Affinage

SNAI1

Zinc finger protein SNAI1 · UniProt O95863

Length
264 aa
Mass
29.1 kDa
Annotated
2026-06-10
100 papers in source corpus 41 papers cited in narrative 42 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SNAI1 (Snail1) is a SNAG-domain zinc-finger transcription factor that acts principally as a sequence-specific transcriptional repressor at E-box elements and is the central effector of epithelial-mesenchymal transition (EMT) (PMID:22406531, PMID:11245431). Repression is achieved by recruiting epigenetic co-repressor machinery to target promoters: Snail1 binds G9a and DNA methyltransferases to deposit H3K9me2 and DNA methylation at the E-cadherin promoter (PMID:22406531), and engages HDAC1/2 to deacetylate histones at the SNAI2, FASN, and other loci (PMID:31165775, PMID:30013137). Through these activities Snail1 controls a broad target program — silencing CDH1, tight-junction genes (ZO-1, claudin 5, occludin), VDR, telomerase (TERT/TERRA), and lipid-handling genes (FASN, ATGL) — and can also potentiate transcriptional activation when partnered at co-occupied enhancers (PMID:24402316, PMID:25961453, PMID:29059385, PMID:30013137, PMID:27851965). Snail1 additionally autoregulates and cross-regulates within the Snail family, repressing its own and SNAI2 promoters through E-box binding (PMID:16617148, PMID:23665016, PMID:31165775). Snail1 abundance and nuclear retention are governed by an extensive post-translational network: phosphorylation by ERK2 (downstream of DDR2/Src and ECM stiffness/ROCK), Lats2 and STK39 at T203, and aPKC at S249 dictates nuclear accumulation versus FBXL5/CK2-GSK3β-driven ubiquitination and degradation (PMID:23644467, PMID:21952048, PMID:34335956, PMID:30804505, PMID:24157836, PMID:22562247, PMID:27076520), while a panel of deubiquitinases (USP27X, USP9X, USP18, USP22, USP36) and PARP-1-mediated poly(ADP-ribosyl)ation stabilize the protein (PMID:30341066, PMID:35506169, PMID:32742193, PMID:37001578, PMID:37833415, PMID:21577210). Upstream, Snail1 transcription is induced by TGFβ/Smad cooperating with HMGA2, by HIF-1α/2α under hypoxia, and by lactate/acetate-driven chromatin modification, and its mRNA stability is set by HuR sensing of UDP-glucose (PMID:18832382, PMID:21257819, PMID:36735787, PMID:32458971, PMID:31243371). Beyond EMT and metastasis (PMID:25164016, PMID:19188491), Snail1 is required for intestinal stem cell maintenance and lineage choice, neuroectodermal fate during ESC differentiation, hepatic and adipocyte lipid metabolism, nucleolar ribosome biogenesis under ribotoxic stress, and blood-brain barrier integrity (PMID:25759216, PMID:24401905, PMID:30013137, PMID:27851965, PMID:37833415, PMID:25961453).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2001 High

    Established that Snail functions as a direct, sequence-specific transcriptional repressor whose activity depends on its N-terminal SNAG domain, defining its core molecular mechanism beyond E-cadherin.

    Evidence Yeast one-hybrid, EMSA with mutagenesis, and SNAG-domain mutant reporter assays at the aromatase promoter

    PMID:11245431

    Open questions at the time
    • Did not identify the co-repressors recruited via the SNAG domain
    • Single target gene context
  2. 2006 High

    Showed Snail1 negatively autoregulates its own promoter, revealing a feedback loop that bounds Snail1 levels.

    Evidence ChIP, promoter-reporter assays, and E-box mutagenesis

    PMID:16617148

    Open questions at the time
    • Quantitative impact of the loop on EMT dynamics not defined
    • Co-repressors at the autoregulated promoter not identified
  3. 2012 High

    Identified the epigenetic effectors of Snail1 repression, linking it to histone H3K9 methylation and DNA methylation at the E-cadherin promoter.

    Evidence Reciprocal Co-IP, ChIP, and knockdown across EMT models showing G9a/DNMT recruitment

    PMID:22406531

    Open questions at the time
    • Whether G9a/DNMT recruitment generalizes to all Snail1 targets unknown
    • Order of H3K9me2 versus DNA methylation deposition not resolved
  4. 2011 High

    Defined how kinase signaling controls Snail1 nuclear retention and stability, with Lats2 phosphorylation at T203 promoting nuclear retention and EMT activity.

    Evidence In vitro kinase assay, Co-IP, T203 mutagenesis, and in vivo zebrafish/mouse models

    PMID:21952048

    Open questions at the time
    • How the same T203 site integrates inputs from other kinases not addressed
    • Relationship to nuclear export machinery unresolved at this stage
  5. 2013 High

    Connected extracellular collagen sensing to Snail1 stabilization, showing DDR2-Src-ERK2 directly phosphorylates Snail1 to extend its half-life and drive metastasis.

