sequencing of Ra alleles with in vitro transcription assays, plus Sox18-null mouse phenotyping

    PMID:10742113 PMID:11094083

    Open questions at the time
    • Molecular basis of the dominant-negative effect not yet defined
    • Identity of redundant compensating factors only inferred
  3. 2001 High

    Identified MEF2C as a direct SOX18 partner that potentiates its activity and explained the dominant-negative ragged effect as loss of MEF2C interaction.

    Evidence Co-immunoprecipitation, endothelial co-localization, and co-transfection transcription assays with wild-type and mutant SOX18

    PMID:11554755 PMID:12748961

    Open questions at the time
    • Structural basis of the SOX18-MEF2C interface not resolved
    • Whether MEF2C cooperation is needed at all endothelial targets unknown
  4. 2003 High

    Defined the first direct in vivo endothelial target gene, VCAM-1, establishing SOX18 control of vascular adhesion gene expression.

    Evidence EMSA, site-directed promoter mutagenesis, and qRT-PCR in Ra-Op mutant mice

    PMID:14634005

    Open questions at the time
    • Broader genome-wide target set not yet mapped
    • Mechanism of target selectivity unknown
  5. 2007 High

    Resolved redundancy within the SOXF family, showing Sox7/Sox17/Sox18 collectively govern arteriovenous identity and neovascularization across mouse and zebrafish.

    Evidence Double-mutant mice and double-morphant zebrafish with vascular marker analysis (Gridlock, EphrinB2, Flt4)

    PMID:16895970 PMID:17610846 PMID:18094332 PMID:18377889

    Open questions at the time
    • Division of labor among paralogs at specific loci unresolved
    • Direct downstream effectors of arteriovenous patterning incompletely defined
  6. 2007 Medium

    Defined a second transactivation module — a C-terminal 9-aa motif binding TAF9 — reconciling contradictory data on truncating SOX18 mutations.

    Evidence Deletion mapping, GAL4 reporter assays, and TAF9 interaction analysis

    PMID:17603017

    Open questions at the time
    • Single lab
    • Contribution of this domain in vivo not directly tested
  7. 2008 High

    Established SOX18 as the molecular switch initiating lymphatic endothelial differentiation by directly activating Prox1, the field-defining mechanistic insight.

    Evidence Proximal Prox1 promoter binding, gain-of-function in blood endothelium, and Sox18-null embryo analysis on a sensitized background

    PMID:18931657

    Open questions at the time
    • Upstream signals triggering the switch not fully defined at this stage
    • Cofactor requirements for Prox1 activation unspecified
  8. 2009 High

    Explained strain-dependent severity of Sox18 loss through compensatory upregulation of normally silent Sox7/Sox17, and detailed microvascular maturation defects in ragged mutants.

    Evidence Genetic modifier analysis, functional substitution assays, and ultrastructural/expression analysis of Ra-Op embryos (MMP7, IL7R, N-cadherin)

    PMID:19429912 PMID:19515696

    Open questions at the time
    • Mechanism that activates compensatory paralog expression unknown
    • Pericyte recruitment defect not mechanistically linked to specific targets
  9. 2010 Medium

    Began mapping upstream transcriptional control of the SOX18 promoter, identifying activators and repressors.

    Evidence Promoter reporter assays, in vitro binding, and mutagenesis for EGR1, Sp3, ZBP-89, and NF-Y

    PMID:18496767 PMID:20054233

    Open questions at the time
    • In vivo relevance of these regulators not tested
    • Integration of multiple inputs on the promoter unresolved
  10. 2013 High

    Connected vascular growth-factor signaling to SOX18, showing VEGFD-MEK-ERK enhances nuclear SOX18 activity and VegfC genetically interacts with sox18 in lymphangiogenesis.

    Evidence Zebrafish and mouse genetic interaction studies with cell-based SOX18 transcription assays; inducible dominant-negative zebrafish

    PMID:23520166 PMID:24269955

    Open questions at the time
    • Direct ERK phosphorylation sites on SOX18 not mapped
    • Quantitative contribution of each signal in vivo unclear
  11. 2014 High

    Defined a SOX18-Claudin-5 axis maintaining endothelial barrier integrity under shear stress, linking SOX18 to vascular homeostasis beyond development.

    Evidence Trans-endothelial resistance with SOX18 gain/loss-of-function and Claudin-5 siRNA rescue, ovine shunt model

    PMID:24677020

    Open questions at the time
    • Mechanosensing pathway upstream of SOX18 not defined
    • Other barrier targets not assessed
  12. 2016 High

    Provided a high-resolution structural basis for SOX18-DNA recognition and demonstrated druggability via DNA decoys, alongside NF-κB-mediated promoter repression in lung injury.

    Evidence 1.75Å crystal structure of the HMG box on a Prox1 element with decoy inhibition; ChIP and promoter mapping of NF-κB repression

    PMID:26939885 PMID:29115856

    Open questions at the time
    • Full-length protein and dimer structure not solved
    • Structural basis of cofactor contacts unknown
  13. 2017 High

    Validated SOX18 protein-protein interactions as a therapeutic vulnerability and identified small molecules (Sm4, marine extracts) and R(+)-propranolol that disrupt them, mechanistically explaining propranolol efficacy in hemangioma and HLTRS.

