Affinage

TWIST1

Twist-related protein 1 · UniProt Q15672

Length
202 aa
Mass
21.0 kDa
Annotated
2026-04-28
100 papers in source corpus 46 papers cited in narrative 46 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TWIST1 is a basic helix-loop-helix (bHLH) transcription factor that functions as a master regulator of epithelial-mesenchymal transition (EMT), mesenchymal cell fate, and tissue remodeling by forming context-dependent homo- or heterodimers whose partner choice and transcriptional output are controlled by phosphorylation and acetylation. Non-acetylated TWIST1 recruits the NuRD co-repressor complex to silence epithelial genes such as E-cadherin and FOXA1, whereas diacetylation at K73/K76 switches its interaction to the TIP60-Com co-activator complex via BRD8, enabling activation of mesenchymal and proliferative targets including MYC, Bmi1, FoxM1, and Tie2 (PMID:37680145, PMID:21876555, PMID:27524420, PMID:24204899). Protein stability is tightly regulated by multiple deubiquitinases (USP4, USP13, USP18, USP29) and E3 ligase pathways (FBXL14, Pirh2, G3BP2), with upstream kinases including PKA, Aurora A, and CDK1 controlling dimer composition, ubiquitin susceptibility, and transcriptional potency (PMID:15735646, PMID:28167680, PMID:36782089, PMID:36732432, PMID:30131448). Beyond its canonical role in cancer metastasis and stemness, TWIST1 directs neural crest cell differentiation through a chromatin regulatory module containing CHD7/CHD8/WHSC1, regulates vascular integrity and angiogenesis through the angiopoietin-Tie2 axis, drives tissue fibrosis in lung and skin, and limits Th1 cytokine production to restrain immunopathology (PMID:33554859, PMID:27281171, PMID:37142338, PMID:18663125).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2004 Medium

    Establishing that TWIST1 has oncogenic activity beyond EMT: TWIST1 was shown to cooperate with N-Myc by suppressing the ARF/p53 apoptotic pathway, revealing a pro-survival transcriptional function.

    Evidence cDNA microarray and functional transformation/apoptosis assays in neuroblastoma cells

    PMID:15607966

    Open questions at the time
    • Mechanism of ARF pathway suppression not molecularly defined
    • No direct promoter binding to ARF pathway genes shown
  2. 2005 High

    Resolving how TWIST1 dimer partner choice is determined: PKA-mediated phosphorylation of helix I residues was shown to regulate whether TWIST1 homodimerizes or heterodimerizes with HAND2, and Saethre-Chotzen syndrome mutations disrupt this phosphoregulation.

    Evidence In vivo phosphorylation assays, mouse limb genetics, domain mutagenesis

    PMID:15735646

    Open questions at the time
    • Crystal structure of phosphorylated versus unphosphorylated dimers not resolved
    • Full spectrum of phosphosites controlling partner choice not mapped
  3. 2008 High

    Extending TWIST1 function to immune regulation: TWIST1 was found to be induced in Th1 effector memory cells via NF-κB/NFAT/STAT4 and to limit IFN-γ, IL-2, and TNF-α expression, establishing a negative feedback loop restraining immunopathology.

    Evidence T cell stimulation, transcription factor inhibition, adoptive transfer arthritis models

    PMID:18663125

    Open questions at the time
    • Direct promoter binding to cytokine loci not demonstrated by ChIP
    • Mechanism of transcriptional repression in T cells unclear
  4. 2011 High

    Identifying the NuRD complex as TWIST1's repressive effector: TWIST1 was shown to recruit NuRD to the E-cadherin promoter to repress transcription, and to directly activate Bmi1 via E-box binding, linking EMT to stemness.

    Evidence ChIP, reporter assays, biochemical characterization of bHLH domain

    PMID:21876555 PMID:21919891

    Open questions at the time
    • Which NuRD subunits directly contact TWIST1 not identified
    • Whether NuRD recruitment requires specific post-translational modification state was unknown
  5. 2013 High

    Revealing TWIST1's paracrine and developmental regulatory roles: TWIST1 was shown to induce CCL2 to recruit pro-angiogenic macrophages, to interact with SOX10 via its Twist-box to repress PHOX2B and control neural crest fate, and to recruit p300 to the FoxM1 promoter for proliferative gene activation.

    Evidence In vivo macrophage depletion/rescue, conditional mouse KO with promoter-reporter assays, ChIP

    PMID:23329645 PMID:23555309 PMID:24204899

    Open questions at the time
    • Whether CCL2 induction is direct or indirect not fully resolved
    • Structural basis of SOX10-Twist-box interaction not determined
  6. 2014 High

    Establishing TWIST1 protein stability as a regulatory node: p62/SQSTM1 was shown to stabilize TWIST1 by blocking both proteasomal and autophagosomal degradation, while wild-type p53 recruited Pirh2 to ubiquitinate TWIST1, and E-cadherin was paradoxically shown to be required for TWIST1-induced cell dissemination.

    Evidence Co-IP, autophagy-deficient models, ubiquitination assays, 3D organoid live imaging

    PMID:24590176 PMID:24927592 PMID:30131448

    Open questions at the time
    • Which ubiquitin linkage types are added by Pirh2 not defined
    • How E-cadherin mechanistically promotes dissemination despite being a TWIST1-repressed target remains unresolved
  7. 2015 High

    Demonstrating TWIST1's EMT-independent roles in stem cell maintenance and cell cycle: conditional Twist1 KO in skin depleted keratinocyte stem cells and blocked tumor initiation in a p53-dependent manner, while ChIP confirmed direct binding to Cyclin E1, E2F1, and c-Myc promoters.

