Affinage

WASF3

Actin-binding protein WASF3 · UniProt Q9UPY6

Length
502 aa
Mass
55.3 kDa
Annotated
2026-04-28
61 papers in source corpus 30 papers cited in narrative 30 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

WASF3 is a WAVE/SCAR-family actin regulatory protein that functions within the pentameric WAVE Regulatory Complex (WRC; containing CYFIP1, NCKAP1, Abi, BRK1) to drive Arp2/3-dependent actin polymerization, lamellipodia formation, and cell migration downstream of RAC1 and PI3K signaling (PMID:15752430, PMID:15826941, PMID:26676744). Its activation requires tyrosine phosphorylation by c-Abl and JAK2, stabilization by HSP70 (cytoplasmic) and ATAD3A/GRP78 (mitochondrial), and transcriptional induction by HIF1A, JAK2/STAT3, and SHOX2, while its mRNA is post-transcriptionally regulated by miR-200, miR-31, and METTL3-mediated m6A modification (PMID:17623672, PMID:25823022, PMID:22315230, PMID:22581642, PMID:23677069, PMID:19801681, PMID:41127505). In cancer cells, phospho-active WASF3 promotes invasion and metastasis through NF-κB–dependent MMP-9 expression (via KISS1 suppression), ZEB1-driven EMT, YB1-mediated cancer stem cell gene activation, and β-catenin stabilization, while also forming a positive feedback loop with PI3K, TGF-β, and EGF signaling (PMID:15907837, PMID:21544801, PMID:23318438, PMID:29262622, PMID:36949468, PMID:33012785). Beyond oncogenesis, WASF3 is recruited by PCARE to the primary cilium to drive actin-dependent photoreceptor outer segment disk formation, and its overexpression disrupts mitochondrial respiratory supercomplex assembly, a mechanism linked to exercise intolerance in ME/CFS (PMID:32312818, PMID:37579159).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2005 High

    Establishing WASF3 as an actin-regulating driver of cell migration: WASF3 was shown to localize to lamellipodia, interact with PI3K-p85 to couple growth factor signaling to actin remodeling, participate in the pentameric WRC, and regulate p38 MAPK–MMP expression for invasion — defining its core cellular function.

    Evidence Co-IP, yeast two-hybrid, siRNA/shRNA KD, PI3K inhibitor, invasion assays, Matrigel, confocal microscopy in breast cancer cells

    PMID:15752430 PMID:15826941 PMID:15907837

    Open questions at the time
    • Direct interaction with Arp2/3 complex not demonstrated for WASF3 specifically
    • Relative contributions of WASF3 vs WAVE1/WAVE2 in vivo not resolved
  2. 2007 High

    Identifying c-Abl as the activating kinase and validating WASF3 as a metastasis driver in vivo: Abl-mediated tyrosine phosphorylation was shown to be required for lamellipodia formation, and stable WASF3 knockdown suppressed lung metastasis in orthotopic xenografts via p38 MAPK.

    Evidence In vitro kinase assay, site-directed mutagenesis, STI-571 inhibitor, orthotopic xenograft and tail-vein injection models

    PMID:17525277 PMID:17623672

    Open questions at the time
    • Identity of specific Abl phosphorylation sites functionally critical for metastasis not individually dissected
    • Whether Abl phosphorylation affects WRC assembly or only downstream signaling unclear
  3. 2009 High

    Revealing post-transcriptional control of WASF3: miR-200 and later miR-31 were identified as direct suppressors of WASF3 mRNA, linking WASF3 to the epithelial–mesenchymal transition regulatory circuit.

    Evidence 3′-UTR luciferase reporters, miRNA overexpression, miR-resistant WASF3 rescue constructs, invasion assays

    PMID:19801681 PMID:21105030

    Open questions at the time
    • Relative quantitative contribution of each miRNA to endogenous WASF3 levels in different tumor types not established
  4. 2011 High

    Uncovering the KISS1–NF-κB–MMP-9 axis as the effector pathway downstream of WASF3: WASF3 suppresses the metastasis suppressor KISS1, enabling NF-κB nuclear translocation and MMP-9 transcription; epistasis rescue confirmed KISS1 as the critical mediator.

    Evidence shRNA KD, oligonucleotide arrays, NF-κB luciferase reporter, nuclear fractionation, MMP-9 activity assay, KISS1 rescue

    PMID:21544801

    Open questions at the time
    • Mechanism by which WASF3 suppresses KISS1 expression not defined
    • Whether KISS1 suppression requires WRC integrity or is an independent WASF3 function unclear
  5. 2012 High

    Defining the chaperone hierarchy maintaining WASF3 protein and revealing HIF1A-driven transcriptional induction: HSP70 stabilizes WASF3 protein against proteasomal degradation while HSP90 sustains Abl to enable WASF3 phosphoactivation; separately, HIF1A binds HRE elements in the WASF3 promoter under hypoxia.