    Evidence Interactome proteomics, biophysical binding, cell reporters, zebrafish and mouse tumor/HLTRS models; enantiomer-specific dissection

    PMID:28137359 PMID:28163017 PMID:31358114

    Open questions at the time
    • Precise binding sites of inhibitors on SOX18 not all resolved
    • Selectivity against other SOXF proteins incompletely characterized
  14. 2018 High

    Discovered that SOX18 uniquely homodimerizes among SOXF proteins via a C-terminal motif, and that dimerization drives enrichment at endothelial-specific chromatin loci.

    Evidence In vitro binding, split-GFP dimerization in zebrafish, genome-wide ChIP-seq, motif transfer to monomeric SOX7, and a dimerization-disrupting inhibitor

    PMID:30335167

    Open questions at the time
    • Whether all endothelial targets require dimerization unknown
    • Structural detail of the dimer interface not solved
  15. 2021 High

    Defined the multilayered mechanism of the dominant-negative ragged allele, showing it rewires target selection, chromatin binding dynamics, and the wild-type interactome including SOX7 and MEF2C.

    Evidence Single-molecule live-cell imaging, genome-wide ChIP/ATAC-seq, and interactome proteomics comparing wild-type and SOX18RaOp

    PMID:34570228

    Open questions at the time
    • Stoichiometry of poisoning in heterozygous tissue not quantified
    • Therapeutic reversibility not tested
  16. 2025 High

    Extended SOX18 mechanism to disease metabolism and post-transcriptional control, linking it to a mevalonate-pathway axis in hemangioma and to m6A-mediated mRNA destabilization in sepsis cardiomyopathy.

    Evidence Transcriptomics with SOX18 gain/loss and IH xenografts; ChIP, m6A-seq, RNA stability, and Co-IP in LPS cardiomyocyte models (SREBP2/HMGCR; RBM15/YTHDF2/PTX3)

    PMID:39998898 PMID:40093897

    Open questions at the time
    • Generalizability of the mevalonate axis beyond hemangioma unknown
    • Whether m6A regulation operates in vascular tissues untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How SOX18's two transactivation domains, homodimerization, and partner contacts (MEF2C, TAF9, RBPJ, SOX7) are integrated structurally and combinatorially to achieve locus-specific endothelial gene selection remains unresolved.
  • No full-length or dimer-DNA-cofactor structure
  • Rules governing target selectivity across cell types undefined
  • Quantitative hierarchy of upstream signaling inputs unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 5 GO:0003677 DNA binding 3
Localization
GO:0005634 nucleus 2
Pathway
R-HSA-1266738 Developmental Biology 3 R-HSA-1643685 Disease 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-162582 Signal Transduction 2
Partners
MEF2CNKX2.5RBPJSLC12A5SOX7TAF9