    Evidence In vitro kinase assay, phosphosite mapping, ubiquitylation assays, and in vivo metastasis models

    PMID:23644467

    Open questions at the time
    • Precise ERK2 phosphosite-to-ubiquitin-machinery link not fully mapped
    • Crosstalk with degradative kinases not integrated
  6. 2013 High

    Identified FBXL5 as the nuclear E3 ligase that ubiquitinates Snail1 and impairs its DNA binding, and clarified that Lats2 phosphorylation blocks export but not ubiquitination.

    Evidence shRNA screen, Co-IP, ubiquitination and DNA-binding assays, subcellular fractionation, epistasis with Lats2

    PMID:24157836

    Open questions at the time
    • Whether cytosolic degradation uses a distinct ligase unresolved
    • Stoichiometry of phosphorylation versus ubiquitination not quantified
  7. 2019 High

    Linked epithelial polarity to Snail1 turnover, showing aPKC phosphorylation at S249 degrades Snail1 when polarity is intact, and loss of polarity stabilizes it to license EMT.

    Evidence 3D organoids, S249 mutagenesis, PAR-complex loss-of-function, xenografts, human tissue correlation

    PMID:30804505

    Open questions at the time
    • Ligase coupled to S249 phosphorylation not identified
    • Interplay between S249 and T203 phosphorylation not dissected
  8. 2018 High

    Established deubiquitination as a major Snail1-stabilizing mechanism, with USP27X required for TGFβ-induced Snail1 expression and metastasis.

    Evidence siRNA screen, Co-IP, deubiquitination assay, and in vitro/in vivo invasion-metastasis assays

    PMID:30341066

    Open questions at the time
    • Specificity among multiple Snail1 DUBs not compared
    • Lysine residues targeted not mapped
  9. 2014 High

    Resolved the temporal requirement for Snail1 in metastasis, showing transient rather than continuous expression is sufficient and required to promote dissemination.

    Evidence Inducible SNAIL1 reporter-transgene and deletion in multiple immunocompetent breast cancer mouse models

    PMID:25164016

    Open questions at the time
    • Molecular memory underlying transient-expression sufficiency not defined
    • Cell-of-origin dependence not resolved
  10. 2015 High

    Expanded Snail1 biology beyond cancer, establishing essential roles in intestinal stem cell maintenance, lineage choice, and damage response.

    Evidence Conditional intestinal Snai1 knockout, organoids, lineage tracing, and in vivo radiation model

    PMID:25759216

    Open questions at the time
    • Direct target genes mediating stem cell survival not identified
    • Relationship to EMT program in this context unclear
  11. 2018 High

    Revealed non-EMT metabolic functions, showing Snail1 represses lipogenic and lipolytic genes (FASN, ATGL) via HDAC recruitment to control tissue lipid balance.

    Evidence ChIP, tissue-specific conditional knockouts, promoter-reporter assays, and metabolic phenotyping

    PMID:27851965 PMID:30013137

    Open questions at the time
    • Signals that direct Snail1 to metabolic versus EMT promoters unknown
    • How insulin/non-canonical input couples to Snail1 not fully mapped
  12. 2023 Medium

    Identified lactylation as a metabolic post-translational mark on Snail1, with CBP/p300-mediated lactylation driving endothelial transition and EMT downstream of glycolysis.

    Evidence Co-IP, lactylation assays, MCT inhibition, and in vivo myocardial infarction and xenograft models

    PMID:36735787 PMID:39462429

    Open questions at the time
    • Lactylated residues not definitively mapped
    • Functional interplay with phosphorylation/ubiquitination not addressed
  13. 2023 Medium

    Uncovered a nucleolar role for Snail1 in ribosome biogenesis under stress, with JNK-USP36 stabilizing nucleolar Snail1 to support tumor cell survival.

    Evidence JNK inhibition, USP36 knockdown, nucleolar fractionation, ribosome biogenesis assays, and in vivo tumor model

    PMID:37833415

    Open questions at the time
    • Direct nucleolar targets/mechanism of ribosome biogenesis support unknown
    • Whether DNA/E-box binding is involved nucleolarly unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the dense network of competing kinases, ligases, deubiquitinases, and metabolic PTMs is integrated to set Snail1 dosage, residence, and target selectivity in a given tissue context remains unresolved.
  • No unified quantitative model of Snail1 PTM hierarchy
  • Determinants of repressor versus activator/enhancer behavior not defined
  • Context-specific target gene selection mechanism unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 7 GO:0003677 DNA binding 4
Localization
GO:0005634 nucleus 5 GO:0005730 nucleolus 1 GO:0005829 cytosol 1
Pathway
R-HSA-74160 Gene expression (Transcription) 6 R-HSA-162582 Signal Transduction 4 R-HSA-392499 Metabolism of proteins 4 R-HSA-1266738 Developmental Biology 3 R-HSA-1643685 Disease 3
Partners
FBXL5G9AHDAC1HMGA2LATS2PARP-1STK39USP27X