    Evidence Conditional KO at multiple carcinogenesis stages, flow cytometry, ChIP, cell cycle analysis

    PMID:25575080 PMID:26013710

    Open questions at the time
    • Whether stem cell depletion is cell-autonomous or requires niche signals not fully resolved
    • Relative contribution of each cell cycle target not dissected
  8. 2016 High

    Defining TWIST1's vascular and fibrotic functions: Ser42 phosphorylation was required for Tie2 regulation and angiogenesis, TGFβ-induced ID proteins shifted TWIST1 toward homodimers to drive fibroblast activation and fibrosis, and EC-specific TWIST1 deletion reduced atherosclerosis.

    Evidence Phospho-mutant constructs, endothelial and fibroblast conditional KOs, bleomycin fibrosis models, ChIP-seq

    PMID:27113414 PMID:27245171 PMID:27281171 PMID:27546376

    Open questions at the time
    • Kinase responsible for Ser42 phosphorylation not identified
    • Whether homodimer-specific target gene sets differ in fibroblasts versus endothelial cells not determined
  9. 2017 High

    Revealing a TWIST1-AURKA mutual stabilization loop: Aurora kinase A phosphorylation of TWIST1 at three sites inhibited ubiquitination and favored homodimerization, while TWIST1 reciprocally prevented AURKA degradation.

    Evidence In vitro kinase assay, ubiquitination assay, phospho-dead/mimic mutants, in vivo tumor formation

    PMID:28167680

    Open questions at the time
    • Whether AURKA phosphorylation sites overlap with PKA sites not clarified
    • Structural mechanism of phosphorylation-dependent ubiquitination resistance unknown
  10. 2018 High

    Expanding the regulatory landscape of TWIST1: upstream enhancers eTw-5/6/7 were shown to physically contact the TWIST1 promoter and be bound by LMX1B/TFAP2, TWIST1 activated CUL2/circ-10720 for EMT, and E2A heterodimer stability was shown to differ from homodimer stability.

    Evidence 4C-seq, CRISPR enhancer deletion causing polydactyly, ChIP, dimer-specific degradation assays

    PMID:28851812 PMID:29844124 PMID:30372441

    Open questions at the time
    • Complete enhancer logic for tissue-specific TWIST1 expression not mapped
    • Functional significance of circular RNA versus mRNA output ratio unknown
  11. 2020 High

    Identifying multiple deubiquitinases and adaptor proteins controlling TWIST1 turnover: USP4, USP18, and the G3BP2/α-parvin axis were each shown to regulate TWIST1 ubiquitination status, and TWIST1 was shown to promote pulmonary hypertension by degrading GATA-6.

    Evidence Co-IP and deubiquitination assays, conditional SMC-specific Twist1 KO, ubiquitination assays with domain mapping

    PMID:30804457 PMID:32368392 PMID:32549341 PMID:32692930

    Open questions at the time
    • Relative contributions of individual DUBs in a single tissue context not compared
    • Whether USP4 and USP18 act on the same or different ubiquitin chain types on TWIST1 not resolved
  12. 2021 High

    Identifying a TWIST1-chromatin regulatory module (CRM) in neural crest: BioID proximity labeling revealed CHD7, CHD8, and WHSC1 as core TWIST1 partners that collectively control NCC differentiation and craniofacial morphogenesis.

    Evidence BioID proximity proteomics, combinatorial knockdown in cells and mouse embryos

    PMID:33554859

    Open questions at the time
    • Whether TWIST1-CRM uses the same acetylation switch as NuRD/TIP60-Com not tested
    • Direct versus indirect interactions within the CRM not fully resolved
  13. 2023 High

    Resolving the acetylation switch governing TWIST1 co-factor choice: K73/K76 diacetylation was shown to switch TWIST1 from NuRD-mediated repression to BRD8/TIP60-Com-mediated activation, and CDK1-phosphorylated USP29 was identified as another stabilizing DUB, while FBXL14 was identified as the E3 ligase counteracted by USP13.

    Evidence Acetylation-mimetic/dead mutants with ChIP-seq and RNA-seq, in vitro kinase and deubiquitination assays, GST-pulldown

    PMID:36732432 PMID:36782089 PMID:37680145

    Open questions at the time
    • Acetyltransferase responsible for K73/K76 acetylation not identified
    • How the acetylation switch integrates with phosphorylation-dependent dimer choice is unknown
    • Whether the NuRD-to-TIP60 switch operates in non-cancer developmental contexts not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • The acetyltransferase writing K73/K76, the structural basis for acetylation-dependent cofactor switching, the integration of phosphorylation and acetylation codes on a single TWIST1 molecule, and the tissue-specific hierarchy among multiple DUBs remain undefined.
  • Identity of K73/K76 acetyltransferase unknown
  • No structural model of TWIST1 bound to NuRD versus TIP60-Com
  • Relative hierarchy of USP4/USP13/USP18/USP29 in physiological tissues not established
  • How enhancer-level and post-translational regulation are coordinated across tissues remains open

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003677 DNA binding 8 GO:0140110 transcription regulator activity 7
Localization
GO:0005634 nucleus 4
Pathway
R-HSA-392499 Metabolism of proteins 7 R-HSA-74160 Gene expression (Transcription) 7 R-HSA-1266738 Developmental Biology 5 R-HSA-162582 Signal Transduction 4 R-HSA-168256 Immune System 2 R-HSA-4839726 Chromatin organization 2
Partners
AURKABRD8E2AHAND2SOX10TRIB3USP29USP4
Complex memberships
NuRD complexTIP60-Com (NuA4)TWIST1-CRM (CHD7/CHD8/WHSC1)