Evidence

Reading pass · 41 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 SOX18 protein binds sequence-specifically to the Sox DNA-binding motif AACAAAG and contains a distinct 95 amino acid activation domain (amino acids 160-225) that mediates trans-activation of gene expression through this motif, as demonstrated by bacterially expressed protein and GAL4-SOX18 fusion assays. In vitro DNA binding assay with bacterially expressed protein; GAL4 fusion trans-activation assay Nucleic acids research High 7651823
2000 Point mutations in Sox18 (missense and premature truncation) in two different ragged (Ra) mouse alleles abolish transcriptional trans-activation activity relative to wild-type in vitro, establishing Sox18 as the causative gene for cardiovascular and hair follicle defects in ragged mice. In vitro transcription assay; sequencing of Ra alleles; genetic linkage analysis Nature genetics High 10742113
2000 Sox18-null mice have no cardiovascular defects and only a mild coat defect, indicating that the severe ragged phenotype is due to a dominant-negative effect of the mutant SOX18 proteins rather than haploinsufficiency, and suggesting functional redundancy with Sox7 and/or Sox17. Gene targeting (Sox18-null mice); phenotypic analysis Molecular and cellular biology High 11094083
2001 SOX18 directly interacts with the MADS box transcription factor MEF2C in endothelial cell nuclei; MEF2C potentiates SOX18-mediated transcription and regulates the SOX18 activation domain. Ragged mutant SOX18 proteins (Ra, RaJ) fail to interact with MEF2C, explaining the dominant-negative effect. Co-immunoprecipitation; co-localization in endothelial cells; co-transfection transcription assays Biochemical and biophysical research communications High 11554755
2001 Sox18 is transiently expressed in capillary endothelial cells during the proliferative phase of wound healing angiogenesis in granulation tissue, with identical distribution to Flk-1, but is absent from mature unwounded vessels, establishing Sox18 as a marker and potential regulator of inducible angiogenesis. In situ hybridization; immunostaining in mouse skin wounds Laboratory investigation Medium 11454981
2001 SOX18 directly activates the mu-opioid receptor (mor) distal promoter by binding to multiple Sox consensus motifs within the promoter enhancer, as shown by gel supershift and concentration-dependent luciferase reporter assays. Gel supershift assay; luciferase reporter assay with SOX18 overexpression Molecular pharmacology Medium 11353810
2003 Single-base deletion mutations in Sox18 in the opossum (Ra-op) and ragged-like (Ragl) alleles cause C-terminal frameshifts that abolish transcriptional trans-activation and impair interaction with partner protein MEF2C, acting in a dominant-negative fashion. Sequencing; in vitro transcription assay; MEF2C interaction assay Genesis High 12748961
2003 SOX18 directly binds the VCAM-1 promoter and trans-activates VCAM-1 expression; naturally occurring Sox18 mutant (Ra-Op) attenuates VCAM-1 expression in vitro and in vivo in lung, skin, and skeletal muscle, identifying VCAM-1 as a downstream transcriptional target of SOX18. Transfection; site-specific mutagenesis; gel shift assay; quantitative RT-PCR in Ra-Op mice The Journal of biological chemistry High 14634005
2006 Sox17 and Sox18 have redundant functions in postnatal neovascularization: Sox17(+/-)Sox18(-/-) double mutant mice show reduced neovascularization in liver sinusoids and kidney vasa recta, and primary endothelial cells from these mice are defective in endothelial sprouting and vascular remodeling in vitro. Double mutant mouse generation; histology; in vitro angiogenesis assay with primary endothelial cells Journal of cell science High 16895970
2007 Sox18 contains a novel 9-amino acid transactivation motif in its C-terminal charged block that mediates interaction with transcriptional cofactor TAF9 and constitutes a strong additional transactivation domain, explaining previously contradictory data on Sox18 mutations. Deletion mapping; GAL4 fusion reporter assays; TAF9 interaction analysis Biochemical and biophysical research communications Medium 17603017
2007 In zebrafish, sox18 and sox7 play redundant but collectively essential roles in establishing arteriovenous identity; simultaneous morpholino knockdown of both genes causes arteriovenous fusions and loss of venous/arterial identity markers, while single knockdown has minimal effect. Morpholino knockdown in zebrafish; transgenic reporter lines; molecular marker analysis Blood High 18094332
2007 Sox17 and Sox18 have redundant roles in early cardiovascular development in mice: Sox17/Sox18 double-null embryos display more severe defects in anterior dorsal aorta and head/cervical microvasculature than Sox17 single-null, corresponding to sites of weak Sox7 expression. Double knockout mouse generation; whole-mount PECAM staining Biochemical and biophysical research communications High 17610846
2008 Sox18 acts as a molecular switch to induce differentiation of lymphatic endothelial cells: it is expressed in cardinal vein cells that co-express Prox1 and form lymphatic vessels; Sox18 directly activates Prox1 transcription by binding to its proximal promoter; overexpression of Sox18 in blood vascular endothelial cells induces Prox1 and other lymphatic markers; Sox18-null embryos on a sensitized background show complete blockade of lymphatic endothelial differentiation from the cardinal vein. Promoter binding assay; overexpression in endothelial cells; Sox18-null mouse embryo analysis; cellular lineage tracing Nature High 18931657
2008 In zebrafish, simultaneous knockdown of Sox7 and Sox18 causes dysmorphogenesis of the proximal aorta and arteriovenous shunts; morphants display ectopic venous Flt4 marker in the dorsal aorta and reduced artery-specific markers EphrinB2a and Gridlock, suggesting Sox7/Sox18 control arteriovenous identity by regulating Gridlock expression. Morpholino knockdown in zebrafish; gene expression analysis by ISH and RT-PCR Developmental biology High 18377889