    Evidence Mass spectrometry, Co-IP, HSP90/HSP70 inhibitors, proteasome inhibitors, ChIP, luciferase reporter, shRNA KD

    PMID:22315230 PMID:22581642

    Open questions at the time
    • HSP70 binding site on WASF3 not mapped
    • Relative importance of HIF1A vs STAT3 vs other transcription factors for WASF3 expression in different contexts not compared
  6. 2013 High

    Connecting WASF3 to EMT and JAK2/STAT3 transcriptional control: WASF3 drives ZEB1 via NF-κB to suppress miR-200 and E-cadherin; JAK2/STAT3 was identified as both a transcriptional inducer and a direct phospho-activator of WASF3, and TGF-β was shown to selectively induce WASF3 in metastatic cells.

    Evidence ChIP, shRNA, dominant-negative constructs, JAK2/STAT3 inhibitors, Co-IP, 3D organotypic cultures, syngeneic mouse model

    PMID:23318438 PMID:23677069 PMID:24197660

    Open questions at the time
    • Whether JAK2 phosphorylates the same WASF3 residues as c-Abl not determined
    • TGF-β–Smad2 mechanism for WASF3 induction not fully elucidated
  7. 2015 High

    Discovering a mitochondrial pool of WASF3 stabilized by ATAD3A/GRP78 and demonstrating druggability of the WRC: ATAD3A anchors WASF3 at the mitochondrial membrane independently of HSP70; stapled peptides disrupting the WASF3-CYFIP1 interface abolished RAC1 binding and invasion.

    Evidence MS, Co-IP, mitochondria proteolysis assay, shRNA KD, structure-guided stapled peptide design, invasion assays, xenograft

    PMID:25823022 PMID:26676744

    Open questions at the time
    • Function of mitochondrial WASF3 pool beyond protein stabilization not clear at this point
    • In vivo pharmacokinetics and efficacy of stapled peptides not established
  8. 2016 High

    Placing WASF3 downstream of HER2/HER3 and validating NCKAP1 as essential for WRC integrity: HER2/HER3 heterodimer drives WASF3 phosphoactivation via JAK/STAT; disruption of the NCKAP1-CYFIP1 interface destabilized the complex and suppressed metastasis.

    Evidence Co-IP, shRNA, HER2/HER3 overexpression, small molecule (WANT3), RAC1 pulldown, spontaneous metastasis model

    PMID:26804171 PMID:27432794

    Open questions at the time
    • Structural basis of WANT3 binding not resolved
    • Whether all receptor tyrosine kinases converge on the same WASF3 phosphorylation sites unclear
  9. 2017 High

    Expanding WASF3 function to cancer stemness and RAS-PI3K-AKT signaling: WASF3 interacts with YB1 to drive its nuclear translocation and CSC gene activation; mutant RAS promotes WASF3 activation via PI3K/AKT, with AKT present in the WASF3 immunocomplex.

    Evidence Co-IP, CRISPR KO, tumorsphere assays, mass spectrometry, shRNA, invasion/metastasis assays

    PMID:28233357 PMID:29262622

    Open questions at the time
    • Whether YB1 interaction requires the WRC or occurs with free WASF3 not tested
    • Direct AKT phosphorylation of WASF3 not demonstrated
  10. 2020 High

    Revealing a non-oncogenic developmental role: PCARE recruits WASF3 to the primary cilium to drive actin-dependent ciliary tip expansion and photoreceptor outer segment disk membrane formation, establishing WASF3 in retinal biology.

    Evidence Co-IP, siRNA KD, ectopic co-expression in ciliated cells, Pcare KO mice, human retinal organoids, pharmacological actin inhibition

    PMID:32312818

    Open questions at the time
    • Whether WASF3 loss alone causes retinal dystrophy in humans not demonstrated
    • WRC requirement at the cilium not tested
  11. 2021 High

    Refining phosphorylation-dependent interactions and upstream transcriptional control: PRD phosphorylation was shown to be specifically required for WASF3-YB1 binding and CSC/EMT; SHOX2 was identified as a transcription factor that cooperates with STAT3 at the WASF3 promoter.

