Affinage

SNAI1

Zinc finger protein SNAI1 · UniProt O95863

Length
264 aa
Mass
29.1 kDa
Annotated
2026-04-28
100 papers in source corpus 44 papers cited in narrative 45 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SNAI1 encodes a zinc-finger transcriptional repressor that serves as a master regulator of epithelial-mesenchymal transition (EMT) and also controls mesenchymal cell function, adipocyte lipolysis, and early embryonic lineage decisions. SNAI1 binds E2-box sequences through its ZF1 and ZF2 zinc fingers and represses epithelial target genes—most notably CDH1 (E-cadherin)—by recruiting co-repressor complexes including G9a/DNMT (mediating H3K9me2 and DNA methylation) and LSD1-CoREST (via HMG20A), while also controlling ZEB1 and tight-junction gene expression during EMT (PMID:22406531, PMID:25639869, PMID:21317430, PMID:24297167). SNAI1 protein stability, nuclear retention, and transcriptional activity are governed by a phosphorylation code in which stabilizing kinases (Lats2 and STK39 at T203, ERK2, p38 at S107) oppose a degradation cascade (DYRK2-S104/GSK3β/CK2 phosphorylation leading to β-TrCP-, FBXL5-, and FBXO31-mediated ubiquitination), while multiple deubiquitinases (Dub3, USP27X, USP9X, USP18, USP36, USP37) counteract ubiquitin-dependent turnover to stabilize SNAI1 in response to cytokine, mechanical, and stress signals (PMID:21952048, PMID:34335956, PMID:31209060, PMID:28198361, PMID:30341066, PMID:24157836). Beyond canonical EMT, SNAI1 functions as a metabolic regulator by directly repressing ATGL in adipocytes downstream of insulin signaling, represses its own promoter in a negative-feedback loop, and under ribotoxic stress is stabilized in the nucleolus by USP36 to facilitate ribosome biogenesis (PMID:27851965, PMID:16617148, PMID:37833415).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2006 High

    Establishing that SNAI1 auto-represses its own promoter via an E-box revealed a built-in negative feedback loop, raising the question of how SNAI1 expression is dynamically tuned during EMT.

    Evidence ChIP of endogenous SNAI1 at its own promoter E-box, reporter mutagenesis, and ectopic expression in epithelial cells

    PMID:16617148

    Open questions at the time
    • Whether the auto-repressive loop operates in all tissue contexts
    • Quantitative contribution of auto-repression versus upstream signals to SNAI1 dynamics
  2. 2008 High

    Identification of HMGA2 and Smad-dependent transcriptional activation of the SNAI1 promoter connected TGF-β signaling directly to SNAI1 gene induction, establishing the upstream pathway for EMT initiation.

    Evidence ChIP and Co-IP showing HMGA2-Smad binding at the SNAI1 promoter, reporter assays, functional rescue

    PMID:18832382

    Open questions at the time
    • Whether HMGA2-Smad cooperativity is tissue-restricted
    • Relative contribution versus other SNAI1 promoter activators such as HIF
  3. 2009 High

    Conditional Snail1 knockout in fibroblasts demonstrated that SNAI1 is required for normal mesenchymal cell functions—3D invasion and angiogenesis—extending its role beyond epithelial-to-mesenchymal conversion.

    Evidence Conditional knockout mouse fibroblasts, 3D collagen invasion assay, chorioallantoic membrane angiogenesis assay

    PMID:19188491

    Open questions at the time
    • Whether invasion defects are solely via MT1-MMP or involve additional targets
    • Mesenchymal transcriptional program governed by SNAI1 beyond identified targets
  4. 2011 High

    Multiple studies converged to define how SNAI1 protein stability is regulated: Lats2 phosphorylation at T203 retains SNAI1 in the nucleus to enhance EMT, while PARP-1-mediated poly(ADP-ribosyl)ation independently stabilizes SNAI1—establishing that post-translational modifications constitute a critical regulatory layer beyond transcriptional control.

    Evidence In vitro kinase assay (Lats2/T203), in vitro and in vivo PARylation assay (PARP-1), mutagenesis, zebrafish/mouse embryo and EMT cell models

    PMID:21577210 PMID:21952048

    Open questions at the time
    • Whether PARylation and T203 phosphorylation act on the same or distinct SNAI1 pools
    • Structural basis for how T203 phosphorylation blocks nuclear export
  5. 2011 High

    Demonstration that SNAI1 is required upstream of ZEB1 induction during TGF-β-driven EMT, and transiently represses Twist1, established the temporal hierarchy of EMT transcription factors with SNAI1 acting as the initiator.