2009 Sox7 and Sox17 can functionally substitute for SOX18 in vitro and in vivo as strain-specific modifiers: they are not normally expressed during lymphatic development but are activated specifically in the absence of SOX18 function only in certain mouse strains, revealing a novel compensatory upregulation mechanism. Genetic modifier analysis; in vitro functional substitution assays; expression analysis in Sox18-null mice on different strain backgrounds Development High 19515696
2009 In Ra-Op embryos, SOX18 dysfunction causes enlarged surface capillaries and endothelial barrier breaches by 12.5 dpc with endothelial hyperplasia and impaired pericyte recruitment; downstream targets MMP7, IL7R, and N-cadherin are reduced, implicating SOX18 in transcriptional regulation of genes required for microvascular maturation. Ultrastructural analysis (EM); immunofluorescence; molecular expression analysis in Ra-Op embryos Human molecular genetics Medium 19429912
2008 SOX18 is a potential target for anti-angiogenic cancer therapy: disruption of Sox18 function (Sox18-null or dominant-negative Sox18RaOp mice) reduces allograft tumor growth and microvessel density; dominant-negative SOX18 impairs HUVEC proliferation, migration, and capillary tube formation via disruption of the actin cytoskeleton. Allograft tumor model in Sox18-null and Sox18RaOp mice; BrdU incorporation; MTS assay; Boyden chamber migration; capillary tube formation in vitro Journal of the National Cancer Institute Medium 16882943
2010 EGR1 transcription factor directly activates the SOX18 promoter: three EGR1 binding sites between -89 and +29 bp relative to the transcriptional start site are functionally required for EGR1-induced SOX18 transcription, as shown by in vitro binding assays and mutational analysis. SOX18 promoter reporter assays; in vitro binding assays; site-directed mutagenesis of EGR1 binding sites Experimental & molecular medicine Medium 20054233
2008 Transcription factors Sp3 and ZBP-89 down-regulate, while NF-Y up-regulates, human SOX18 promoter activity by binding the SOX18 promoter region (-200 to -162 bp relative to ATG), as demonstrated by in vitro binding assays and co-transfection experiments. In vitro binding assays; co-transfection reporter assays; mithramycin A treatment Molecular biology reports Medium 18496767
2012 SOX18 directly activates MMP7 transcription in endothelial cells (demonstrated by promoter reporter assay, EMSA, and ChIP), and also regulates guidance molecules ephrin B2 and semaphorin 3G; SOX18 and MMP7 are co-expressed in blood vessels of human skin. Adenoviral overexpression; microarray; ChIP; EMSA; reporter gene assays; RT-PCR; immunohistochemistry PloS one High 22292085
2013 VEGFD modulates SOX18-mediated transcription through MEK-ERK signaling, enhancing nuclear concentration and transcriptional activity of SOX18 in vascular endothelial cells; genetic interaction between Vegfd and Sox18 is required for normal vascular development in both zebrafish and mice. Zebrafish double morphant; Sox18/Vegfd double knockout mice; cell-based SOX18 transcription assay; signaling pathway analysis Blood High 24269955
2013 Sox18 genetically interacts with VegfC to regulate lymphangiogenesis: combined partial knockdown of sox18 and vegfc in zebrafish has synergistic effects on venous and lymphatic sprouting from the cardinal vein, and Sox18 is required specifically for lymphangiogenesis after arteriovenous differentiation. Zebrafish morpholino knockdown; inducible dominant-negative Sox18 transgenic zebrafish; thoracic duct formation analysis Arteriosclerosis, thrombosis, and vascular biology High 23520166
2014 Sox18 maintains pulmonary endothelial barrier integrity in response to laminar shear stress by upregulating Claudin-5 (CLDN5): shear stress increases Sox18 expression; overexpression of Sox18 enhances trans-endothelial resistance; depletion of Claudin-5 abolishes the Sox18-mediated barrier effect. Trans-endothelial resistance measurement; Sox18 overexpression and knockdown; Claudin-5 siRNA; ovine shunt model Journal of cellular physiology High 24677020
2016 Crystal structure of the SOX18 HMG box bound to a Prox1 DNA element determined at 1.75Å resolution reveals water structure, DNA contact interface, and non-canonical DNA backbone conformations; decoy DNAs based on the Prox1 binding site inhibit SOX18 DNA binding in vitro and suppress SOX18-dependent VCAM1 promoter activity in cells. X-ray crystallography; in vitro DNA binding assay; luciferase reporter assay in COS7 cells; serum stability and nuclease resistance assays Nucleic acids research High 26939885
2016 NF-κB (p65) transcriptionally represses SOX18 expression by binding to a SOX18 promoter sequence between -1,082 and -1,073 bp; this NF-κB-mediated SOX18 downregulation leads to reduced CLDN5 and pulmonary endothelial barrier disruption in LPS-induced acute lung injury; peroxynitrite contributes to NF-κB activation in this context. Promoter reporter assays; ChIP for NF-κB; SOX18 overexpression in HLMVECs and mouse lung; CLDN5 siRNA rescue; LPS in vivo models American journal of respiratory cell and molecular biology High 29115856
2017 A small molecule (Sm4) disrupts a discrete subset of SOX18 protein-protein interactions involving the HMG DNA-binding domain, including SOX18-RBPJ interaction, selectively suppresses SOX18 transcriptional outputs in vitro, interferes with vascular development in zebrafish, and reduces tumour vascular density and metastatic spread in a mouse breast cancer model. Proteomic interactome analysis; biophysical binding assays; zebrafish vascular development assay; mouse breast cancer allograft model; reporter gene assay eLife High 28137359
2017 Small-molecule SOX18 inhibitors identified from a marine extract library interfere with the SOX18 HMG DNA-binding domain, disrupt HMG-dependent protein-protein interaction with RBPJ, and perturb SOX18 transcriptional activity in a cell-based reporter system. Marine extract library screen; in vitro binding assay; cell-based SOX18 reporter gene assay Cell chemical biology Medium 28163017