Evidence

Reading pass · 46 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2011 TWIST1 forms homo- or hetero-dimers to bind the Nde1 E-box element and activate or repress target genes; it recruits the nucleosome remodeling and deacetylase (NuRD) complex to directly repress E-cadherin expression during EMT. Biochemical characterization of bHLH domain, chromatin immunoprecipitation, functional reporter assays Cell research High 21876555
2005 Dimerization partner choice by TWIST1 is regulated by protein kinase A- and protein phosphatase 2A-mediated phosphorylation of conserved helix I residues; multiple Saethre-Chotzen syndrome mutations alter PKA-mediated phosphorylation of TWIST1, disrupting normal dimer partner selection between TWIST1 and HAND2. In vivo phosphorylation assays, genetic epistasis in mouse limb, dominant-negative expression, domain mutagenesis Nature genetics High 15735646
2008 Phosphoregulation of specific bHLH domain residues in TWIST1 alters dimerization partner affinities and DNA binding affinity in a cis-element-dependent manner, controlling cell fate decisions. Phosphorylation assays, dimerization partner binding assays, DNA binding (EMSA), mutagenesis Current medicinal chemistry Medium 18855684
2010 TWIST1 binds to the VE-cadherin promoter and enhances its transcriptional activity, while suppressing E-cadherin expression, to promote vasculogenic mimicry in hepatocellular carcinoma. Chromatin immunoprecipitation, transactivation (luciferase) assay, shRNA knockdown, overexpression Hepatology Medium 19957372
2013 TWIST1 expression in mammary epithelial cells induces CCL2 expression (not VEGF or bFGF), which recruits macrophages that are required for the proangiogenic response; attenuation of TWIST1 in vivo blocked macrophage recruitment and angiogenesis. In vitro expression assays, in vivo macrophage depletion, exogenous CCL2 rescue experiments Cancer research High 23329645
2014 p62 (SQSTM1) binds directly to TWIST1 and inhibits its degradation via both autophagosomal and proteasomal pathways, thereby stabilizing TWIST1 protein to promote cell proliferation and migration. Co-immunoprecipitation, autophagy-deficient mouse models, in vivo tumor growth assays Proceedings of the National Academy of Sciences of the USA High 24927592
2013 TGF-β1 upregulates TWIST1 expression through a cascade involving STAT3 phosphorylation and HIF-1α stabilization; both STAT3 and HIF-1α directly bind the TWIST1 promoter, and STAT3 also enhances TWIST1 expression indirectly through HIF-1α stabilization. siRNA silencing, dominant-negative STAT3, chromatin immunoprecipitation, promoter-reporter assays Cancer letters Medium 23623921
2013 TWIST1 interacts with the pro-neural factor SOX10 via its Twist-box domain and binds the PHOX2B promoter to repress its transcriptional activity, thereby controlling neural crest cell fate between ectodermal and mesodermal lineages. Conditional mouse knockout, promoter-reporter (luciferase), protein interaction assays, domain mutagenesis PLoS genetics High 23555309
2014 TWIST1 directly binds the FOXA1 proximal promoter, recruits the NuRD transcriptional repressor complex to de-acetylate H3K9, and inhibits AP-1 recruitment to silence FOXA1 expression, enabling breast cancer invasion and metastasis. ChIP, reporter assays, Co-IP for complex components, reconstitution of FOXA1 rescue in xenograft Oncogene High 27524420
2014 TWIST1 inhibits TRIM29 promoter activity through direct binding to a cluster of E-box elements within the TRIM29 promoter, creating a negative regulatory feedback loop. Promoter-reporter assay, TWIST1 binding to E-box elements Cancer research Medium 24950909
2015 TWIST1 binds directly to the C3 (complement component 3) promoter and enhances its expression; TWIST1 and C3 co-localize at invasive tumor edges and in the neural crest and limb buds of mouse embryos. Promoter-reporter assay, chromatin immunoprecipitation, immunohistochemistry/colocalization Journal of immunology Medium 26718342
2015 TWIST1 conditional knockout in skin reduces keratinocyte stem cell populations (α6-integrin+/CD34+ and label-retaining cells) and blocks tumor initiation and maintenance in a gene-dosage-dependent and partially p53-dependent manner, independent of EMT. Conditional knockout at different carcinogenesis stages, flow cytometry, apoptosis assays, proliferation assays Cell stem cell High 25575080
2016 TWIST1 modulates vascular permeability and angiogenesis by regulating Tie2 expression; knockdown of TWIST1 in endothelial cells decreases Tie2 expression and phosphorylation, increases RhoA activity, disrupts cell-cell junctions, and increases permeability. siRNA knockdown, conditional knockout (Tie2-specific Twist1fl/fl), endothelial permeability assays PloS one High 24023872
2016 TWIST1 phosphorylation at serine 42 (Ser42) is required for its control of angiogenesis through the angiopoietin-Tie2 pathway; a Twist1S42A phosphorylation-dead mutant decreases Tie2 expression and attenuates angiogenesis and collagen deposition in bleomycin-induced pulmonary fibrosis. Phospho-mutant construct, conditional knockout (Twist1fl/fl/Tie2-cre), in vitro sprouting assay, in vivo fibrin gel angiogenesis American journal of respiratory cell and molecular biology High 27281171
2016 TWIST1 homodimers (promoted by TGFβ-induced upregulation of ID proteins that compete for E12/E47) mediate fibroblast activation and tissue fibrosis; TGFβ/SMAD3 pathway induces TWIST1 in fibroblasts, and fibroblast-specific Twist1 deletion protects mice from experimental skin fibrosis. Co-immunoprecipitation (TWIST1, E12, ID proteins), fibroblast-specific conditional KO, bleomycin and TGFβR-constitutive-active models Annals of the rheumatic diseases High 27113414