Evidence

Reading pass · 42 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2012 Snail1 interacts with G9a (a major euchromatin H3K9 methyltransferase) and recruits G9a and DNA methyltransferases to the E-cadherin promoter, leading to H3K9me2 and subsequent DNA methylation-mediated repression of E-cadherin. Co-immunoprecipitation, ChIP, knockdown assays, in vitro and in vivo EMT models The Journal of Clinical Investigation High 22406531
2013 Activation of the collagen I receptor DDR2 stimulates ERK2 activity in a Src-dependent manner; activated ERK2 directly phosphorylates SNAIL1, leading to SNAIL1 nuclear accumulation, reduced ubiquitylation, and increased protein half-life, thereby stabilizing SNAIL1 and promoting breast cancer metastasis. In vitro kinase assay, phosphorylation site mapping, ubiquitylation assays, Co-IP, in vivo metastasis models Nature Cell Biology High 23644467
2006 Snail1 protein binds to an E-box at −146 bp in its own promoter and represses its transcriptional activity, forming a negative feedback regulatory loop that limits Snail1 expression levels. Chromatin immunoprecipitation (ChIP), promoter-reporter assays, E-box mutagenesis Nucleic Acids Research High 16617148
2011 Lats2 kinase interacts with Snail1 in the nucleus and directly phosphorylates Snail1 at residue T203, retaining Snail1 in the nucleus and thereby enhancing its stability and EMT-inducing activity. In vitro kinase assay, Co-IP, phosphorylation site mutagenesis, live-cell bioluminescence screen, in vivo zebrafish and mouse embryo models The EMBO Journal High 21952048
2011 PARP-1 poly(ADP-ribosyl)ates Snail1 both in vitro and in vivo, interacting with Snail1 and stabilizing its protein levels; PARP inhibition downregulates Snail1 protein stability and suppresses EMT phenotypes. In vitro and in vivo poly(ADP-ribosyl)ation assay, Co-IP, knockdown, EMT phenotypic assays Oncogene Medium 21577210
2013 FBXL5 is a nuclear E3 ubiquitin ligase that interacts with Snail1 in the nucleus, promoting its polyubiquitination and impairing its DNA binding; Snail1 is subsequently degraded in the cytosol. Lats2-mediated phosphorylation of Snail1 prevents its nuclear export but not its polyubiquitination by FBXL5. shRNA screening, Co-IP, ubiquitination assay, subcellular fractionation, mutagenesis Nucleic Acids Research High 24157836
2019 aPKC kinases of the PAR polarity complex phosphorylate SNAI1 at S249 under intact apical-basal polarity conditions, promoting SNAI1 protein degradation; loss of polarity prevents aPKC-mediated phosphorylation, stabilizing SNAI1 and promoting EMT. 3D organoid cultures, phosphorylation site mutagenesis, loss-of-function of PAR complex components, xenograft models, human tissue correlation Nature Cell Biology High 30804505
2018 USP27X is a deubiquitinase that directly increases Snail1 stability by counteracting its ubiquitination; USP27X is upregulated by TGFβ during EMT and is required for TGFβ-induced Snail1 expression, cell migration, invasion, and metastasis. siRNA screen, Co-IP, deubiquitination assay, knockdown/overexpression, in vitro invasion, in vivo metastasis assay Cancer Research High 30341066
2019 UDP-glucose inhibits SNAI1 mRNA stability by directly binding to HuR (Hu antigen R), preventing HuR from associating with SNAI1 mRNA; EGFR activation leads to UGDH phosphorylation at Y473, promoting conversion of UDP-glucose to UDP-glucuronic acid, relieving UDP-glucose inhibition and stabilizing SNAI1 mRNA to promote EMT and metastasis. RNA-protein interaction assay, mRNA stability assay, phosphorylation studies, in vitro and in vivo lung cancer models Nature High 31243371
2008 HMGA2 directly binds to the SNAIL1 promoter and acts as a transcriptional regulator of SNAIL1 expression; HMGA2 physically interacts with Smad proteins and cooperates with TGFβ/Smad signaling to increase Smad binding to the SNAIL1 promoter, inducing SNAIL1 expression and EMT. ChIP, promoter-reporter assays, Co-IP, siRNA knockdown, EMT phenotypic assays The Journal of Biological Chemistry High 18832382