    Evidence siRNA epistasis, TGF-β time-course, ChIP for Ets1/Twist at ZEB1 promoter, quantitative expression analysis

    PMID:21317430 PMID:22006115

    Open questions at the time
    • Whether the SNAI1→ZEB1 hierarchy is universal across cancer types
    • Direct versus indirect mechanisms for Ets1 nuclear translocation by SNAI1
  6. 2012 High

    The discovery that SNAI1 recruits the G9a H3K9 methyltransferase and DNMTs to the CDH1 promoter revealed a dual epigenetic silencing mechanism (histone methylation followed by DNA methylation) explaining stable E-cadherin repression during EMT.

    Evidence Reciprocal Co-IP, ChIP at CDH1 promoter, G9a knockdown with rescue, breast cancer cell lines and xenografts

    PMID:22406531

    Open questions at the time
    • Whether G9a and DNMT recruitment is simultaneous or sequential
    • Genome-wide extent of SNAI1-G9a co-occupancy beyond CDH1
  7. 2013 High

    Structural dissection showed ZF1 and ZF2 are specifically required for E2-box binding, and identification of FBXL5 as a nuclear E3 ligase that ubiquitinates SNAI1 to impair DNA binding revealed that SNAI1 can be inactivated in the nucleus before export.

    Evidence Zinc-finger mutagenesis with DNA-binding assays, Co-IP and ubiquitination assays for FBXL5, functional EMT readouts

    PMID:24157836 PMID:24297167

    Open questions at the time
    • Whether FBXL5-mediated ubiquitination targets specific SNAI1 lysines
    • Crystal structure of SNAI1 zinc fingers bound to E2-box DNA
  8. 2013 High

    ERK2-mediated phosphorylation downstream of collagen receptor DDR2 was shown to stabilize SNAI1 and promote its nuclear accumulation, connecting extracellular matrix signaling to SNAI1 protein fate.

    Evidence In vitro kinase assay, cycloheximide chase, Src-dependence, xenograft metastasis models

    PMID:23644467 PMID:23665016

    Open questions at the time
    • Exact ERK2 phosphorylation site(s) on SNAI1
    • How ERK2 phosphorylation intersects mechanistically with Lats2/T203 and GSK3β pathways
  9. 2015 High

    HMG20A was identified as a bridging factor connecting SNAI1 to the LSD1-CoREST complex, explaining how SNAI1 recruits histone demethylase activity to maintain H3K4 demethylation at epithelial gene promoters.

    Evidence Co-IP, ChIP showing LSD1 occupancy dependent on HMG20A, H3K4me analysis, TGF-β EMT assays

    PMID:25639869

    Open questions at the time
    • Whether HMG20A is required at all SNAI1 target loci or only a subset
    • Direct versus indirect interaction between SNAI1 and LSD1
  10. 2016 High

    Discovery that SNAI1 directly represses ATGL in adipocytes, regulated by insulin, expanded SNAI1 function beyond EMT into metabolic regulation of lipolysis.

    Evidence Adipocyte-specific conditional knockout, ChIP at ATGL promoter, lipolysis and metabolic phenotyping

    PMID:27851965

    Open questions at the time
    • Full set of metabolic gene targets of SNAI1 in adipocytes
    • Whether the SNAG-domain co-repressor complexes used in EMT are the same ones used at ATGL
  11. 2017 High

    Identification of Dub3 as an IL-6-induced deubiquitinase that stabilizes SNAI1, along with subsequent discovery of USP27X as a TGF-β-induced SNAI1 DUB, established that signal-specific deubiquitinases dynamically oppose the constitutive ubiquitin-dependent degradation of SNAI1.

    Evidence In vitro deubiquitinase assays, Co-IP, shRNA with rescue, in vivo metastasis models for Dub3; siRNA screen, Co-IP, ubiquitination assays for USP27X

    PMID:28198361 PMID:30341066

    Open questions at the time
    • Whether Dub3, USP27X, and other DUBs act on the same ubiquitin chains
    • Structural basis for DUB specificity toward SNAI1
  12. 2019 High

    Two discoveries defined opposing phosphorylation switches: aPKC phosphorylation at S249 under intact polarity promotes degradation, while p38 phosphorylation at S107 blocks the DYRK2/GSK3β/β-TrCP degradation cascade, revealing how polarity loss and stress cooperate to stabilize SNAI1.