2016 TWIST1 is induced at low shear stress regions of arteries via a GATA4-dependent transcriptional mechanism, and EC-specific TWIST1 deletion in mice reduces atherosclerosis by inhibiting inflammation and EC proliferation. EC-specific conditional Twist1 KO, carotid artery model, gene silencing, qPCR/en face staining Circulation research High 27245171
2017 Aurora kinase A (AURKA) phosphorylates TWIST1 at three sites, inhibiting its ubiquitination, increasing its transcriptional activity, and favoring its homodimerization; in turn, TWIST1 prevents AURKA degradation, establishing a feedback loop. Phosphorylation-dead TWIST1 acts as a dominant-negative and fully reverses AURKA-induced EMT. In vitro kinase assay, ubiquitination assay, co-immunoprecipitation, phospho-dead/mimic mutants, in vivo tumor formation Journal of cell science High 28167680
2018 TWIST1 binds the CUL2 promoter to activate its transcription and selectively promotes expression of Cul2 circular RNA (circ-10720) over Cul2 mRNA; circ-10720 acts as a miRNA sponge to increase vimentin expression during EMT. ChIP, reporter assays, circ-10720 knockdown, patient-derived xenograft and transgenic mouse models Cancer research High 29844124
2018 Wild-type p53 forms a complex with TWIST1 and the E3 ubiquitin ligase Pirh2 to promote ubiquitination and proteasomal degradation of TWIST1, thereby inhibiting EMT; mutant p53 loses this ability. Co-immunoprecipitation, ubiquitination assays, proteasome inhibition, p53 mutant constructs Molecular cancer research Medium 30131448
2018 TWIST1 and its E2A heterodimeric partners mutually regulate each other's stability post-translationally; the TWIST1-E2A heterodimer is preferentially degraded by harmine compared to TWIST1-TWIST1 homodimer, and E2A proteins are required for TWIST1-mediated functions. Protein stability assays, dimer-specific degradation assays, drug treatment, transgenic and PDX mouse models Molecular cancer research Medium 28851812
2018 MYCN and c-MYC directly bind E-box and INR elements in the TWIST1 promoter and activate its transcription, establishing TWIST1 as a direct MYC transcriptional target in neuroblastoma. Gel shift assay (EMSA), luciferase reporter assay, in silico E-box analysis Cancer letters Medium 25475555
2019 TRIB3 binds the WR domain of TWIST1 and stabilizes it by inhibiting ubiquitination; disruption of the TRIB3-TWIST1 interaction by a peptide analogue promotes TWIST1 degradation and reverses ATRA resistance in APL. Co-immunoprecipitation, ubiquitination assay, peptide disruption of protein-protein interaction, in vivo APL models Clinical cancer research High 31235507
2020 USP4 binds to, deubiquitinates, and stabilizes TWIST1 protein, promoting lung cancer stemness; silencing USP4 leads to TWIST1 degradation and loss of cancer stem cell properties, rescuable by TWIST1 re-expression. Co-immunoprecipitation, deubiquitination assay, knockdown/overexpression, stem cell assays Cancers Medium 32549341
2020 USP18 interacts with TWIST1, removes its ubiquitin chains, and stabilizes it to promote EMT and glioblastoma invasion; TWIST1 re-expression fully rescues USP18-depletion phenotypes. Co-immunoprecipitation, ubiquitination assay, shRNA knockdown, in vivo tumor model American journal of cancer research Medium 32368392
2020 CBX7 binds the E-box sequence to block TWIST1 from binding its target DNA, rendering TWIST1 transcriptionally nonfunctional in secondary ovarian cancer cells; deletion of CBX7 reactivates TWIST1-induced transcription and mesenchymal transformation. Chromatin binding assay, E-box competition assay, CBX7 knockout, in vivo tumorigenicity Oncogene Medium 32205869
2020 Mutant CFTR intrinsically triggers EMT through TWIST1; CFTR modulator drugs reverse the CF EMT phenotype by restoring functional CFTR and reducing TWIST1-mediated EMT. CFTR-mutant cell lines and native tissue, EMT marker expression, drug rescue with CFTR modulators Cell death & disease Medium 33106471
2020 G3BP2 promotes TWIST1 ubiquitination and proteasomal degradation; α-parvin binding to G3BP2 prevents this interaction, thereby stabilizing TWIST1 and promoting breast cancer metastasis. Co-immunoprecipitation, ubiquitination assay, mutagenesis of α-parvin G3BP2-binding site, in vivo tumor progression Oncogene High 30804457
2021 TWIST1 and chromatin regulators CHD7, CHD8, and WHSC1 form a TWIST1-chromatin regulatory module (TWIST1-CRM) in neural crest cells; perturbation of any core member causes abnormal NCC differentiation and craniofacial defects. TWIST1-CRM represses neural stem cell programs at low activity and commits NCCs to ectomesenchyme at high activity. BioID proximity labeling, network propagation analysis, combinatorial knockdown in cell models and mouse embryos eLife High 33554859
2022 Twist1 in macrophages directly activates galectin-3 transcription and regulates M2 macrophage polarization; Twist1 also controls macrophage chemotaxis partly through the CCL2/CCR2 axis. Macrophage-specific Twist1 ablation reduces renal fibrosis. Conditional macrophage-specific Twist1 knockout, ChIP (galectin-3 promoter), cytokine secretion assays, UUO model Cellular and molecular life sciences High 35182235
2023 TWIST1 acetylation at K73/76 determines its co-activator versus co-repressor function: non-acetylated TWIST1-K73/76 recruits NuRD complex to repress epithelial target genes, while diacetylated TWIST1-acK73/76 binds BRD8 (a TIP60-Com component) to recruit TIP60-Com and activate mesenchymal genes and MYC. Knockdown of BRD8 abolishes TWIST1/TIP60-Com interaction and reduces TWIST1-activated gene expression. Co-immunoprecipitation, ChIP-seq, acetylation-mimetic/dead mutants, BRD8 knockdown, RNA-seq EMBO reports High 37680145