2010 Phosphorylation of p68 RNA helicase at Y593 activates transcription of the Snail1 gene by promoting dissociation of HDAC1 from the Snail1 promoter; p68 interacts with the MBD3:Mi-2/NuRD chromatin remodeling complex. ChIP, Co-IP, promoter-reporter assay, mutagenesis of phosphorylation site Oncogene Medium 20676135
2017 TGFβ induces Smad3 recruitment of SETDB1 (histone H3K9 methyltransferase) to the SNAI1 gene locus, where SETDB1 deposits H3K9 methylation opposing Smad3/4-driven H3K9 acetylation, thereby repressing SNAI1 transcription and inhibiting EMT. ChIP, Co-IP, knockdown/overexpression, histone modification analysis EMBO Reports Medium 29233829
2023 Lactate induces association between CBP/p300 and Snail1, leading to lactylation of Snail1 in a monocarboxylate transporter (MCT)-dependent manner; lactylated Snail1 promotes EndoMT and TGF-β/Smad2 pathway activation following hypoxia/myocardial infarction. Co-IP, lactylation assay, MCT inhibitor, siRNA knockdown, in vivo MI model Science Advances Medium 36735787
2024 RHOF promotes PKM2 transcription via c-Myc, enhancing glycolysis and lactate production, which induces lactylation and nuclear translocation of Snail1, thereby driving EMT in pancreatic cancer cells. Western blotting, Co-IP, overexpression/knockdown, xenograft model, lactylation assay Cancer & Metabolism Medium 39462429
2011 HIF-1α and HIF-2α directly activate Snail transcription through a hypoxia-response element (HRE) in the Snail gene promoter; gel shift and ChIP assays confirmed HIF binding to this HRE in vitro and in vivo. Gel shift (EMSA), ChIP, reporter gene assay, siRNA knockdown, HIF-ΔODD overexpression Molecular Cancer Research High 21257819
2019 SNAIL1 employs β-Catenin-LEF1 complexes as downstream effectors: SNAIL1 upregulates LEF1 expression, and LEF1 together with β-Catenin redirects Wnt/β-Catenin signaling toward pro-invasive gene expression; LEF1 knockout or β-Catenin-binding-deficient LEF1 impairs SNAIL1-driven invasion without affecting full EMT. CRISPR/Cas9 knockout, conditional SNAIL1 expression, transcriptome analysis, xenotransplantation International Journal of Cancer Medium 31463973
2001 Snail (SnaH) directly binds to a regulatory region (5'-CTGATGAAGT-3') near promoter I.3 of the human aromatase gene and represses its activity; the N-terminal SNAG domain of Snail is required for this repressor activity. Yeast one-hybrid screen, DNA mobility shift assay, mutagenesis, mammalian cell transfection/reporter assay, stable cell line with aromatase mRNA measurement Cancer Research High 11245431
2012 CK2 holoenzyme (requiring the CK2β regulatory subunit) negatively regulates Snail1 stability through synergistic hierarchical phosphorylation in concert with GSK3β; loss of CK2β relieves this suppression, inducing Snail1 accumulation and EMT. Overexpression/knockdown, phosphorylation assays, stability assays, EMT phenotypic assays Oncogene Medium 22562247
2019 SNAI1 recruits HDAC1 and HDAC2 to E-box sequences in the SNAI2 promoter to repress SNAI2 transcription through histone deacetylation. ChIP, HDAC inhibitor treatment, Co-IP, luciferase reporter assay, overexpression Scientific Reports Medium 31165775
2018 Snail1 binds to the TERT promoter and TERRA loci and represses telomerase (TERT) and telomeric repeat-containing RNA (TERRA) expression, thereby controlling telomere integrity in mesenchymal stem cells. FISH, ChIP, RNA expression analysis, conditional Snail1 depletion, telomerase activity assay Nucleic Acids Research Medium 29059385
2013 Snail1 directly binds to the promoter of the Cezanne2 gene via ChIP and mediates its transcriptional repression in hepatocellular carcinoma. ChIP, reporter gene assay, Co-immunoprecipitation Oncogene Medium 23792447
2009 Mesenchymal cells (fibroblasts) reactivate Snail1 expression in response to proliferative/invasive agonists; Snail1-deficient fibroblasts show defects in MT1-MMP-dependent 3D invasive activity and fail to invade or induce angiogenesis in the chick CAM assay. Conditional Snai1 knockout, 3D ECM invasion assay, gene expression profiling, chick CAM model The Journal of Cell Biology High 19188491