    Evidence 3D organoid and kinase assays (aPKC/S249); in vitro kinase assays and epistasis with DYRK2/GSK3β (p38/S107)

    PMID:30804505 PMID:31209060

    Open questions at the time
    • Whether aPKC and p38 pathways converge on the same SNAI1 molecules
    • In vivo validation of S107 phosphorylation in human tumors
  13. 2019 High

    Demonstration that UDP-glucose inhibits HuR binding to SNAI1 mRNA, and EGFR-activated UGDH diverts UDP-glucose to relieve this inhibition, revealed a metabolite-mediated post-transcriptional control mechanism for SNAI1 expression.

    Evidence In vitro RNA-protein binding, UGDH Y473 mutagenesis, RNA stability assays, lung cancer metastasis models

    PMID:31243371

    Open questions at the time
    • Whether other metabolites similarly regulate SNAI1 mRNA stability
    • Structural basis of UDP-glucose–HuR interaction
  14. 2023 High

    Two novel regulatory mechanisms emerged: CBP/p300-mediated lactylation of SNAI1 stabilizes the protein and promotes endothelial-to-mesenchymal transition, while JNK-USP36 signaling redirects SNAI1 to the nucleolus to facilitate ribosome biogenesis under ribotoxic stress—demonstrating that SNAI1 has functions beyond canonical transcriptional repression.

    Evidence Lactylation assay with MCT inhibition and in vivo MI model (lactylation); subcellular fractionation, nucleolar imaging, ribosome biogenesis assays, tumor models (USP36/nucleolus)

    PMID:36735787 PMID:37833415

    Open questions at the time
    • Specific SNAI1 residues modified by lactylation
    • Molecular mechanism by which nucleolar SNAI1 promotes ribosome biogenesis
    • Whether lactylation and ubiquitination compete for the same lysines

Open questions

Synthesis pass · forward-looking unresolved questions
  • Outstanding questions include: the full structural basis of SNAI1 interactions with its E2-box targets and co-repressor complexes; how the many stabilizing and destabilizing modifications are integrated on single SNAI1 molecules in real time; and the extent and mechanism of SNAI1's non-EMT functions (ribosome biogenesis, telomere maintenance, metabolic regulation) across tissues.
  • No high-resolution structure of SNAI1 bound to DNA or co-repressor complex
  • No systems-level quantitative model integrating phosphorylation, ubiquitination, PARylation, and lactylation
  • Nucleolar and metabolic functions not yet validated across independent labs

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 9 GO:0003677 DNA binding 4
Localization
GO:0005634 nucleus 7 GO:0005694 chromosome 2 GO:0005730 nucleolus 1
Pathway
R-HSA-74160 Gene expression (Transcription) 10 R-HSA-392499 Metabolism of proteins 9 R-HSA-162582 Signal Transduction 8 R-HSA-4839726 Chromatin organization 3 R-HSA-1266738 Developmental Biology 2 R-HSA-1430728 Metabolism 2 R-HSA-1500931 Cell-Cell communication 2
Partners
FBXL5G9AHMG20ALATS2LSD1PARP1USP27XUSP3
Complex memberships
G9a-DNMT epigenetic complexLSD1-CoREST-HMG20A complexUHRF1-DNMT1-G9a-SNAIL1 complex