2023 CDK1 phosphorylates USP29, which activates USP29's deubiquitinase activity toward TWIST1, thereby stabilizing TWIST1 and promoting EMT, chemoresistance, and metastasis in TNBC; CDK1 inhibition destabilizes TWIST1. In vitro kinase assay, ubiquitination assay, Co-immunoprecipitation, CDK1 genetic ablation, pharmacological inhibition Advanced science High 36782089
2023 USP13 directly interacts with TWIST1, cleaves K48-linked polyubiquitin chains added by FBXL14, and stabilizes TWIST1 protein; TWIST1 in turn transcriptionally represses USP13, forming a negative feedback loop. Co-immunoprecipitation, GST-pulldown, ubiquitination assay, ChIP and luciferase reporter Cellular oncology Medium 36732432
2023 FBXO3 stabilizes USP4 by disrupting the interaction between USP4 and DNPEP (aspartyl aminopeptidase), preventing DNPEP-mediated USP4 degradation; stabilized USP4 in turn deubiquitinates and stabilizes TWIST1 to promote breast cancer metastasis. PI3K-p110αH1047R facilitates FBXO3 phosphorylation and stabilization via ERK1. Co-immunoprecipitation, ubiquitination assay, FBXO3 mutagenesis (E3-dead), in vivo mouse metastasis assay PLoS biology High 38134227
2011 TWIST1 directly binds to Bmi1 promoter E-box sequences and activates Bmi1 expression, linking EMT induction to cancer stemness via chromatin remodeling. Chromatin immunoprecipitation, reporter assays, head and neck cancer patient samples Bioscience reports Medium 21919891
2011 TWIST1 directly binds E-box sequences in the promoters of Tbx20, Cdh11, Sema3C, Rab39b, and Gadd45a in developing heart valve endocardial cushion cells, regulating proliferation and migration of valve mesenchymal cells. ChIP assay, candidate gene and global gene profiling, evolutionarily conserved E-box analysis PloS one Medium 22242143
2015 TWIST1 directly binds the promoters of Cyclin E1, E2F1, and c-Myc at canonical E-box motifs to regulate cell cycle progression at G1/S, promoting keratinocyte proliferation and skin tumor initiation. ChIP, conditional Twist1 KO in keratinocytes, cell cycle analysis, Western blot Molecular carcinogenesis High 26013710
2016 TWIST1 directly binds the promoters of Ddr2, Pcolce, and Tgfbi in cranial mesoderm, and these targets regulate extracellular matrix/cell-matrix interactions required for mesenchymal maintenance. ChIP-seq in an in vitro TWIST1-dependent mesenchymal model identified genome-wide TWIST1 binding sites. ChIP-seq, ChIP-PCR on embryonic tissues, luciferase reporter assays, Twist1 conditional KO Developmental biology High 27546376
2013 TWIST1 directly binds the FoxM1 promoter at an E-box motif and recruits p300 to induce FoxM1 mRNA transcription, thereby promoting gastric cancer cell proliferation. ChIP, reporter assay, knockdown/overexpression of Twist1 and FoxM1 PloS one Medium 24204899
2020 TWIST1 drives smooth muscle cell proliferation in pulmonary hypertension by promoting proteasomal degradation of GATA-6; loss of GATA-6 reduces BMPR2 expression because GATA-6 directly binds the BMPR2 promoter. SMC-specific Twist1 deletion attenuates PH and vascular remodeling. SMC-specific Twist1 conditional KO, mass spectrometry, Co-IP, ChIP, in vitro SMC proliferation American journal of respiratory and critical care medicine High 32692930
2019 TWIST1 directly induces expression of discoidin domain receptor 2 (DDR2) in ovarian cancer cells, and DDR2 stabilizes SNAIL1 to sustain the mesenchymal phenotype and enable peritoneal metastasis. shRNA knockdown, overexpression, in vivo metastasis model, patient-derived tumor cells Oncogene Medium 29348456
2015 TWIST1 directly binds to the miR-584 genomic locus to activate its transcription (confirmed by ChIP), and miR-584 targets TUSC2 to promote resistance to apoptosis in thyroid cancer cells. ChIP, miRNome profiling, luciferase assay, overexpression/anti-miR experiments Oncotarget Medium 27661106
2008 TWIST1 expression in Th1 effector memory cells is induced by NF-κB, NFAT, and IL-12/STAT4 signaling, and TWIST1 in turn limits expression of IFN-γ, IL-2, and TNF-α to autoregulate Th1-mediated immunopathology. T cell stimulation assays, transcription factor inhibition (dominant negatives and pharmacological), adoptive transfer models of delayed-type hypersensitivity and antigen-induced arthritis The Journal of experimental medicine High 18663125
2014 TWIST1 dissemination from primary mammary epithelium requires E-cadherin; Twist1 expression induces changes in extracellular matrix and cell-matrix adhesion genes (not cell-cell adhesion genes), and E-cadherin knockdown strongly inhibits Twist1-induced single-cell dissemination. 3D mammary organoid culture, live imaging, RNA-seq transcriptional profiling, E-cadherin knockdown, conditional mouse model The Journal of cell biology High 24590176
2004 TWIST1 (H-Twist) overexpression inhibits the ARF/p53 apoptotic pathway in N-Myc-amplified neuroblastoma, enabling oncogenic cooperation between TWIST1 and N-Myc to cause cell transformation and circumvent p53-dependent apoptosis. Pangenomic cDNA microarray, functional cell transformation assays, apoptosis assays Cancer cell Medium 15607966
2018 Enhancers eTw-5, eTw-6, and eTw-7 within the TWIST1-HDAC9 locus physically interact with the Twist1 promoter (by 4C-seq) in limb bud and branchial arch; LMX1B and TFAP2 bind these enhancers to modulate TWIST1 transcription. CRISPR deletion of eTw5-7 reduces Twist1 expression and causes pre-axial polydactyly. 4C-seq, ChIP-seq (p300, H3K27ac), CRISPR/Cas9 enhancer deletion, zebrafish/mouse enhancer assays PLoS genetics High 30372441
2023 TWIST1 is highly expressed in IPF myofibroblasts with selectively increased chromatin accessibility at the TWIST1 locus; Twist1 overexpression in COL1A2-expressing fibroblasts increases collagen synthesis and upregulates fibrosis-related gene programs. Single-nucleus ATAC-seq, scRNA-seq integration, Twist1 overexpression in bleomycin-injured Cre-ER mice, RNA-seq European respiratory journal High 37142338