2017 SOX18 regulates the differentiation of dermal papilla in all hair types: dominant-negative Sox18 (opossum) prevents dermal papilla from inducing hair in regeneration assays; downstream effectors WNT5A and TNC are identified by microarray as potential SOX18 targets regulating epidermal WNT signalling. Dominant-negative Sox18 mouse; fate tracing; microarray; hair regeneration assay with dermal papilla spheres Development Medium 28512199
2018 SOX18 uniquely forms homodimers (among SOXF proteins) via a novel motif in the vicinity of the C-terminus of the DNA-binding region; SOX18 dimerization drives enrichment at endothelial-specific chromatin loci containing SOX dimer binding motifs; a small-molecule inhibitor that disrupts dimerization reduces SOX18 transcriptional activity. In vitro binding assays; split-GFP dimerization reporter in zebrafish; genome-wide ChIP-seq; SOX18 dimerization inhibitor; motif insertion into SOX7 monomer Nucleic acids research High 30335167
2018 miR-7-5p targets the SOX18 3'UTR to suppress SOX18 protein expression, and SOX18 transcriptionally activates gp130 (a subunit of the IL-6 receptor), activating gp130/JAK2/STAT3 signaling in pancreatic cancer cells. Luciferase reporter assay (miRNA target); Western blot; ChIP assay for SOX18 on gp130 promoter; gp130/JAK2/STAT3 pathway analysis Biochemical and biophysical research communications Medium 29408481
2019 R(+)-propranolol is a small-molecule inhibitor of the SOX18 transcription factor, acting independently of beta-adrenergic receptor blockade; this mechanism explains propranolol's therapeutic effect in infantile hemangioma and HLTRS syndrome, and is demonstrated in a mouse model of HLTRS (corneal neo-vascularisation rescue) and a patient-derived hemangioma model. Mouse HLTRS model; in vitro infantile hemangioma model; molecular mechanism dissection distinguishing R(+) from S(-) enantiomer eLife High 31358114
2020 SOX18 transcriptionally activates MCAM and CCL7, which are required for SOX18-mediated gastric cancer invasion and metastasis; a CCL7-CCR1-SOX18 positive feedback loop operates via the ERK/ELK1 pathway, where CCL7-CCR1 upregulates SOX18 expression. ChIP; luciferase reporter assay; gain/loss-of-function in GC cells; in vivo mouse models; rescue experiments with MCAM and CCL7 Oncogene Medium 32616889
2020 TGF-β1 upregulates SOX18 expression by activating the Smad2/3 complex; SOX18 then transactivates CXCL12 and PD-L1, promoting immunosuppressive tumor microenvironment in hepatocellular carcinoma. ChIP; dual-luciferase reporter assay; flow cytometry; orthotopic allografts; hepatocyte-specific knockin/knockout mice; AAV8 delivery Gastroenterology High 38417530
2020 SLC12A5 interacts with and stabilizes SOX18 protein, and the SLC12A5-SOX18 complex upregulates MMP7 to enhance bladder urothelial carcinoma progression. Co-immunoprecipitation; in vitro and in vivo functional assays; gene expression analysis Cancer science Medium 32449280
2020 SOX18 enhances KSHV genome copy numbers and binds to viral origins of replication in lymphatic endothelial cells; chemical or genetic inhibition of SOX18 reduces KSHV genome copies, supporting a role for SOX18 in viral genome maintenance. ChIP for SOX18 on viral origins of replication; genetic depletion; chemical inhibition; quantification of viral genome copies Cancer research Medium 32518203
2021 Dominant-negative SOX18 (SOX18RaOp) disrupts multiple functional layers of wild-type SOX18: it alters target gene selection genome-wide, impairs chromatin binding dynamics, and poisons the wild-type SOX18 interactome including regulatory nodes SOX7 and MEF2C; revealed by single-molecule imaging in living cells, genomics, and proteomics. Single-molecule imaging (three assays); genome-wide ChIP/ATAC-seq; proteomics interactome analysis; comparison of wild-type vs. dominant-negative in living cells Nucleic acids research High 34570228
2022 NF-κB-mediated repression of Sox18 in LPS-induced acute lung injury requires HDAC1 and HDAC2: selective siRNA depletion of HDACs 1 and 2 prevents LPS-mediated Sox18 repression; HDAC1 associates with a transcription-repressive complex at the NF-κB-binding site of the Sox18 promoter; HDAC1 inhibitor tacedinaline preserves endothelial barrier in vivo. HDAC siRNA depletion; ChIP for HDAC1 at Sox18 promoter; promoter reporter assays; endothelial permeability assays; mouse LPS model Frontiers in physiology High 35991176
2022 SOX18 loss-of-function mutation (Lys117*) abolishes trans-activation on target genes NR2F2 and GATA4 and terminates synergistic activation between SOX18 and NKX2.5 in a luciferase reporter assay, identifying NR2F2 and GATA4 as direct transcriptional targets of SOX18 relevant to congenital heart disease. Luciferase reporter assay in HeLa cells; Sanger sequencing; co-transfection with SOX18/NKX2.5 Diagnostics Medium 36010266
2025 SOX18 transcriptionally represses PTX3 under physiological conditions; in sepsis-induced cardiomyopathy, RBM15/YTHDF2-mediated m6A modification destabilizes SOX18 mRNA, reducing SOX18 protein, increasing PTX3, and inducing cardiomyocyte pyroptosis. ChIP; dual-luciferase reporter assay for SOX18-PTX3; m6A-seq; RNA stability assay; co-immunoprecipitation; confocal microscopy; mouse LPS cardiomyocyte model Theranostics High 40093897
2025 An endothelial SOX18-mevalonate pathway (MVP) axis regulates infantile hemangioma pathogenesis: R(+)-propranolol suppresses the MVP via SOX18, which is both necessary and sufficient for this suppression; SOX18 regulates SREBP2 and HMG-CoA reductase (HMGCR); nuclear co-localization of SOX18 and SREBP2 is found in IH patient tissue; statins (HMGCR inhibitors) suppress IH vessel formation in a preclinical xenograft model. Transcriptomic profiling; SOX18 loss- and gain-of-function; IH xenograft model; patient tissue co-localization by IHC The Journal of clinical investigation High 39998898
2013 TNF-α (as well as IL-1 and LPS) represses Sox18 expression in HUVECs through the NF-κB pathway (p65/RelA subunit); adenoviral expression of IκBα prevents Sox18 downregulation; the responsible SOX18 promoter region is within -1.0 kb of the transcriptional start site. Adenoviral IκBα overexpression; Sox18 promoter reporter assays; co-transfection with p65 Biochemical and biophysical research communications Medium 24269235