Evidence

Reading pass · 45 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2012 SNAI1 interacts with G9a (a euchromatin H3K9 methyltransferase) and recruits G9a and DNA methyltransferases to the E-cadherin (CDH1) promoter, leading to H3K9me2 and subsequent DNA methylation to repress E-cadherin expression during EMT. Co-immunoprecipitation, ChIP, G9a knockdown with rescue experiments, in vitro and in vivo breast cancer models The Journal of clinical investigation High 22406531
2013 Collagen I receptor DDR2 stabilizes SNAIL1 by activating ERK2 (in a Src-dependent manner), which directly phosphorylates SNAIL1, leading to SNAIL1 nuclear accumulation, reduced ubiquitylation, and increased protein half-life. In vitro kinase assay, cycloheximide chase, co-immunoprecipitation, mutagenesis, xenograft metastasis models Nature cell biology High 23644467
2011 Lats2 kinase interacts with SNAIL1 and directly phosphorylates it at residue T203 in the nucleus, retaining SNAIL1 in the nucleus and enhancing its stability and EMT-inducing activity. Kinome RNAi screen, in vitro kinase assay, bioluminescence-based live-cell screen, mouse and zebrafish embryo models The EMBO journal High 21952048
2006 SNAIL1 protein binds to an E-box in its own promoter (at -146 relative to transcription start) and represses its own transcription, establishing a negative feedback loop controlling SNAIL1 expression. ChIP, promoter-reporter assays, E-box mutagenesis, ectopic expression studies Nucleic acids research High 16617148
2013 SNAIL1 zinc fingers ZF1 and ZF2 are specifically required for efficient binding to E-cadherin promoter E2-boxes and for EMT induction, whereas SNAIL2 requires ZF3 or ZF4 for these functions. Structural modeling, mutational analysis of individual zinc fingers, DNA binding assays, functional EMT assays The Journal of biological chemistry High 24297167
2019 aPKC kinases (PAR complex) phosphorylate SNAIL1 at S249 under conditions of intact apical-basal polarity, promoting SNAIL1 protein degradation; loss of polarity prevents this phosphorylation and stabilizes SNAIL1 to promote EMT. 3D organoid cultures, aPKC kinase assays, site-directed mutagenesis (S249), xenograft tumor models, human breast tissue correlation Nature cell biology High 30804505
2011 SNAIL1 controls the expression of ZEB1 during TGF-β-induced EMT by multiple mechanisms: depletion of SNAIL1 prevents ZEB1 mRNA and protein upregulation, SNAIL1 is required for nuclear translocation of Ets1 (which binds the proximal ZEB1 promoter), and SNAIL1 cooperates with Twist for maximal ZEB1 transcription. siRNA knockdown, co-transfection assays, TGF-β treatment time-course, ChIP for Twist/Ets1 binding to ZEB1 promoter The Journal of biological chemistry High 21317430
2008 HMGA2 directly binds the SNAIL1 promoter and cooperates with TGF-β/Smad signaling to regulate SNAIL1 gene expression; physical interaction between HMGA2 and Smads increases Smad binding to the SNAIL1 promoter. ChIP, co-immunoprecipitation, promoter-reporter assays, SNAIL1 knockdown rescue experiments The Journal of biological chemistry High 18832382
2017 Dub3 is a deubiquitinase that interacts with and stabilizes SNAIL1 by removing ubiquitin modifications; IL-6 induces Dub3 expression, which prevents SNAIL1 degradation, and inhibitor WP1130 binds Dub3 to block this stabilization. Co-immunoprecipitation, ubiquitination assay, in vitro deubiquitinase assay, shRNA knockdown, ectopic rescue, in vivo metastasis models Nature communications High 28198361
2018 USP27X is a deubiquitinase that stabilizes SNAIL1 protein; USP27X is upregulated by TGF-β during EMT and is required for TGF-β-induced SNAIL1 expression and EMT in epithelial cells and cancer-associated fibroblasts. siRNA screen, Co-immunoprecipitation, ubiquitination assays, cell migration/invasion assays, in vivo metastasis models Cancer research High 30341066
2013 FBXL5 is a nuclear ubiquitin ligase that interacts with SNAIL1, promoting its polyubiquitination; this impairs SNAIL1 DNA binding and leads to cytosolic proteasomal degradation. Lats2 phosphorylation of SNAIL1 prevents nuclear export but not polyubiquitination by FBXL5. shRNA screening, Co-immunoprecipitation, ubiquitination assay, DNA binding assay, iron depletion and γ-irradiation stress experiments Nucleic acids research High 24157836