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 Normal and disease-related biological functions of Twist1 and underlying molecular mechanisms. Cell research 371 21876555
2010 Expression and functional significance of Twist1 in hepatocellular carcinoma: its role in vasculogenic mimicry. Hepatology (Baltimore, Md.) 281 19957372
2018 Twist1 Regulates Vimentin through Cul2 Circular RNA to Promote EMT in Hepatocellular Carcinoma. Cancer research 268 29844124
2004 Oncogenic cooperation between H-Twist and N-Myc overrides failsafe programs in cancer cells. Cancer cell 208 15607966
2014 Regulation of cell proliferation and migration by p62 through stabilization of Twist1. Proceedings of the National Academy of Sciences of the United States of America 190 24927592
2015 Different levels of Twist1 regulate skin tumor initiation, stemness, and progression. Cell stem cell 176 25575080
2005 Altered Twist1 and Hand2 dimerization is associated with Saethre-Chotzen syndrome and limb abnormalities. Nature genetics 164 15735646
2013 Twist1 induces CCL2 and recruits macrophages to promote angiogenesis. Cancer research 160 23329645
2014 Twist1-induced dissemination preserves epithelial identity and requires E-cadherin. The Journal of cell biology 156 24590176
2015 miR-186 regulation of Twist1 and ovarian cancer sensitivity to cisplatin. Oncogene 134 25867064
2016 Twist1 promotes breast cancer invasion and metastasis by silencing Foxa1 expression. Oncogene 129 27524420
2016 TWIST1 Integrates Endothelial Responses to Flow in Vascular Dysfunction and Atherosclerosis. Circulation research 122 27245171
2008 Autoregulation of Th1-mediated inflammation by twist1. The Journal of experimental medicine 94 18663125
2013 STAT3 mediates TGF-β1-induced TWIST1 expression and prostate cancer invasion. Cancer letters 92 23623921
2014 TRIM29 suppresses TWIST1 and invasive breast cancer behavior. Cancer research 83 24950909
2012 Expression of epithelial-mesenchymal transition regulators SNAI2 and TWIST1 in thyroid carcinomas. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 76 22899291
2017 A First-in-Class TWIST1 Inhibitor with Activity in Oncogene-Driven Lung Cancer. Molecular cancer research : MCR 74 28851812
2015 Complement Component 3 Is Regulated by TWIST1 and Mediates Epithelial-Mesenchymal Transition. Journal of immunology (Baltimore, Md. : 1950) 74 26718342
2014 Autophagy deficiency stabilizes TWIST1 to promote epithelial-mesenchymal transition. Autophagy 73 25126736
2014 MicroRNA-543 suppresses endometrial cancer oncogenicity via targeting FAK and TWIST1 expression. Archives of gynecology and obstetrics 64 24699721
2011 Epithelial-mesenchymal transition and cancer stemness: the Twist1-Bmi1 connection. Bioscience reports 64 21919891
2022 Twist1 regulates macrophage plasticity to promote renal fibrosis through galectin-3. Cellular and molecular life sciences : CMLS 60 35182235
2019 Up-regulation of PCOLCE by TWIST1 promotes metastasis in Osteosarcoma. Theranostics 59 31285765
2015 RNA-based TWIST1 inhibition via dendrimer complex to reduce breast cancer cell metastasis. BioMed research international 59 25759817
2008 Phosphoregulation of Twist1 provides a mechanism of cell fate control. Current medicinal chemistry 59 18855684
2011 TWIST1 is expressed in colorectal carcinomas and predicts patient survival. PloS one 58 21464926
2015 A20 suppresses hepatocellular carcinoma proliferation and metastasis through inhibition of Twist1 expression. Molecular cancer 57 26538215
2013 miR-181a-Twist1 pathway in the chemoresistance of tongue squamous cell carcinoma. Biochemical and biophysical research communications 55 24148247
2017 The Aurora-A-Twist1 axis promotes highly aggressive phenotypes in pancreatic carcinoma. Journal of cell science 52 28167680
2020 MYC and Twist1 cooperate to drive metastasis by eliciting crosstalk between cancer and innate immunity. eLife 51 31933479
2019 Targeting MUC1-C Inhibits TWIST1 Signaling in Triple-Negative Breast Cancer. Molecular cancer therapeutics 50 31308076
1998 Members of the meis1 and pbx homeodomain protein families cooperatively bind a cAMP-responsive sequence (CRS1) from bovine CYP17. The Journal of biological chemistry 50 9525891
2018 TWIST1 induces expression of discoidin domain receptor 2 to promote ovarian cancer metastasis. Oncogene 48 29348456
2013 Twist1 controls a cell-specification switch governing cell fate decisions within the cardiac neural crest. PLoS genetics 48 23555309