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 Sox18 induces development of the lymphatic vasculature in mice. Nature 449 18931657
2003 Mutations in the transcription factor gene SOX18 underlie recessive and dominant forms of hypotrichosis-lymphedema-telangiectasia. American journal of human genetics 308 12740761
2000 Mutations in Sox18 underlie cardiovascular and hair follicle defects in ragged mice. Nature genetics 190 10742113
2006 Redundant roles of Sox17 and Sox18 in postnatal angiogenesis in mice. Journal of cell science 175 16895970
2007 Sox18 and Sox7 play redundant roles in vascular development. Blood 165 18094332
2007 Redundant roles of Sox17 and Sox18 in early cardiovascular development of mouse embryos. Biochemical and biophysical research communications 154 17610846
2008 Zebrafish Sox7 and Sox18 function together to control arterial-venous identity. Developmental biology 105 18377889
2000 Mice null for sox18 are viable and display a mild coat defect. Molecular and cellular biology 103 11094083
2024 TGF-β1-Induced SOX18 Elevation Promotes Hepatocellular Carcinoma Progression and Metastasis Through Transcriptionally Upregulating PD-L1 and CXCL12. Gastroenterology 98 38417530
2009 Sox7 and Sox17 are strain-specific modifiers of the lymphangiogenic defects caused by Sox18 dysfunction in mice. Development (Cambridge, England) 84 19515696
2015 Sox7, Sox17, and Sox18 Cooperatively Regulate Vascular Development in the Mouse Retina. PloS one 81 26630461
2006 Effect of disrupted SOX18 transcription factor function on tumor growth, vascularization, and endothelial development. Journal of the National Cancer Institute 79 16882943
2001 SOX18 and the transcriptional regulation of blood vessel development. Trends in cardiovascular medicine 78 11728880
1995 Trans-activation and DNA-binding properties of the transcription factor, Sox-18. Nucleic acids research 77 7651823
2005 SOX7 and SOX18 are essential for cardiogenesis in Xenopus. Developmental dynamics : an official publication of the American Association of Anatomists 73 16193513
2018 LPS-induced Acute Lung Injury Involves NF-κB-mediated Downregulation of SOX18. American journal of respiratory cell and molecular biology 65 29115856
2013 VEGFD regulates blood vascular development by modulating SOX18 activity. Blood 64 24269955
1995 Sequence and expression of Sox-18 encoding a new HMG-box transcription factor. Gene 58 7665083
2017 Pharmacological targeting of the transcription factor SOX18 delays breast cancer in mice. eLife 57 28137359
2003 Sox18 mutations in the ragged mouse alleles ragged-like and opossum. Genesis (New York, N.Y. : 2000) 55 12748961
2001 SOX18 directly interacts with MEF2C in endothelial cells. Biochemical and biophysical research communications 53 11554755
2016 Structure and decoy-mediated inhibition of the SOX18/Prox1-DNA interaction. Nucleic acids research 50 26939885
2003 The VCAM-1 gene that encodes the vascular cell adhesion molecule is a target of the Sry-related high mobility group box gene, Sox18. The Journal of biological chemistry 48 14634005
2019 R-propranolol is a small molecule inhibitor of the SOX18 transcription factor in a rare vascular syndrome and hemangioma. eLife 47 31358114
2001 Sox18 is transiently expressed during angiogenesis in granulation tissue of skin wounds with an identical expression pattern to Flk-1 mRNA. Laboratory investigation; a journal of technical methods and pathology 47 11454981
2019 A Study of High-Grade Serous Ovarian Cancer Origins Implicates the SOX18 Transcription Factor in Tumor Development. Cell reports 44 31825847
2017 Small-Molecule Inhibitors of the SOX18 Transcription Factor. Cell chemical biology 44 28163017
2013 Impact of SOX18 expression in cancer cells and vessels on the outcome of invasive ductal breast carcinoma. Cellular oncology (Dordrecht, Netherlands) 41 24065215
2018 MiR-7-5p functions as a tumor suppressor by targeting SOX18 in pancreatic ductal adenocarcinoma. Biochemical and biophysical research communications 40 29408481
2013 Sox18 genetically interacts with VegfC to regulate lymphangiogenesis in zebrafish. Arteriosclerosis, thrombosis, and vascular biology 39 23520166
2002 Expression of human SOX18 in normal tissues and tumors. International journal of molecular medicine 39 12165811
2009 Vascular defects in a mouse model of hypotrichosis-lymphedema-telangiectasia syndrome indicate a role for SOX18 in blood vessel maturation. Human molecular genetics 38 19429912
2005 Transcription factor SOX18 is expressed in human coronary atherosclerotic lesions and regulates DNA synthesis and vascular cell growth. Arteriosclerosis, thrombosis, and vascular biology 38 16179596
2001 Cloning and functional analysis of the Sry-related HMG box gene, Sox18. Gene 38 11179689
2020 SOX18 promotes gastric cancer metastasis through transactivating MCAM and CCL7. Oncogene 37 32616889