2011 PARP-1 poly(ADP-ribosyl)ates SNAIL1 both in vitro and in vivo, and this modification (along with PARP-1 interaction) controls SNAIL1 protein stability; PARP inhibition reduces SNAIL1 protein levels and impairs EMT. In vitro and in vivo PAR assay, Co-immunoprecipitation, PARP-1 knockdown and inhibitor studies, EMT phenotype assays Oncogene High 21577210
2015 SNAIL1 interacts with the LSD1-CoREST histone demethylase complex (via HMG20A), and HMG20A is required for SNAIL1-dependent repression of epithelial genes; HMG20A-depleted cells show reduced LSD1 binding to epithelial gene promoters and increased H3K4 methylation. Co-immunoprecipitation, ChIP, transcriptomics, knockdown studies, TGF-β-induced EMT assays Oncogene High 25639869
2019 UDP-glucose directly inhibits the association of HuR with SNAI1 mRNA, leading to SNAI1 mRNA degradation; EGFR-activated UGDH phosphorylation at Y473 converts UDP-glucose to UDP-glucuronic acid, attenuating UDP-glucose-mediated inhibition and thereby stabilizing SNAI1 mRNA to promote EMT. In vitro RNA-protein binding assays, UGDH phosphorylation mutagenesis, RNA stability assays, lung cancer cell and in vivo metastasis models Nature High 31243371
2019 p38 MAPK directly phosphorylates SNAIL1 at Ser107, and this suppresses DYRK2-mediated Ser104 phosphorylation that is required for GSK3β-dependent SNAIL1 phosphorylation and βTrCP-mediated ubiquitination and degradation, thereby stabilizing SNAIL1. In vitro kinase assays, site-directed mutagenesis, ubiquitination assays, ovarian cancer functional studies Cancer research High 31209060
2009 SNAIL1 is required for normal mesenchymal cell function: Snail1-deficient fibroblasts show defects in MT1-MMP-dependent 3D invasive activity and fail to induce angiogenesis on chick chorioallantoic membrane. Conditional knockout mouse model (Snai1 flox), 3D extracellular matrix invasion assay, gene expression profiling, chorioallantoic membrane assay The Journal of cell biology High 19188491
2016 ECM stiffness activates ROCK, which indirectly increases ERK2 activity via integrin signaling, leading to SNAIL1 nuclear accumulation (avoidance of cytosolic proteasome degradation); nuclear SNAIL1 then drives a fibrogenic response in cancer-associated fibroblasts and influences YAP1 activity. Stiff matrix culture, ROCK inhibition, ERK2 knockdown, subcellular fractionation, in vivo CAF studies Journal of cell science High 27076520
2011 HIF-1α and HIF-2α directly bind a hypoxia-response element (HRE) in the SNAI1 promoter and activate SNAI1 gene transcription in response to hypoxia, thereby stimulating EMT and cell migration. Gel shift assay (EMSA), ChIP, reporter gene analysis with HRE mutation, HIF siRNA knockdown, HIF-ΔODD overexpression Molecular cancer research : MCR High 21257819
2017 SETDB1/ESET, recruited by Smad3, represses SNAIL1 (SNAI1) gene transcription by imposing H3K9 methylation at the SNAI1 gene locus, counteracting H3K9 acetylation promoted by activated Smad3/4 complexes; TGF-β attenuates SETDB1 expression to relieve this repression during EMT. ChIP, histone modification analysis, siRNA knockdown of SETDB1, TGF-β stimulation, reporter assays EMBO reports High 29233829
2023 Lactate induces CBP/p300-mediated lactylation of SNAIL1, stabilizing it and promoting endothelial-to-mesenchymal transition; this is dependent on MCT (monocarboxylate transporter) signaling. Co-immunoprecipitation, lactylation assay, MCT inhibitor (CHC), MCT1 silencing, in vivo myocardial infarction model Science advances High 36735787
2010 Tyrosine-phosphorylated p68 RNA helicase activates SNAIL1 transcription by promoting dissociation of HDAC1 from the SNAIL1 promoter; p68 interacts with the NuRD/MBD3:Mi-2 chromatin remodeling complex. Chromatin immunoprecipitation, co-immunoprecipitation, p68 phosphorylation mutant (Y593), SNAIL1 promoter-reporter assays Oncogene Medium 20676135
2015 DACH1 specifically interacts with SNAIL1 (not SNAIL2) to form a complex that can bind the E-box on the E-cadherin promoter in a SNAIL1-dependent manner; DACH1 inhibits SNAIL1 transcriptional activity leading to E-cadherin activation. Co-immunoprecipitation, ChIP, luciferase reporter assays, gain/loss of function, mouse xenograft model Oncogenesis Medium 25775416
2012 CK2 holoenzyme (dependent on the CK2β regulatory subunit) synergistically with GSK3β hierarchically phosphorylates SNAIL1 to negatively regulate its stability; loss of CK2β promotes SNAIL1 induction and EMT. CK2β depletion in epithelial cells, protein stability assays, kinase inhibition, in vitro phosphorylation Oncogene Medium 22562247