2016 ECM stiffness induces ROCK activity, which increases intracellular tension and integrin signaling to ERK2, leading to nuclear accumulation and stabilization of SNAIL1 in breast tumor cells and cancer-associated fibroblasts; SNAIL1 is required for the fibrogenic response of CAFs to stiff matrix and also influences YAP1 levels/activity. In vitro stiffness-tunable matrices, ROCK inhibition, ERK2 knockdown, SNAIL1 knockdown, in vivo breast tumor model Journal of Cell Science Medium 27076520
2018 Snail1 binds to the fatty acid synthase (FASN) promoter and recruits HDAC1/2 to induce deacetylation of H3K9 and H3K27, thereby repressing FASN promoter activity and suppressing lipogenesis in hepatocytes; this represents a non-canonical insulin-Snail1 pathway. ChIP, hepatocyte-specific Snail1 knockout, overexpression, promoter-reporter assay, metabolic phenotyping in vivo Nature Communications High 30013137
2016 Adipocyte Snail1 suppresses ATGL expression by binding to the ATGL promoter, repressing lipolysis; adipocyte-specific Snail1 deletion increases ATGL expression and lipolysis, causing decreased fat mass and increased liver fat. ChIP, adipocyte-specific conditional Snail1 knockout, ATGL promoter-reporter assay, metabolic phenotyping Cell Reports High 27851965
2015 Conditional knockout of Snai1 in the intestinal epithelium results in apoptotic loss of crypt base columnar stem cells, bias toward secretory lineage differentiation, and failure to mount a proliferative response to radiation-induced damage, establishing a required role for Snai1 in intestinal stem cell maintenance and lineage choice. Conditional Snai1 knockout, intestinal organoid cultures, in vivo radiation damage model, lineage tracing The EMBO Journal High 25759216
2014 During embryonic stem cell differentiation, an endogenous Wnt-mediated increase in Snail1 expression regulates neuroectodermal fate and is required for epiblast stem cell exit and mesoderm commitment, independently of EMT. Isogenic pairs of conditional knockout mouse ESCs, transcriptome analysis, differentiation assays Nature Communications Medium 24401905
2014 Drosophila Snail can potentiate transcriptional activation (in addition to repression) by collaborating with Twist at co-occupied enhancers in the mesoderm; an enriched cis-regulatory motif distinct from E-boxes was identified as essential for enhancer activation. In vivo occupancy mapping (ChIP), expression profiling of staged snail mutant embryos, in vitro enhancer activation assay, in vivo enhancer reporter assay, machine learning motif analysis, in silico mutagenesis Genes & Development High 24402316
2022 MACC1 directly binds to SNAI1 protein and upregulates SNAI1 transcriptional activity, leading to transactivation of FN1 and trans-repression of CDH1, driving EMT and pancreatic cancer metastasis in a MET-independent manner. Co-IP, reporter gene assay, MACC1 overexpression/knockdown, liver metastasis mouse model Cell Death & Disease Medium 36333284
2021 STK39 (a serine/threonine kinase) interacts with and phosphorylates SNAI1 at T203, promoting SNAI1 nuclear retention and stability; STK39 inhibition destabilizes SNAI1, impairs EMT, and reduces metastasis. Co-IP, in vitro kinase assay, phosphorylation site mutagenesis, knockdown/overexpression, in vitro invasion assay, in vivo metastasis model Theranostics Medium 34335956
2023 Ribotoxic stress activates JNK, which activates USP36, leading to USP36-mediated stabilization of Snail1 in the nucleolus; nucleolar Snail1 facilitates ribosome biogenesis and solid tumor cell survival, conferring resistance to homoharringtonine (HHT). JNK inhibition, USP36 knockdown, nucleolar fractionation, ribosome biogenesis assay, Co-IP, in vivo tumor model Nature Communications Medium 37833415