2016 Overexpression of SOX18 promotes prostate cancer progression via the regulation of TCF1, c-Myc, cyclin D1 and MMP-7. Oncology reports 32 27922675
2012 The transcription factor SOX18 regulates the expression of matrix metalloproteinase 7 and guidance molecules in human endothelial cells. PloS one 32 22292085
2007 A novel 9-amino-acid transactivation domain in the C-terminal part of Sox18. Biochemical and biophysical research communications 32 17603017
2010 Contrasting effects of Sox17- and Sox18-sustained expression at the onset of blood specification. Blood 31 20228271
2011 Heterogeneity and degree of TIMP4, GATA4, SOX18, and EGFL7 gene promoter methylation in non-small cell lung cancer and surrounding tissues. Cancer genetics 29 22018271
2015 Silencing NKD2 by promoter region hypermethylation promotes gastric cancer invasion and metastasis by up-regulating SOX18 in human gastric cancer. Oncotarget 28 26396173
2015 SOX18 Is a Novel Target Gene of Hedgehog Signaling in Cervical Carcinoma Cell Lines. PloS one 28 26588701
2016 Suppression of SOX18 by siRNA inhibits cell growth and invasion of breast cancer cells. Oncology reports 26 27108946
2015 Knockdown of SOX18 inhibits the proliferation, migration and invasion of hepatocellular carcinoma cells. Oncology reports 26 26151573
2014 Hypotrichosis-lymphedema-telangiectasia-renal defect associated with a truncating mutation in the SOX18 gene. Clinical genetics 26 24697860
2014 SOX18 expression predicts response to platinum-based chemotherapy in ovarian cancer. Anticancer research 25 25075026
2018 Homodimerization regulates an endothelial specific signature of the SOX18 transcription factor. Nucleic acids research 24 30335167
2015 Aortic Dilatation Associated With a De Novo Mutation in the SOX18 Gene: Expanding the Clinical Spectrum of Hypotrichosis-Lymphedema-Telangiectasia Syndrome. The Canadian journal of cardiology 23 26148450
2020 SLC12A5 interacts and enhances SOX18 activity to promote bladder urothelial carcinoma progression via upregulating MMP7. Cancer science 22 32449280
2020 Oncogenic Herpesvirus Engages Endothelial Transcription Factors SOX18 and PROX1 to Increase Viral Genome Copies and Virus Production. Cancer research 22 32518203
2016 MicroRNAs modulate the expression of the SOX18 transcript in lung squamous cell carcinoma. Oncology reports 22 27666488
2014 Sox18 preserves the pulmonary endothelial barrier under conditions of increased shear stress. Journal of cellular physiology 21 24677020
2016 Methylome analysis for spina bifida shows SOX18 hypomethylation as a risk factor with evidence for a complex (epi)genetic interplay to affect neural tube development. Clinical epigenetics 20 27757173
2017 Genome-wide transcriptomics analysis identifies sox7 and sox18 as specifically regulated by gata4 in cardiomyogenesis. Developmental biology 19 29229250
2014 Adipose tissue-derived stromal cells acquire endothelial-like features upon reprogramming with SOX18. Stem cell research 19 25290189
2001 Transcriptional modulation of mouse mu-opioid receptor distal promoter activity by Sox18. Molecular pharmacology 19 11353810
2018 Role of the SOX18 protein in neoplastic processes. Oncology letters 18 30008814
2017 Influence of miR-7a and miR-24-3p on the SOX18 transcript in lung adenocarcinoma. Oncology reports 18 29115529
2021 A dominant-negative SOX18 mutant disrupts multiple regulatory layers essential to transcription factor activity. Nucleic acids research 16 34570228
2018 Upregulation of SOX18 in colorectal cancer cells promotes proliferation and correlates with colorectal cancer risk. OncoTargets and therapy 16 30555240
2019 Transcription Factor SOX18 Promotes Clear Cell Renal Cell Carcinoma Progression and Alleviates Cabozantinib-Mediated Inhibitory Effects. Molecular cancer therapeutics 15 31527225
2018 Heterogeneous expression and biological function of SOX18 in osteosaroma. Journal of cellular biochemistry 15 29266413
2016 SOX18 Expression in Non-melanoma Skin Cancer. Anticancer research 15 27127146
2000 The human SOX18 gene: cDNA cloning and high resolution mapping. Biochimica et biophysica acta 15 10858556
2019 Down-regulation of SOX18 inhibits laryngeal carcinoma cell proliferation, migration, and invasion through JAK2/STAT3 signaling. Bioscience reports 14 31189744
2017 Dominant-negative Sox18 function inhibits dermal papilla maturation and differentiation in all murine hair types. Development (Cambridge, England) 14 28512199
2015 A novel SOX18 mutation uncovered in Jordanian patient with hypotrichosis-lymphedema-telangiectasia syndrome by Whole Exome Sequencing. Molecular and cellular probes 14 26631803
2001 Sox18 expression in blood vessels and feather buds during chicken embryogenesis. Gene 14 11418236
2022 Loss of SOX18/CLAUDIN5 disrupts the pulmonary endothelial barrier in ventilator-induced lung injury. Frontiers in physiology 13 36620216