2011 Notch1 intracellular domain (NICD) binds SNAIL1 and induces its ubiquitination and MDM2-dependent degradation, thereby inhibiting SNAIL1-dependent cancer cell invasion. Tandem affinity purification/mass spectrometry, Co-immunoprecipitation, subcellular colocalization, invasion assays in HCC cells and mouse embryonic fibroblasts BMC biology Medium 22128911
2013 SNAIL1 and SNAIL2 proteins bind to E2-box sequences in both their own and each other's promoters during chondrogenesis, providing a cross-regulatory mechanism explaining the genetic redundancy between these two genes. ChIP on endogenous proteins in differentiating ATDC5 chondrogenic cells, mouse Snai1/Snai2 double conditional knockout genetic analysis Biochemical and biophysical research communications Medium 23665016
2016 Adipocyte SNAIL1 binds the ATGL (adipose triacylglycerol lipase) promoter to repress its expression; adipocyte-specific Snail1 deletion increases ATGL expression and lipolysis, decreasing fat mass and increasing liver fat content. Adipocyte-specific conditional knockout mouse, ChIP for SNAIL1 at ATGL promoter, lipolysis assays, metabolic phenotyping Cell reports High 27851965
2017 FBXO31 (SCF E3 ligase component) interacts with SNAIL1 and mediates its ubiquitin- and proteasome-dependent degradation; SNAIL1 phosphorylation (by GSK-3β) and the FBXO31 F-box domain are necessary for this interaction. Co-immunoprecipitation, ubiquitination/proteasome assay, site-specific phosphorylation mutants, in vivo xenograft models Molecular cancer research : MCR Medium 29117943
2021 PLAGL2 activates transcription of deubiquitinase USP37, which then directly interacts with and deubiquitinates SNAIL1 protein; GSK-3β-dependent phosphorylation of SNAIL1 is essential for USP37-mediated deubiquitination. Co-immunoprecipitation, ubiquitination assay, luciferase reporter for USP37 promoter, in vitro and in vivo gastric cancer models Theranostics Medium 33391500
2022 USP9X deubiquitinates and stabilizes SNAIL1, promoting EMT, metastasis, and chemoresistance in triple-negative breast cancer; pharmacological inhibition of USP9X with WP1130 destabilizes SNAIL1. Co-immunoprecipitation, ubiquitination assay, USP9X knockdown/inhibitor, rescue by ectopic SNAIL1, in vivo metastasis models Journal of cellular physiology Medium 35506169
2020 USP18 deubiquitinates and stabilizes SNAIL1 protein in colorectal cancer cells, promoting their proliferation, migration, invasion, and EMT. Co-immunoprecipitation, ubiquitination assay, USP18 overexpression/knockdown, rescue by SNAIL1, functional assays Cancer cell international Medium 32742193
2023 Ribotoxic stress activates the JNK-USP36 signaling axis, which stabilizes SNAIL1 in the nucleolus; nucleolar SNAIL1 facilitates ribosome biogenesis and promotes solid tumor cell survival during ribotoxic stress. JNK/USP36 signaling inhibition, subcellular fractionation, SNAIL1 nucleolar localization imaging, ribosome biogenesis assays, in vivo tumor models Nature communications Medium 37833415
2021 STK39 kinase interacts with and phosphorylates SNAIL1 at T203, which is critical for SNAIL1 nuclear retention and stability, thereby promoting EMT, invasion, and metastasis in breast cancer. In vitro kinase assay, site-directed mutagenesis (T203), Co-immunoprecipitation, subcellular fractionation, in vivo breast cancer metastasis model Theranostics High 34335956
2015 Bacterial infection induces SNAIL1 expression via the ERK1/2/MAPK signaling cascade and bacterial cell wall components; induced SNAIL1 represses tight junction genes (ZO-1, claudin 5, occludin) at the transcript and protein levels to disrupt the blood-brain barrier. SNAIL1 siRNA/dominant-negative overexpression, ERK1/2 inhibition, zebrafish infection model, permeability assays, qPCR/Western blot of tight junction components The Journal of clinical investigation High 25461453
2015 LASP-1 directly binds SNAIL1 (possibly stabilizing it) and serves as a nuclear hub assembling the UHRF1-DNMT1-G9a-Snail1 epigenetic complex in a CXCL12-dependent manner. Co-immunoprecipitation, mass spectrometry of LASP-1 immunoprecipitates, proximity ligation assays, nuclear fractionation, CXCL12 stimulation Oncogene Medium 25982273