    Evidence Phospho-mutant PRD constructs, Co-IP, ChIP/re-ChIP, orthotopic breast tumor model, xenograft

    PMID:33594155 PMID:34465361

    Open questions at the time
    • Kinase responsible for PRD phosphorylation not identified
    • Whether SHOX2-STAT3 cooperation is tissue-specific unknown
  12. 2023 High

    Uncovering mitochondrial and metabolic consequences of WASF3: WASF3 overexpression disrupts respiratory supercomplex formation and reduces complex IV, causing exercise intolerance; elevated WASF3 was observed in ME/CFS patient muscle; phospho-active WASF3 stabilizes β-catenin in TNBC to confer chemoresistance.

    Evidence WASF3 transgenic mice, BN-PAGE supercomplex analysis, patient biopsies, CRISPR KO, phospho-mutant rescue, xenograft

    PMID:36949468 PMID:37579159

    Open questions at the time
    • Direct molecular mechanism by which WASF3 disrupts supercomplexes not identified
    • Whether WASF3-driven β-catenin stabilization requires WRC or mitochondrial localization not tested
    • Causal role of WASF3 in ME/CFS pathogenesis not established beyond association
  13. 2025 Medium

    Adding an epitranscriptomic layer: METTL3-mediated m6A modification of WASF3 mRNA enhances its translation via IGF2BP2 binding, linking RNA methylation to WASF3-driven MAPK activation.

    Evidence Co-IP, m6A modification assay, Western blotting, functional invasion assays

    PMID:41127505

    Open questions at the time
    • Independent replication in additional cancer types needed
    • Quantitative contribution of m6A to total WASF3 protein levels not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the direct mechanism by which WASF3 disrupts mitochondrial respiratory supercomplexes, the identity of the kinase(s) phosphorylating the PRD, whether WASF3 functions at the cilium through the canonical WRC, and whether WASF3 is causally sufficient for ME/CFS pathogenesis.
  • No structural model of full-length WASF3 in the WRC context
  • Mechanism of KISS1 transcriptional suppression by WASF3 undefined
  • Tissue-specific roles of WASF3 vs WAVE1/WAVE2 in vivo not systematically compared

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 4 GO:0060090 molecular adaptor activity 2
Localization
GO:0005856 cytoskeleton 3 GO:0005886 plasma membrane 3 GO:0005739 mitochondrion 2 GO:0005829 cytosol 1 GO:0005929 cilium 1
Pathway
R-HSA-162582 Signal Transduction 6 R-HSA-1643685 Disease 6 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-1266738 Developmental Biology 1 R-HSA-1430728 Metabolism 1
Partners
ABL1ATAD3ACYFIP1HSPA1ANCKAP1PCAREPIK3R1YBX1
Complex memberships
ATAD3A/GRP78-WASF3 mitochondrial complexWAVE Regulatory Complex (WRC)