2022 USP9X deubiquitinates and stabilizes Snail1 protein; depletion or pharmacological inhibition of USP9X downregulates Snail1, inhibits cell migration, invasion, and metastasis, and sensitizes triple-negative breast cancer cells to cisplatin and paclitaxel. Co-IP, deubiquitination assay, knockdown/inhibitor, rescue with Snail1 overexpression, in vitro invasion assay, in vivo metastasis model Journal of Cellular Physiology Medium 35506169
2020 USP18 deubiquitinates and stabilizes Snail1 protein in colorectal cancer; USP18 interacts with Snail1, and its overexpression promotes proliferation, migration, and invasion that is reversed by Snail1 knockdown. Co-immunoprecipitation, ubiquitination assay, overexpression/knockdown, rescue experiment Cancer Cell International Medium 32742193
2020 USP22 deubiquitinates and stabilizes Snail1 protein in renal tubular epithelial cells; USP22 depletion reduces Snail1 levels, inhibits EMT, and improves renal pathology in diabetic mice. Co-IP, deubiquitination assay, USP22 knockdown/overexpression, in vivo db/db diabetic mouse model European Journal of Pharmacology Medium 37001578
2020 TRIM2 deubiquitinates and stabilizes Snail1 protein in lung adenocarcinoma; TRIM2 interacts with Snail1 via Co-IP and regulates Snail1 ubiquitination-dependent degradation to promote proliferation and invasion. Co-immunoprecipitation, ubiquitination assay, overexpression/knockdown Cancer Cell International Low 32536816
2013 During chondrogenesis, endogenous SNAI1 and SNAI2 proteins bind to E2-box sequences in both their own and each other's promoters, providing a molecular mechanism for compensatory transcriptional regulation between Snai1 and Snai2 during long bone development. ChIP in differentiating ATDC5 cells, conditional double knockout mouse model Biochemical and Biophysical Research Communications Medium 23665016
2015 GBS and other meningeal pathogens induce Snail1 expression in human brain microvascular endothelial cells via ERK1/2/MAPK signaling and bacterial cell wall components; Snail1 then represses tight junction genes (ZO-1, claudin 5, occludin) at the transcriptional level, facilitating blood-brain barrier disruption and bacterial penetration. Snail1 knockdown/overexpression, dominant-negative Snail1 in zebrafish, ERK1/2 inhibition, tight junction mRNA/protein measurement The Journal of Clinical Investigation High 25961453
2018 The transcription factor scleraxis directly binds E-box sequences in the Snai1 promoter to transactivate Snai1 gene expression; TGFβ-mediated upregulation of Snai1 is completely dependent on scleraxis. ChIP, promoter-reporter assay, scleraxis knockdown/overexpression, epistasis with TGFβ signaling American Journal of Physiology. Heart and Circulatory Physiology Medium 29906225
2010 Snail1 and Snail2 directly repress vitamin D receptor (VDR) gene promoter activity; this repression is specific to the Snail family, as other EMT-inducing transcription factors do not affect VDR expression in colon cancer cells. Promoter-reporter assay, overexpression in colon cancer cells, specificity comparison across EMT transcription factors The Journal of Steroid Biochemistry and Molecular Biology Low 20138990
2019 SNAI1 represses SNAI2 transcription by binding to E-box sequences in the SNAI2 promoter and recruiting HDAC1 to mediate histone deacetylation. ChIP, HDAC inhibitor assay, overexpression, luciferase reporter Scientific Reports Medium 31165775
2014 Transient (but not continuous) SNAIL1 expression in breast cancer primary tumors is sufficient and required to increase metastasis in immunocompetent mouse models; SNAIL1 gene deletion before or after tumor formation blunts metastasis. Genetic SNAIL1 reporter-transgene model, inducible SNAIL1 expression/deletion, multiple immunocompetent breast cancer mouse models Cancer Research High 25164016
2020 Acetate promotes SNAI1 expression under glucose limitation via ACSS2-mediated histone H3K27 acetylation at the SNAI1 regulatory region; ACSS2 knockdown abolishes acetate-induced SNAI1 upregulation and cell migration. ChIP, siRNA knockdown, overexpression, qRT-PCR, migration assay Bioscience Reports Low 32458971