2018 Snail1 represses expression of telomerase gene (TERT) and telomeric repeat-containing RNA (TERRA), and this repression is required for telomere maintenance; Snail1-deficient mouse mesenchymal stem cells show increased TERRA/TERT levels and telomere alterations. FISH (telomere alterations), TERRA/TERT expression analysis, conditional Snail1 knockout in MSCs, TGFβ-induced EMT correlation, transcriptome analysis Nucleic acids research Medium 29059385
2014 In colorectal cancer cells, SNAIL1 upregulates LEF1 and employs β-Catenin-LEF1 complexes to redirect Wnt/β-Catenin target gene activity toward pro-invasive and anti-proliferative gene expression; LEF1 accounts for ~35% of SNAIL1-induced transcriptional changes. Conditional SNAIL1 expression, CRISPR/Cas9 LEF1 knockout and β-Catenin interaction mutant, transcriptome analysis, invasion assays, xenotransplantation International journal of cancer Medium 31463973
2014 In Drosophila, Snail can positively potentiate Twist-mediated enhancer activation; differentially enriched cis-regulatory motifs predict whether Snail represses or activates target genes, with almost 50% of direct targets showing activation. ChIP-seq for in vivo Snail occupancy, expression profiling of staged snail mutant embryos, enhancer reporter assays, machine learning motif analysis Genes & development Medium 24402316
2022 FTO (m6A demethylase) decreases m6A modification and stability of SNAI1 mRNA; IGF2BP2 acts as an m6A reader binding to the 3' UTR of SNAI1 mRNA to promote its stability, and FTO-mediated downregulation of SNAI1 depends on IGF2BP2. m6A RNA immunoprecipitation (MeRIP), RIP assay, actinomycin D mRNA stability assay, FTO overexpression/knockdown, in vivo ovarian cancer models Cancers Medium 36358640
2011 In NMuMG cells, transient SNAIL1 expression is uniquely required for EMT initiation (E-cadherin downregulation), and SNAIL1 transiently represses Twist1 transcription directly; as SNAIL1 levels decrease, Twist1 is upregulated to sustain late EMT. RNAi knockdown, transient TGF-β treatment, quantitative gene expression analysis, epistasis experiments in nontumorigenic and cancer cell lines Molecular cancer research : MCR Medium 22006115
2006 Conditional null Snai1 mouse allele created using Cre-loxP system (flanking promoter and first two exons); deletion recapitulates Snai1-null gastrulation defects, establishing the allele for tissue-specific loss-of-function studies. Conditional knockout generation, Cre-mediated deletion, genetic complementation with null allele Genesis Medium 16397867
2016 Snail1 suppresses adipose ATGL expression by binding the ATGL promoter; insulin increases Snail1 levels in adipocytes, linking nutritional state to Snail1-mediated lipolysis regulation. ChIP for SNAIL1 at ATGL promoter, conditional adipocyte-specific KO, insulin treatment in murine and human adipocytes, lipolysis assays Cell reports High 27851965
2017 Lyn kinase modulates SNAI1 protein localization and stability through the Vav-Rac1-PAK1 pathway; targeting Lyn reduces EMT and metastasis in vitro and in vivo. Lyn knockdown/inhibition, subcellular fractionation, Vav-Rac1-PAK1 pathway inhibitors, in vivo primary tumor metastasis assay Oncogene Medium 28288135
2024 RHOF promotes c-Myc expression, which drives PKM2 transcription, increasing glycolysis and lactate production; lactate causes lactylation of SNAIL1 and its nuclear translocation, promoting EMT in pancreatic cancer cells. Western blotting, co-immunoprecipitation, lactylation assay, SNAIL1 nuclear translocation imaging, Snail1 silencing rescue, xenograft mouse model Cancer & metabolism Medium 39462429
2014 In mouse embryonic stem cells, an endogenous Wnt-mediated burst of SNAIL1 expression during differentiation regulates neuroectodermal fate and is required for epiblast stem cell exit and mesoderm commitment, independent of EMT. Isogenic conditional knockout ESCs, Wnt stimulation, lineage fate analysis, transcriptome profiling Nature communications Medium 24401905
2017 NOTCH1 intracellular domain upregulates SNAIL1 expression to increase tumor-propagating cell number in embryonal rhabdomyosarcoma; SNAIL1 blocks muscle differentiation through suppression of the myogenic transcription factor MEF2C. Zebrafish ERMS transgenic model, SNAIL1 and MEF2C knockdown, tumor transplantation assay, human ERMS cell functional studies Cell reports Medium 28614716