2020 Hesperetin ameliorates lipopolysaccharide-induced acute lung injury via the miR-410/SOX18 axis. Journal of biochemical and molecular toxicology 13 32762101
2019 SOX18 Affects Cell Viability, Migration, Invasiveness, and Apoptosis in Hepatocellular Carcinoma (HCC) Cells by Participating in Epithelial-to-Mesenchymal Transition (EMT) Progression and Adenosine Monophosphate Activated Protein Kinase (AMPK)/Mammalian Target of Rapamycin (mTOR). Medical science monitor : international medical journal of experimental and clinical research 13 31427562
2018 Further delineation of the SOX18-related Hypotrichosis, Lymphedema, Telangiectasia syndrome (HTLS). European journal of medical genetics 13 29307792
2017 Interleukin-6 upregulates SOX18 expression in osteosarcoma. OncoTargets and therapy 13 29184419
2015 SOX18 knockdown suppresses the proliferation and metastasis, and induces the apoptosis of osteosarcoma cells. Molecular medicine reports 13 26573263
2000 cDNA cloning, tissue expression, and chromosome mapping of human homolog of SOX18. Journal of human genetics 13 10807548
2025 The m6A modification of SOX18 leads to increased PTX3 and cardiomyocyte pyroptosis in sepsis-induced cardiomyopathy. Theranostics 12 40093897
2023 The maturation of iPS cell-derived brain microvascular endothelial cells by inducible-SOX18 expression. Fluids and barriers of the CNS 12 36732767
2020 Long noncoding RNA LINC01194 enhances the malignancy of laryngeal squamous cell carcinoma by sponging miR-655 to increase SOX18 expression. Biochemical and biophysical research communications 12 32703403
2019 The role of SOX18 in bladder cancer and its underlying mechanism in mediating cellular functions. Life sciences 12 31260682
2025 An endothelial SOX18-mevalonate pathway axis enables repurposing of statins for infantile hemangioma. The Journal of clinical investigation 11 39998898
2020 SP1-induced lncRNA LINC00689 overexpression contributes to osteosarcoma progression via the miR-655/SOX18 axis. European review for medical and pharmacological sciences 11 32196572
2020 SOX18 exerts tumor-suppressive functions in papillary thyroid carcinoma through inhibition of Wnt/β-catenin signaling. Experimental cell research 11 32858034
2022 Identification of SOX18 as a New Gene Predisposing to Congenital Heart Disease. Diagnostics (Basel, Switzerland) 10 36010266
2021 SOX18 enhances the proliferation and migration of airway smooth muscle cells induced by tumor necrosis factor-α via the regulation of Notch1 signaling. International immunopharmacology 10 34004439
2018 A novel autosomal dominant mutation in SOX18 resulting in a fatal case of hypotrichosis-lymphedema-telangiectasia syndrome. American journal of medical genetics. Part A 9 30549413
2010 Early growth response protein 1 acts as an activator of SOX18 promoter. Experimental & molecular medicine 9 20054233
2008 ZBP-89 and Sp3 down-regulate while NF-Y up-regulates SOX18 promoter activity in HeLa cells. Molecular biology reports 9 18496767
2022 NF-κB-dependent repression of Sox18 transcription factor requires the epigenetic regulators histone deacetylases 1 and 2 in acute lung injury. Frontiers in physiology 8 35991176
2020 Augmented angiogenic transcription factor, SOX18, is associated with asthma exacerbation. The Journal of asthma : official journal of the Association for the Care of Asthma 8 32419535
2018 Functional domain analysis of SOX18 transcription factor using a single-chain variable fragment-based approach. mAbs 8 29648920
2017 Taking aim at Sox18. eLife 8 28137360
2017 Expression of SOX18 in Mycosis Fungoides. Acta dermato-venereologica 7 27230943
2013 TNFα-induced down-regulation of Sox18 in endothelial cells is dependent on NF-κB. Biochemical and biophysical research communications 7 24269235
2013 Construction and functional analysis of novel dominant-negative mutant of human SOX18 protein. Biochemistry. Biokhimiia 7 24460943
2023 SOX18 meditates the resistance of Bmi1-expressing cells to cetuximab in HNSCC. Oral diseases 6 37184032
2023 Targeting SOX18 Transcription Factor Activity by Small-Molecule Inhibitor Sm4 in Non-Small Lung Cancer Cell Lines. International journal of molecular sciences 6 37511076
2022 SOX18-associated gene signature predicts sepsis outcome. American journal of translational research 6 35422958
2007 Inhibition of tumor angiogenesis by cell-permeable dominant negative SOX18 mutants. Medical hypotheses 6 17768012
2023 SOX18-enforced expression diverts hemogenic endothelium-derived progenitors from T towards NK lymphoid pathways. iScience 5 37250328
2020 Significance of SOX18 expression in nonmelanoma skin cancers for prediction of high-risk patients: a preliminary study. International journal of dermatology 5 32662888

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