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 WASF3 localizes to lamellipodia at the leading edge of migrating cells; WASF3 interacts with the PI3K regulatory subunit p85 (via WASF3 N-terminal region and p85 C-terminal SH2 domain), and PI3K activity is required for PDGF-induced WASF3-dependent lamellipodia formation and cell migration. Co-immunoprecipitation, yeast two-hybrid, RNA interference knockdown, PI3K inhibitor (LY294002), wound-closure and chemotaxis assays, confocal microscopy The Journal of biological chemistry High 15826941
2005 WASF3 knockdown reduces phospho-p38 MAPK levels and decreases expression of MMP-1, MMP-3, and MMP-9 (but not MMP-2), leading to inhibition of cell motility and invasion and increased actin stress fiber formation and focal adhesion reorganization; WAVE1 and WAVE2 expression are unaffected by WASF3 knockdown. RNA interference, Western blotting, Matrigel invasion assay, immunofluorescence Experimental cell research High 15907837
2005 WASF3 inclusion in the same pentameric protein complex as WAVE1 and WAVE2 (containing CYFIP1, NCKAP1, Abi, BRK1) was demonstrated; all three human WAVE/SCAR isoforms participate in similar protein complexes regulating actin assembly. Co-immunoprecipitation, pulldown assays BMC cell biology Medium 15752430
2005 WASF3 binds directly to LDOC1 via the verprolin homology domain; WASF3 expression induces translocation of LDOC1 from the nucleus to the cytoplasm, thereby inhibiting LDOC1-induced apoptosis and suppression of p53 stabilization. Co-immunoprecipitation, domain mapping, immunofluorescence localization, apoptosis assay Journal of biochemistry Medium 16272576
2007 c-Abl kinase phosphorylates WASF3 on four tyrosine residues upon PDGF stimulation; WASF3-Abl interaction and co-localization at the cell periphery are induced by PDGF; Abl-mediated phosphorylation of WASF3 is required for lamellipodia formation and cell migration, and is abrogated by the Abl inhibitor STI-571. Co-immunoprecipitation, in vitro kinase assay, site-directed mutagenesis (tyrosine residues), STI-571 pharmacological inhibition, immunofluorescence The Journal of biological chemistry High 17623672
2007 Stable shRNA knockdown of WASF3 in MDA-MB-231 breast cancer cells suppresses p38 MAPK activity, reduces Matrigel invasion, inhibits lung colony formation after tail-vein injection, and reduces primary tumor growth and lung metastasis in orthotopic xenograft models; dominant-negative p38 phenocopies WASF3 knockdown. shRNA stable knockdown, orthotopic xenograft, tail-vein injection metastasis model, dominant-negative p38 construct The American journal of pathology High 17525277
2009 The miR-200 family of microRNAs directly targets the 3′-UTR of WASF3 mRNA, suppressing its expression; miR-200-mediated downregulation of WASF3 reduces cancer cell invasion and induces morphological changes resembling mesenchymal-to-epithelial transition; re-expression of a miR-200-resistant WASF3 reverses these effects. 3′-UTR luciferase reporter assay, miRNA overexpression, miR-200-resistant WASF3 rescue, invasion assays The Journal of biological chemistry High 19801681
2011 miR-31 directly targets the 3′-UTR of WASF3 mRNA and suppresses its expression; loss of miR-31 leads to elevated WASF3 and increased cancer cell invasion; re-expression of miR-31-resistant WASF3 reverses miR-31-mediated invasion inhibition. 3′-UTR luciferase reporter assay, miRNA overexpression, miR-31-resistant WASF3 rescue, invasion assays International journal of cancer High 21105030
2011 WASF3 knockdown in breast cancer cells upregulates the KISS1 metastasis suppressor gene, elevates IκBα in the cytoplasm, reduces nuclear NF-κB (p65/p50), and decreases MMP-9 activity, resulting in loss of invasion; knockdown of KISS1 in WASF3-silenced cells rescues the invasion phenotype. shRNA knockdown, oligonucleotide arrays, luciferase reporter, NF-κB nuclear fractionation, MMP-9 activity assay, epistasis rescue International journal of cancer High 21544801
2012 HSP90 and HSP70 are present in the WASF3 immunocomplex in cancer cells; HSP90 inactivation does not affect WASF3 stability but prevents its Abl-mediated phosphoactivation by destabilizing Abl; HSP70 inactivation leads to WASF3 destabilization via proteasome degradation; overexpression of HSP70 in WASF3-null cells does not restore invasion. Mass spectrometry, co-immunoprecipitation, HSP90/70 inhibitors, proteasome inhibitors, Western blotting, invasion assays The Journal of biological chemistry High 22315230
2012 HIF1A binds to hypoxia response elements (HRE) in the WASF3 promoter under hypoxic conditions, increasing WASF3 transcription; hypoxia also increases WASF3 phosphorylation and cell motility; WASF3-knockdown cells show no motility response to hypoxia. ChIP assay, luciferase reporter assay, Western blotting, scratch wound assay, shRNA knockdown International journal of cancer High 22581642