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 747 24168186
2012 G9a interacts with Snail and is critical for Snail-mediated E-cadherin repression in human breast cancer. The Journal of clinical investigation 396 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 379 25084828
2023 Lactate promotes endothelial-to-mesenchymal transition via Snail1 lactylation after myocardial infarction. Science advances 337 36735787
2013 The collagen receptor discoidin domain receptor 2 stabilizes SNAIL1 to facilitate breast cancer metastasis. Nature cell biology 321 23644467
2008 HMGA2 and Smads co-regulate SNAIL1 expression during induction of epithelial-to-mesenchymal transition. The Journal of biological chemistry 305 18832382
2010 Snail: More than EMT. Cell adhesion & migration 216 20168078
2014 Transient SNAIL1 expression is necessary for metastatic competence in breast cancer. Cancer research 189 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 170 31243371
1992 Cloning and developmental expression of Sna, a murine homologue of the Drosophila snail gene. Development (Cambridge, England) 164 1483390
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
2015 Bacterial induction of Snail1 contributes to blood-brain barrier disruption. The Journal of clinical investigation 121 25961453
2014 Epigenetic regulation of EMT: the Snail story. Current pharmaceutical design 109 23888971
2019 Apical-basal polarity inhibits epithelial-mesenchymal transition and tumour metastasis by PAR-complex-mediated SNAI1 degradation. Nature cell biology 106 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 85 24157836
2019 CLDN6 promotes tumor progression through the YAP1-snail1 axis in gastric cancer. Cell death & disease 75 31827075
2014 A conserved role for Snail as a potentiator of active transcription. Genes & development 71 24402316
2005 Switching on-off Snail: LOXL2 versus GSK3beta. Cell cycle (Georgetown, Tex.) 70 16294032
2017 Smad3-mediated recruitment of the methyltransferase SETDB1/ESET controls Snail1 expression and epithelial-mesenchymal transition. EMBO reports 65 29233829
2016 Mechanical signals regulate and activate SNAIL1 protein to control the fibrogenic response of cancer-associated fibroblasts. Journal of cell science 63 27076520
2011 The role of DDX3 in regulating Snail. Biochimica et biophysica acta 63 21237216
2011 Poly(ADP-ribose)-dependent regulation of Snail1 protein stability. Oncogene 63 21577210
2012 Unbalanced expression of CK2 kinase subunits is sufficient to drive epithelial-to-mesenchymal transition by Snail1 induction. Oncogene 62 22562247
2015 Snail1-driven plasticity of epithelial and mesenchymal cells sustains cancer malignancy. Biochimica et biophysica acta 61 26050961
2014 Snail1-dependent control of embryonic stem cell pluripotency and lineage commitment. Nature communications 60 24401905
2019 Snail1: A Transcriptional Factor Controlled at Multiple Levels. Journal of clinical medicine 59 31141910
2014 Zeb1 and Snail1 engage miR-200f transcriptional and epigenetic regulation during EMT. International journal of cancer 59 25178837
2021 SNAIL1: Linking Tumor Metastasis to Immune Evasion. Frontiers in immunology 56 34917071
2009 SNAI1 expression in colon cancer related with CDH1 and VDR downregulation in normal adjacent tissue. Oncogene 56 19802011
2017 The NOTCH1/SNAIL1/MEF2C Pathway Regulates Growth and Self-Renewal in Embryonal Rhabdomyosarcoma. Cell reports 53 28614716
2017 MicroRNA-153-3p suppress cell proliferation and invasion by targeting SNAI1 in melanoma. Biochemical and biophysical research communications 52 28400282
2012 The relationships between snail1 and estrogen receptor signaling in breast cancer cells. Journal of cellular biochemistry 50 22307688
2012 Expression of snail, twist, and Zeb1 in malignant mesothelioma. APMIS : acta pathologica, microbiologica, et immunologica Scandinavica 50 23030626
2018 Insulin/Snail1 axis ameliorates fatty liver disease by epigenetically suppressing lipogenesis. Nature communications 49 30013137
2017 Snail and kidney fibrosis. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 49 28186539
2015 Snai1 regulates cell lineage allocation and stem cell maintenance in the mouse intestinal epithelium. The EMBO journal 47 25759216
2013 Nrf2 and Snail-1 in the prevention of experimental liver fibrosis by caffeine. World journal of gastroenterology 47 24379627
2017 miR-211-5p Suppresses Metastatic Behavior by Targeting SNAI1 in Renal Cancer. Molecular cancer research : MCR 45 28057716
2020 ΔNp63α-induced DUSP4/GSK3β/SNAI1 pathway in epithelial cells drives endometrial fibrosis. Cell death & disease 44 32528070
2013 Compensatory regulation of the Snai1 and Snai2 genes during chondrogenesis. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 44 23322385
2019 SNAIL1 employs β-Catenin-LEF1 complexes to control colorectal cancer cell invasion and proliferation. International journal of cancer 41 31463973
2019 MiR-30a regulates cancer cell response to chemotherapy through SNAI1/IRS1/AKT pathway. Cell death & disease 40 30770779
2009 Snail1 is over-expressed in prostate cancer. APMIS : acta pathologica, microbiologica, et immunologica Scandinavica 40 19245592
2010 The transcription factors Snail1 and Snail2 repress vitamin D receptor during colon cancer progression. The Journal of steroid biochemistry and molecular biology 39 20138990
2021 Epigenetic Regulation and Post-Translational Modifications of SNAI1 in Cancer Metastasis. International journal of molecular sciences 38 34681726
2016 Adipose Snail1 Regulates Lipolysis and Lipid Partitioning by Suppressing Adipose Triacylglycerol Lipase Expression. Cell reports 38 27851965
2011 Snail1 mediates hypoxia-induced melanoma progression. The American journal of pathology 38 21996677