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2013 The Role of Snail in EMT and Tumorigenesis. Current cancer drug targets 739 24168186
2012 G9a interacts with Snail and is critical for Snail-mediated E-cadherin repression in human breast cancer. The Journal of clinical investigation 393 22406531
2014 Central role of Snail1 in the regulation of EMT and resistance in cancer: a target for therapeutic intervention. Journal of experimental & clinical cancer research : CR 373 25084828
2013 The collagen receptor discoidin domain receptor 2 stabilizes SNAIL1 to facilitate breast cancer metastasis. Nature cell biology 321 23644467
2023 Lactate promotes endothelial-to-mesenchymal transition via Snail1 lactylation after myocardial infarction. Science advances 316 36735787
2008 HMGA2 and Smads co-regulate SNAIL1 expression during induction of epithelial-to-mesenchymal transition. The Journal of biological chemistry 304 18832382
2011 Functional cooperation between Snail1 and twist in the regulation of ZEB1 expression during epithelial to mesenchymal transition. The Journal of biological chemistry 247 21317430
2014 Transient SNAIL1 expression is necessary for metastatic competence in breast cancer. Cancer research 188 25164016
2006 Expression of Snail protein in tumor-stroma interface. Oncogene 185 16568079
2019 UDP-glucose accelerates SNAI1 mRNA decay and impairs lung cancer metastasis. Nature 167 31243371
2011 Temporal and spatial cooperation of Snail1 and Twist1 during epithelial-mesenchymal transition predicts for human breast cancer recurrence. Molecular cancer research : MCR 138 22006115
2013 Differential role of Snail1 and Snail2 zinc fingers in E-cadherin repression and epithelial to mesenchymal transition. The Journal of biological chemistry 133 24297167
2006 Snail1 transcriptional repressor binds to its own promoter and controls its expression. Nucleic acids research 133 16617148
2009 Mesenchymal cells reactivate Snail1 expression to drive three-dimensional invasion programs. The Journal of cell biology 127 19188491
2017 Dub3 inhibition suppresses breast cancer invasion and metastasis by promoting Snail1 degradation. Nature communications 122 28198361
2015 Bacterial induction of Snail1 contributes to blood-brain barrier disruption. The Journal of clinical investigation 119 25961453
2014 Epigenetic regulation of EMT: the Snail story. Current pharmaceutical design 108 23888971
2019 Apical-basal polarity inhibits epithelial-mesenchymal transition and tumour metastasis by PAR-complex-mediated SNAI1 degradation. Nature cell biology 105 30804505
2018 miR-145 Antagonizes SNAI1-Mediated Stemness and Radiation Resistance in Colorectal Cancer. Molecular therapy : the journal of the American Society of Gene Therapy 103 29475734
2007 Expression of snail in pancreatic cancer promotes metastasis and chemoresistance. The Journal of surgical research 103 17583745
2011 SNAI1 is involved in the proliferation and migration of glioblastoma cells. Cellular and molecular neurobiology 99 21225336
2012 The role of Snail in prostate cancer. Cell adhesion & migration 96 23076049
2011 Lats2 kinase potentiates Snail1 activity by promoting nuclear retention upon phosphorylation. The EMBO journal 96 21952048
2011 Mouse snail is a target gene for HIF. Molecular cancer research : MCR 94 21257819
2018 TGFβ-Activated USP27X Deubiquitinase Regulates Cell Migration and Chemoresistance via Stabilization of Snail1. Cancer research 93 30341066
2011 Snail1 induces epithelial-to-mesenchymal transition and tumor initiating stem cell characteristics. BMC cancer 93 21929801
2007 Matrix metalloproteinase-induced epithelial-mesenchymal transition: tumor progression at Snail's pace. The international journal of biochemistry & cell biology 91 17416542
2013 Nuclear ubiquitination by FBXL5 modulates Snail1 DNA binding and stability. Nucleic acids research 84 24157836
2015 DACH1 inhibits SNAI1-mediated epithelial-mesenchymal transition and represses breast carcinoma metastasis. Oncogenesis 75 25775416
2019 CLDN6 promotes tumor progression through the YAP1-snail1 axis in gastric cancer. Cell death & disease 73 31827075
2014 A conserved role for Snail as a potentiator of active transcription. Genes & development 70 24402316
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