2013 WASF3 overexpression increases ZEB1/2 levels, which suppress the miR-200a/200b/429 cluster on chromosome 1; this occurs through WASF3-mediated downregulation of KISS1, releasing IκBα inhibition of NF-κB, which in turn transcriptionally activates ZEB1; WASF3 knockdown reduces ZEB1, increases miR-200 and E-cadherin, and suppresses invasion. shRNA knockdown, WASF3 overexpression, NF-κB reporter, qRT-PCR for miR-200, Western blotting, invasion assays Oncogene High 23318438
2013 IL-6 activates WASF3 expression through JAK2/STAT3 signaling: STAT3 binds directly to the WASF3 promoter to increase transcription; JAK2 also directly interacts with and phosphorylates WASF3; JAK2 inhibition prevents WASF3 membrane localization; loss of STAT3 or JAK2 reduces WASF3 levels and cancer cell migration. ChIP assay, shRNA knockdown, dominant-negative constructs, pharmacological inhibitors (S3I-201, AG490), co-immunoprecipitation, Western blotting, migration assays Carcinogenesis High 23677069
2013 TGF-β selectively induces WASF3 expression in metastatic breast cancer cells via a Smad2- and β3 integrin-dependent mechanism linked to microRNA regulation; WASF3 is required for TGF-β-induced EMT, lamellipodia formation, and migration in triple-negative breast cancer cells. shRNA stable knockdown, siRNA, TGF-β stimulation, Western blotting, 3D organotypic cultures, syngeneic mouse model, Smad2 and β3 integrin inhibition Breast cancer research and treatment High 24197660
2014 Loss of WASF3 inhibits nuclear translocation of NF-κB and suppresses NF-κB target genes; conversely, WASF3 overexpression enhances NF-κB activity; this leads to decreased MMP-9 expression/activity, inhibition of invadopodia formation and ECM degradation, and sensitization to TNFα-induced apoptosis via AKT pathway inhibition. shRNA knockdown, WASF3 overexpression, NF-κB reporter assay, nuclear fractionation, invadopodia assay, gelatin degradation assay, apoptosis assay PloS one High 25329315
2015 ATAD3A (mitochondrial membrane protein) interacts with WASF3 and stabilizes it at the mitochondrial membrane, independently of HSP70-mediated cytoplasmic stabilization; GRP78 also forms a complex with WASF3 and ATAD3A; ER stress-induced GRP78 increases WASF3 protein levels; the N-terminal end of WASF3 is located within the mitochondria and interacts with the N-terminal end of ATAD3A; ATAD3A suppresses CDH1/E-cadherin through GRP78-mediated WASF3 stability. Mass spectrometry, co-immunoprecipitation, shRNA knockdown, isolated mitochondria proteolysis assay, Western blotting, xenograft model Oncogene High 25823022
2015 CYFIP1 interacts with WASF3 in a complex; knockdown of CYFIP1 destabilizes the WASF3 complex and suppresses invasion; stapled peptides (WAHM) targeting the WASF3-CYFIP1 α-helical interface disrupt the complex, suppress RAC1 binding to the complex, reduce cell motility and invasion, and decrease MMP-9 and increase KISS1 expression. Co-immunoprecipitation, shRNA knockdown, stapled peptide design using crystallographic data, cell motility/invasion assays, RAC1 pulldown Cancer research High 26676744
2016 WASF3 is present in the HER2 immunocomplex; the ability of WASF3 to promote invasion depends specifically on the HER2/HER3 heterodimer; HER2/HER3 activation facilitates WASF3 phospho-activation and transcriptional upregulation via JAK/STAT signaling; combined overexpression of HER2 and WASF3 promotes invasion and metastasis more than either alone. Co-immunoprecipitation, shRNA knockdown, HER2/HER3 overexpression, invasion assays, xenograft model Oncogene High 26804171
2016 NCKAP1 is required for stability of the WASF3 complex; silencing NCKAP1 destabilizes the complex, prevents RAC1 association with the complex, and suppresses invasion and spontaneous metastasis; a compound (WANT3) targeting the NCKAP1-CYFIP1 interface disrupts the complex and suppresses RAC1 binding and invasion. Co-immunoprecipitation, shRNA knockdown, RAC1 pulldown, spontaneous metastasis mouse model, small molecule compound Cancer research High 27432794
2017 WASF3 interacts with YB1; this interaction is required for YB1 translocation to the nucleus, where YB1 activates transcription of cancer stem cell (CSC)-specific genes; CRISPR/Cas9 knockout of WASF3 attenuates the CSC subpopulation and inhibits CSC transcription factor expression. Co-immunoprecipitation, CRISPR/Cas9 knockout, immunofluorescence of YB1 localization, qRT-PCR for CSC markers, tumorsphere assays Oncotarget High 29262622
2017 Mutant RAS-driven invasion and metastasis is dependent on WASF3 activation via PI3K and AKT; AKT is present in the WASF3 immunocomplex and its association is enhanced by mutant RAS; mutant RAS promotes dissociation of p85 from the WASF3 complex, promoting p110 (catalytic subunit) activation; ERK1/2 activation is not affected by WASF3 loss. Proteomics/mass spectrometry, co-immunoprecipitation, shRNA knockdown, invasion and metastasis assays Genes, chromosomes & cancer High 28233357