2013 Twist1 promotes gastric cancer cell proliferation through up-regulation of FoxM1. PloS one 47 24204899
1994 A cAMP-regulatory sequence (CRS1) of CYP17 is a cellular target for the homeodomain protein Pbx1. The Journal of biological chemistry 47 7913464
2020 Mutant CFTR Drives TWIST1 mediated epithelial-mesenchymal transition. Cell death & disease 45 33106471
2017 miR-203 Suppresses Bladder Cancer Cell Growth and Targets Twist1. Oncology research 45 28893347
2018 p53-Pirh2 Complex Promotes Twist1 Degradation and Inhibits EMT. Molecular cancer research : MCR 44 30131448
2015 SOX5 promotes epithelial-mesenchymal transition and cell invasion via regulation of Twist1 in hepatocellular carcinoma. Medical oncology (Northwood, London, England) 44 25572815
2019 CADM1 is a TWIST1-regulated suppressor of invasion and survival. Cell death & disease 43 30911007
2016 Composition of TWIST1 dimers regulates fibroblast activation and tissue fibrosis. Annals of the rheumatic diseases 43 27113414
2016 Role of Twist1 Phosphorylation in Angiogenesis and Pulmonary Fibrosis. American journal of respiratory cell and molecular biology 43 27281171
2014 TWIST1 is a direct transcriptional target of MYCN and MYC in neuroblastoma. Cancer letters 43 25475555
2010 Twist1 in human white adipose tissue and obesity. The Journal of clinical endocrinology and metabolism 42 20943789
2011 Twist1 directly regulates genes that promote cell proliferation and migration in developing heart valves. PloS one 41 22242143
2023 Phosphorylation of USP29 by CDK1 Governs TWIST1 Stability and Oncogenic Functions. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 39 36782089
2023 Molecular mechanisms of TWIST1-regulated transcription in EMT and cancer metastasis. EMBO reports 39 37680145
1997 The activity of the scs and scs' insulator elements is not dependent on chromosomal context. Molecular and cellular biology 38 8972198
2021 TWIST1 and chromatin regulatory proteins interact to guide neural crest cell differentiation. eLife 37 33554859
2020 The Deubiquitinase USP4 Stabilizes Twist1 Protein to Promote Lung Cancer Cell Stemness. Cancers 37 32549341
2013 Hypermethylation of TWIST1 and NID2 in tumor tissues and voided urine in urinary bladder cancer patients. DNA and cell biology 37 23682613
2020 USP18 deubiquitinates and stabilizes Twist1 to promote epithelial-mesenchymal transition in glioblastoma cells. American journal of cancer research 35 32368392
2024 TWIST1+FAP+ fibroblasts in the pathogenesis of intestinal fibrosis in Crohn's disease. The Journal of clinical investigation 34 39024569
2016 Transcriptional targets of TWIST1 in the cranial mesoderm regulate cell-matrix interactions and mesenchyme maintenance. Developmental biology 34 27546376
2016 DNMT3A mutation leads to leukemic extramedullary infiltration mediated by TWIST1. Journal of hematology & oncology 34 27724883
2016 miR-151-3p Targets TWIST1 to Repress Migration of Human Breast Cancer Cells. PloS one 34 27930738
2020 CBX7 binds the E-box to inhibit TWIST-1 function and inhibit tumorigenicity and metastatic potential. Oncogene 33 32205869
2023 Rab31 promotes metastasis and cisplatin resistance in stomach adenocarcinoma through Twist1-mediated EMT. Cell death & disease 32 36781842
2013 Twist1 controls lung vascular permeability and endotoxin-induced pulmonary edema by altering Tie2 expression. PloS one 31 24023872
2008 Characterization of the molecular basis of group II intron RNA recognition by CRS1-CRM domains. The Journal of biological chemistry 31 18559344
2020 TWIST1-Reprogrammed Endothelial Cell Transplantation Potentiates Neovascularization-Mediated Diabetic Wound Tissue Regeneration. Diabetes 30 32234721
2020 TWIST1 Drives Smooth Muscle Cell Proliferation in Pulmonary Hypertension via Loss of GATA-6 and BMPR2. American journal of respiratory and critical care medicine 30 32692930
2017 Intercellular Genetic Interaction Between Irf6 and Twist1 during Craniofacial Development. Scientific reports 30 28769044
2014 Craniofacial shape variation in Twist1+/- mutant mice. Anatomical record (Hoboken, N.J. : 2007) 30 24585549
2019 TRIB3 Stabilizes High TWIST1 Expression to Promote Rapid APL Progression and ATRA Resistance. Clinical cancer research : an official journal of the American Association for Cancer Research 29 31235507
2018 Unraveling the transcriptional regulation of TWIST1 in limb development. PLoS genetics 29 30372441
2016 TWIST1/miR-584/TUSC2 pathway induces resistance to apoptosis in thyroid cancer cells. Oncotarget 29 27661106