2024 RHOF promotes Snail1 lactylation by enhancing PKM2-mediated glycolysis to induce pancreatic cancer cell endothelial-mesenchymal transition. Cancer & metabolism 37 39462429
2022 MACC1 promotes pancreatic cancer metastasis by interacting with the EMT regulator SNAI1. Cell death & disease 37 36333284
2019 SNAI1 recruits HDAC1 to suppress SNAI2 transcription during epithelial to mesenchymal transition. Scientific reports 37 31165775
2013 Snail1 expression in colorectal cancer and its correlation with clinical and pathological parameters. BMC cancer 37 23522088
2001 Down-regulation of promoter 1.3 activity of the human aromatase gene in breast tissue by zinc-finger protein, snail (SnaH). Cancer research 37 11245431
2010 Phosphorylated p68 RNA helicase activates Snail1 transcription by promoting HDAC1 dissociation from the Snail1 promoter. Oncogene 36 20676135
2015 The role of Snail1 transcription factor in colorectal cancer progression and metastasis. Contemporary oncology (Poznan, Poland) 35 26557772
2020 USP18 directly regulates Snail1 protein through ubiquitination pathway in colorectal cancer. Cancer cell international 34 32742193
2022 LncRNA MILIP links YBX1 to translational activation of Snai1 and promotes metastasis in clear cell renal cell carcinoma. Journal of experimental & clinical cancer research : CR 33 36028903
2017 Targeting Lyn regulates Snail family shuttling and inhibits metastasis. Oncogene 33 28288135
2017 Snail mediates crosstalk between TGFβ and LXRα in hepatocellular carcinoma. Cell death and differentiation 33 29230000
2013 Snail1-dependent transcriptional repression of Cezanne2 in hepatocellular carcinoma. Oncogene 32 23792447
2022 Deubiquitinating enzyme USP9X regulates metastasis and chemoresistance in triple-negative breast cancer by stabilizing Snail1. Journal of cellular physiology 30 35506169
2018 Scleraxis regulates Twist1 and Snai1 expression in the epithelial-to-mesenchymal transition. American journal of physiology. Heart and circulatory physiology 30 29906225
2011 Nematode and snail metallothioneins. Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry 30 21822727
2018 Snail1 transcription factor controls telomere transcription and integrity. Nucleic acids research 29 29059385
2003 Prospero and Snail expression during spider neurogenesis. Development genes and evolution 29 14593479
2020 TRIM2 directly deubiquitinates and stabilizes Snail1 protein, mediating proliferation and metastasis of lung adenocarcinoma. Cancer cell international 28 32536816
2020 Nodakenin alleviated obstructive nephropathy through blunting Snail1 induced fibrosis. Journal of cellular and molecular medicine 28 32696548
2009 Nuclear expression of Snail1 in borderline and malignant epithelial ovarian tumours is associated with tumour progression. BMC cancer 28 19695091
2023 USP36 stabilizes nucleolar Snail1 to promote ribosome biogenesis and cancer cell survival upon ribotoxic stress. Nature communications 27 37833415
2020 Acetate promotes SNAI1 expression by ACSS2-mediated histone acetylation under glucose limitation in renal cell carcinoma cell. Bioscience reports 26 32458971
2018 The calcium channel proteins ORAI3 and STIM1 mediate TGF-β induced Snai1 expression. Oncotarget 26 30034631
2014 Snail1 expression is required for sarcomagenesis. Neoplasia (New York, N.Y.) 26 24947186
2018 Genomewide binding of transcription factor Snail1 in triple-negative breast cancer cells. Molecular oncology 25 29729076
2020 The pond snail Lymnaea stagnalis. EvoDevo 23 33292457
2015 What can be learnt from a snail? Evolutionary applications 23 27087845
2014 Transcription factor Snai1-1 induces osteosarcoma invasion and metastasis by inhibiting E-cadherin expression. Oncology letters 22 24959244
2012 Expression of transcription factor Snai1 and tubulointerstitial fibrosis in progressive nephropathy. Journal of nephrology 22 21725924
2022 LOXL3-promoted hepatocellular carcinoma progression via promotion of Snail1/USP4-mediated epithelial-mesenchymal transition. Environmental toxicology 21 35841383
2018 Snail promotes metastasis of nasopharyngeal carcinoma partly by down-regulating TEL2. Cancer communications (London, England) 21 30253797
2013 MTA3 regulates CGB5 and Snail genes in trophoblast. Biochemical and biophysical research communications 21 23510993
2006 Snail1 gene function during early embryo patterning in mice. Cell cycle (Georgetown, Tex.) 21 17106264
2023 IL-22-Activated MUC13 Impacts on Colonic Barrier Function through JAK1/STAT3, SNAI1/ZEB1 and ROCK2/MAPK Signaling. Cells 19 37174625
2021 STK39 promotes breast cancer invasion and metastasis by increasing SNAI1 activity upon phosphorylation. Theranostics 19 34335956
2019 PGC-1α/SNAI1 axis regulates tumor growth and metastasis by targeting miR-128b in gastric cancer. Journal of cellular physiology 19 30684287
2013 The SNAI1 and SNAI2 proteins occupy their own and each other's promoter during chondrogenesis. Biochemical and biophysical research communications 19 23665016
2023 Dual role of Snail1 as transcriptional repressor and activator. Biochimica et biophysica acta. Reviews on cancer 18 38043804
2017 The regulation of snail: on the ubiquitin edge. Cancer cell & microenvironment 18 29147673
2023 USP22 aggravated diabetic renal tubulointerstitial fibrosis progression through deubiquitinating and stabilizing Snail1. European journal of pharmacology 17 37001578
2022 Edible Snail Production in Europe. Animals : an open access journal from MDPI 17 36290118
2020 Intrastrand backbone-nucleobase interactions stabilize unwound right-handed helical structures of heteroduplexes of L-aTNA/RNA and SNA/RNA. Communications chemistry 17 36703369

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