2020 PCARE (C2orf71) interacts with WASF3 and recruits it to the primary cilium; co-expression of PCARE and WASF3 in ciliated cells drives remarkable expansion of the ciliary tip via actin polymerization; this process is abrogated by siRNA knockdown of actin regulators, pharmacological inhibition of actin polymerization, or a retinal dystrophy-associated PCARE missense mutation; at the photoreceptor outer segment base, PCARE, WASF3, and actin co-localize to drive disk membrane initiation. Co-immunoprecipitation, siRNA knockdown, ectopic co-expression in ciliated cells, pharmacological actin inhibition, human retinal organoids, mouse retina immunofluorescence, Pcare knockout mice Proceedings of the National Academy of Sciences of the United States of America High 32312818
2020 WASF3 tyrosine phosphorylation downstream of TGF-β and EGF (in addition to PI3K) is required for its oncogenic activity; loss of WASF3 phosphorylation inhibits cell migration, tumorsphere growth, invasion, and tumor growth in vivo; WASF3 phosphorylation is required for activation of PI3K, TGF-β, and EGF signaling and their downstream effectors, forming a positive feedback loop. Phospho-mutant WASF3 constructs, Western blotting, migration/invasion assays, 3D tumorsphere assays, mouse breast cancer models Oncogenesis High 33012785
2021 SHOX2 directly activates WASF3 transcription; SHOX2 activates STAT3 and recruits it to the WASF3 promoter, where SHOX2 and STAT3 form a functional immunocomplex to promote WASF3 transcriptional activity; WASF3 knockdown abrogates SHOX2-induced metastasis but not SHOX2-dependent tumorigenesis. ChIP-qPCR, ChIP/re-ChIP, co-immunoprecipitation, shRNA knockdown, luciferase reporter, orthotopic breast tumor mouse model Journal of experimental & clinical cancer research High 34465361
2021 Phosphorylation of the proline-rich domain (PRD) of WASF3 is required for its interaction with YB1; loss of PRD phosphorylation inhibits WASF3-YB1 interaction, prevents YB1-mediated activation of CSC marker transcription, and inhibits EMT, migration, invasion, tumor growth, and metastasis in vivo. Phospho-mutant PRD constructs, co-immunoprecipitation, invasion/migration assays, tumorsphere assays, xenograft model Scientific reports High 33594155
2023 WASF3 overexpression disrupts mitochondrial respiratory supercomplex formation and reduces complex IV levels in skeletal muscle mitochondria, leading to exercise intolerance; ER stress induces WASF3 upregulation and similarly decreases complex IV; pharmacological inhibition of ER stress reduces WASF3 levels and improves mitochondrial function; elevated WASF3 and aberrant ER stress activation are observed in ME/CFS patient skeletal muscle biopsies. WASF3 transgenic mouse model, treadmill running assay, respiratory supercomplex analysis (BN-PAGE), Western blotting for complex IV, pharmacological ER stress inhibition, patient skeletal muscle biopsy analysis Proceedings of the National Academy of Sciences of the United States of America High 37579159
2023 WASF3 phosphorylation (phospho-active form) is required for β-catenin stabilization and activity in TNBC; dual blockade of WASF3 expression or phosphorylation combined with chemotherapy suppresses β-catenin activity and reverses chemoresistance in vitro and in vivo. CRISPR/Cas9 knockout, phospho-mutant WASF3 re-expression, Western blotting, 2D/3D growth assays, xenograft model Breast cancer research High 36949468
2012 Depletion of WASF3 in MDA-MB-231 cells results in larger and less dynamic lamellipodia; WASF3-depleted cells move more slowly but more persistently on 2D matrix and typically show only one lamellipod; however, WASF3 depletion does not affect invasiveness in 3D Matrigel or collagen invasion assays. shRNA depletion, live-cell imaging of lamellipodia dynamics, 2D migration assay, 3D Matrigel and collagen invasion assays The Biochemical journal High 22909346
2017 p63α transcriptionally upregulates Hsp70 expression via E2F1; elevated Hsp70 promotes bladder cancer invasion through the Hsp70/WASF3/MMP-9 axis; E2F1 mediates p63α-induced Hsp70 transcription. Western blotting, shRNA knockdown, invasion assays, reporter assay The Journal of biological chemistry Medium 28794159
2025 METTL3 interacts with WASF3 and mediates m6A modification of WASF3 mRNA; IGF2BP2 binds the m6A site in the WASF3 3′-UTR to enhance WASF3 translation; highly expressed WASF3 activates MAPK signaling by interacting with phosphorylated p38; removal of m6A modification of WASF3 mRNA inhibits WASF3 expression and abolishes its interaction with p-p38. Co-immunoprecipitation (METTL3-WASF3, WASF3-p-p38), m6A modification assay, Western blotting, qPCR, functional invasion assays MedComm Medium 41127505