2019 The FZD7-TWIST1 axis is responsible for anoikis resistance and tumorigenesis in ovarian carcinoma. Molecular oncology 27 30548372
2016 The interplay between microRNAs and Twist1 transcription factor: a systematic review. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 27 26880587
2014 Identification of targets of Twist1 transcription factor in thyroid cancer cells. The Journal of clinical endocrinology and metabolism 27 24848707
2023 Single-nucleus chromatin accessibility identifies a critical role for TWIST1 in idiopathic pulmonary fibrosis myofibroblast activity. The European respiratory journal 25 37142338
2014 Twist1 correlates with poor differentiation and progression in gastric adenocarcinoma via elevation of FGFR2 expression. World journal of gastroenterology 24 25561797
2021 Twist1 in podocytes ameliorates podocyte injury and proteinuria by limiting CCL2-dependent macrophage infiltration. JCI insight 23 34369383
2020 Sox13 promotes hepatocellular carcinoma metastasis by transcriptionally activating Twist1. Laboratory investigation; a journal of technical methods and pathology 23 32461589
2015 Twist1 regulates keratinocyte proliferation and skin tumor promotion. Molecular carcinogenesis 23 26013710
2019 Inhibition of Heat Shock Protein 90 suppresses TWIST1 Transcription. Molecular pharmacology 22 31175180
2018 KLF11 promotes gastric cancer invasion and migration by increasing Twist1 expression. Neoplasma 22 30509092
2020 MiR-337-3p Promotes Adipocyte Browning by Inhibiting TWIST1. Cells 21 32340411
2019 TWIST1 Alleviates Hypoxia-induced Damage of Trophoblast Cells by inhibiting mitochondrial apoptosis pathway. Experimental cell research 21 31669261
2017 Aminopeptidase A initiates tumorigenesis and enhances tumor cell stemness via TWIST1 upregulation in colorectal cancer. Oncotarget 21 28177885
2015 TWIST1 and TWIST2 regulate glycogen storage and inflammatory genes in skeletal muscle. The Journal of endocrinology 21 25663706
2015 Twist1 Is Essential for Tooth Morphogenesis and Odontoblast Differentiation. The Journal of biological chemistry 21 26487719
2014 Role and mechanism of Twist1 in modulating the chemosensitivity of FaDu cells. Molecular medicine reports 21 24805866
2018 miR-16-1-3p targets TWIST1 to inhibit cell proliferation and invasion in NSCLC. Bratislavske lekarske listy 20 29405733
2023 USP13 promotes breast cancer metastasis through FBXL14-induced Twist1 ubiquitination. Cellular oncology (Dordrecht, Netherlands) 19 36732432
2023 FBXO3 stabilizes USP4 and Twist1 to promote PI3K-mediated breast cancer metastasis. PLoS biology 19 38134227
2022 TWIST1-EP300 Expedites Gastric Cancer Cell Resistance to Apatinib by Activating the Expression of COL1A2. Analytical cellular pathology (Amsterdam) 19 35242497
2022 The potential of sertoli cells (SCs) derived exosomes and its therapeutic efficacy in male reproductive disorders. Life sciences 19 36463941
2021 Obesity Inhibits Angiogenesis Through TWIST1-SLIT2 Signaling. Frontiers in cell and developmental biology 19 34660572
2020 TWIST1 upregulation affects E-cadherin expression in brain metastases. Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico 19 33006113
2019 α-Parvin promotes breast cancer progression and metastasis through interaction with G3BP2 and regulation of TWIST1 signaling. Oncogene 19 30804457
2018 The role of Twist1 in mutant huntingtin-induced transcriptional alterations and neurotoxicity. The Journal of biological chemistry 19 29891550
2018 Twist1/2 activates MMP2 expression via binding to its promoter in colorectal cancer. European review for medical and pharmacological sciences 19 30556860
2015 Over-expression of miR-10b in NPC patients: correlation with LMP1 and Twist1. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 19 25597482
2022 Norepinephrine promotes glioma cell migration through up-regulating the expression of Twist1. BMC cancer 18 35219305
2018 Disruption of TWIST1 translation by 5' UTR variants in Saethre-Chotzen syndrome. Human mutation 18 30040876
2017 Reactivation of TWIST1 contributes to Ewing sarcoma metastasis. Pediatric blood & cancer 18 28873262
2019 Twist1 Correlates With Epithelial-Mesenchymal Transition Markers Fibronectin and Vimentin in Adrenocortical Tumors. Anticancer research 17 30591455
2012 Linkage between Twist1 and Bmi1: molecular mechanism of cancer metastasis/stemness and clinical implications. Clinical and experimental pharmacology & physiology 17 21883379