Source papers

Stage 0 corpus · 61 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 Down-regulation of WAVE3, a metastasis promoter gene, inhibits invasion and metastasis of breast cancer cells. The American journal of pathology 109 17525277
2009 The miR200 family of microRNAs regulates WAVE3-dependent cancer cell invasion. The Journal of biological chemistry 103 19801681
2005 WAVE3 promotes cell motility and invasion through the regulation of MMP-1, MMP-3, and MMP-9 expression. Experimental cell research 95 15907837
2005 WAVE3-mediated cell migration and lamellipodia formation are regulated downstream of phosphatidylinositol 3-kinase. The Journal of biological chemistry 88 15826941
2015 Mitochondrial ATAD3A combines with GRP78 to regulate the WASF3 metastasis-promoting protein. Oncogene 82 25823022
2007 c-Abl-mediated phosphorylation of WAVE3 is required for lamellipodia formation and cell migration. The Journal of biological chemistry 81 17623672
2011 WAVE3, an actin remodeling protein, is regulated by the metastasis suppressor microRNA, miR-31, during the invasion-metastasis cascade. International journal of cancer 79 21105030
2012 HSP90 and HSP70 proteins are essential for stabilization and activation of WASF3 metastasis-promoting protein. The Journal of biological chemistry 76 22315230
2013 WASF3 regulates miR-200 inactivation by ZEB1 through suppression of KISS1 leading to increased invasiveness in breast cancer cells. Oncogene 73 23318438
2016 The WASF3-NCKAP1-CYFIP1 Complex Is Essential for Breast Cancer Metastasis. Cancer research 64 27432794
2014 MicroRNA-217 regulates WASF3 expression and suppresses tumor growth and metastasis in osteosarcoma. PloS one 61 25289936
2005 Inclusion of Scar/WAVE3 in a similar complex to Scar/WAVE1 and 2. BMC cell biology 61 15752430
2020 PCARE and WASF3 regulate ciliary F-actin assembly that is required for the initiation of photoreceptor outer segment disk formation. Proceedings of the National Academy of Sciences of the United States of America 60 32312818
2010 Inactivation of the WASF3 gene in prostate cancer cells leads to suppression of tumorigenicity and metastases. British journal of cancer 60 20717117
2013 Upregulated WAVE3 expression is essential for TGF-β-mediated EMT and metastasis of triple-negative breast cancer cells. Breast cancer research and treatment 54 24197660
2011 Functional interrelationship between the WASF3 and KISS1 metastasis-associated genes in breast cancer cells. International journal of cancer 53 21544801
2015 Targeting the WASF3-CYFIP1 Complex Using Stapled Peptides Suppresses Cancer Cell Invasion. Cancer research 52 26676744
2002 WAVE3, an actin-polymerization gene, is truncated and inactivated as a result of a constitutional t(1;13)(q21;q12) chromosome translocation in a patient with ganglioneuroblastoma. Oncogene 50 12185600
2009 WAVE3 is associated with invasiveness in prostate cancer cells. Urologic oncology 43 19395286
2013 Critical role of the WASF3 gene in JAK2/STAT3 regulation of cancer cell motility. Carcinogenesis 41 23677069
2020 MicroRNA-93 targets WASF3 and functions as a metastasis suppressor in breast cancer. Cancer science 36 32307765
2016 miR-218 Inhibits Proliferation, Migration, and EMT of Gastric Cancer Cells by Targeting WASF3. Oncology research 35 27642088
2012 HIF1A induces expression of the WASF3 metastasis-associated gene under hypoxic conditions. International journal of cancer 31 22581642
2020 Asiatic Acid Interferes with Invasion and Proliferation of Breast Cancer Cells by Inhibiting WAVE3 Activation through PI3K/AKT Signaling Pathway. BioMed research international 30 32104680
2017 The WAVE3-YB1 interaction regulates cancer stem cells activity in breast cancer. Oncotarget 30 29262622
2012 Expression of MMP-9 and WAVE3 in colorectal cancer and its relationship to clinicopathological features. Journal of cancer research and clinical oncology 30 22806308
2021 SHOX2 cooperates with STAT3 to promote breast cancer metastasis through the transcriptional activation of WASF3. Journal of experimental & clinical cancer research : CR 25 34465361
2012 Surfing the big WAVE: Insights into the role of WAVE3 as a driving force in cancer progression and metastasis. Seminars in cell & developmental biology 25 23116924
2023 WASF3 disrupts mitochondrial respiration and may mediate exercise intolerance in myalgic encephalomyelitis/chronic fatigue syndrome. Proceedings of the National Academy of Sciences of the United States of America 24 37579159
2017 p63α protein up-regulates heat shock protein 70 expression via E2F1 transcription factor 1, promoting Wasf3/Wave3/MMP9 signaling and bladder cancer invasion. The Journal of biological chemistry 23 28794159
2017 TLR5/7-mediated PI3K activation triggers epithelial-mesenchymal transition of ovarian cancer cells through WAVE3-dependent mesothelin or OCT4/SOX2 expression. Oncology reports 23 28901470
2014 WAVE3-NFκB interplay is essential for the survival and invasion of cancer cells. PloS one 23 25329315
2016 WASF3 provides the conduit to facilitate invasion and metastasis in breast cancer cells through HER2/HER3 signaling. Oncogene 22 26804171
2018 WAVE3 promotes proliferation, migration and invasion via the AKT pathway in pancreatic cancer. International journal of oncology 20 29845225
2022 Targeting the WASF3 complex to suppress metastasis. Pharmacological research 18 35691539
2015 Loss of WAVE3 sensitizes triple-negative breast cancers to chemotherapeutics by inhibiting the STAT-HIF-1α-mediated angiogenesis. JAK-STAT 18 26413422
2005 WAVE3 functions as a negative regulator of LDOC1. Journal of biochemistry 18 16272576
2021 Targeting WASF3 Signaling in Metastatic Cancer. International journal of molecular sciences 15 33467681
2020 WAVE3 phosphorylation regulates the interplay between PI3K, TGF-β, and EGF signaling pathways in breast cancer. Oncogenesis 15 33012785
2017 High WAVE3 expression correlates with proliferation, migration and invasion in human ovarian cancer. Oncotarget 15 28476025
2016 WAVE3 Induces EMT and Promotes Migration and Invasion in Intrahepatic Cholangiocarcinoma. Digestive diseases and sciences 15 26971088
2015 Genes for spinocerebellar ataxia with blindness and deafness (SCABD/SCAR3, MIM# 271250 and SCABD2). European journal of human genetics : EJHG 15 26669662
2014 WAVE3 promotes epithelial-mesenchymal transition of gastric cancer through upregulation of Snail. Cancer gene therapy 14 25378074
2012 Scar/WAVE3 contributes to motility and plasticity of lamellipodial dynamics but not invasion in three dimensions. The Biochemical journal 14 22909346
2019 Wasf3 Deficiency Reveals Involvement in Metastasis in a Mouse Model of Breast Cancer. The American journal of pathology 13 31542393
2023 The WAVE3/β-catenin oncogenic signaling regulates chemoresistance in triple negative breast cancer. Breast cancer research : BCR 12 36949468
2021 Phosphorylation of the proline-rich domain of WAVE3 drives its oncogenic activity in breast cancer. Scientific reports 12 33594155
2020 WASF3 Knockdown Sensitizes Gastric Cancer Cells to Oxaliplatin by Inhibiting ATG12-Mediated Autophagy. The American journal of the medical sciences 12 32359534
2015 Knockdown of WAVE3 impairs HGF induced migration and invasion of prostate cancer cells. Cancer cell international 10 26052252
2020 Elucidating the molecular signaling pathways of WAVE3. Annals of translational medicine 9 32793744
2022 In Silico Optimized Stapled Peptides Targeting WASF3 in Breast Cancer. ACS medicinal chemistry letters 7 35450347
2014 MiR-200b modulates the properties of human monocyte-derived dendritic cells by targeting WASF3. Life sciences 6 25510861
2023 WASF3 overexpression affects the expression of circular RNA hsa-circ-0100153, which promotes breast cancer progression by sponging hsa-miR-31, hsa-miR-767-3p, and hsa-miR-935. Heliyon 5 38125536
2017 Promotion of invasion by mutant RAS is dependent on activation of the WASF3 metastasis promoter gene. Genes, chromosomes & cancer 5 28233357
2021 Fuzheng Yiliu Formula Regulates Tumor Invasion and Metastasis through Inhibition of WAVE3 Expression. Evidence-based complementary and alternative medicine : eCAM 4 33854560
2020 WAVE3 upregulation in esophageal squamous cell carcinoma and its effect on the migration of human esophageal cancer cell lines in vitro. Molecular medicine reports 4 32377706
2024 Role of WAVE3 as an actin binding protein in the pathology of triple negative breast cancer. Cytoskeleton (Hoboken, N.J.) 2 39021344
2023 Identification of small molecules that suppress cell invasion and metastasis promoted by WASF3 activation. Heliyon 2 37867831
2023 WAVE3 Facilitates the Tumorigenesis and Metastasis of Tongue Squamous Cell Carcinoma via EMT. Applied biochemistry and biotechnology 2 37947948
2025 RNA m6A Methylation Promotes Tumor Development and WASF3 Translation in Esophageal Squamous Cell Carcinoma. MedComm 1 41127505
2024 PSIP1 promotes gefitinib resistance in lung adenocarcinoma by inducing the expression of WASF3 and its downstream ITGB3/AKT signaling. Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico 1 39080187