Affinage

Showing BCAR3 — NSP2 is a alias.

BCAR3

Breast cancer anti-estrogen resistance protein 3 · UniProt O75815

Length
825 aa
Mass
92.6 kDa
Annotated
2026-06-09
79 papers in source corpus 26 papers cited in narrative 26 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

BCAR3 (AND-34) is a cytoplasmic SH2- and Cdc25-like GEF-domain adaptor that couples integrin and growth-factor signaling to Rho-family GTPase activation and cytoskeletal remodeling, and was originally isolated as a gain-of-function inducer of antiestrogen (tamoxifen) resistance in breast cancer cells (PMID:9582273, PMID:15671247). Its C-terminal GEF domain binds the focal adhesion proteins p130Cas/BCAR1 and HEF1/NEDD9 and exhibits exchange activity toward RalA, Rap1A, and R-Ras, while p130Cas binding to the GEF domain negatively regulates this activity (PMID:10438950, PMID:10896938, PMID:12517963); structural analysis places the Cas-family binding site at a position analogous to the allosteric regulatory site of SOS (PMID:19103205). Functionally, BCAR3 forms a co-regulatory positive-feedback circuit with Cas at integrin adhesions—Cas recruits BCAR3, and BCAR3 in turn promotes Cas tyrosine and serine phosphorylation, augments the c-Src SH3 interaction with Cas, and drives Rac1 activation, lamellipodia dynamics, and adhesion turnover, with its own activity gated by Tyr117 phosphorylation that targets it for ubiquitin-proteasome degradation (PMID:19940159, PMID:19454314, PMID:22711540, PMID:34169835). BCAR3 sets the Rac1/RhoA balance toward protrusive, migratory behavior (PMID:23762409), and its SH2 domain binds PTPα phospho-Tyr789 to localize the BCAR3–Cas complex to adhesions and direct Src-mediated Cas phosphorylation (PMID:22801373). Downstream, BCAR3 engages a PI3K→Rac1→PAK1→cyclin D1 axis and ERK1/2 to confer ER-independent antiestrogen resistance, the latter dependent on its physical interaction with BCAR1 (PMID:14583477, PMID:15671247, PMID:24584939). Genetic loss of BCAR3 in mice causes posterior lens rupture/extrusion cataracts with reduced Akt and Cas phosphorylation, establishing a requirement for BCAR3 in focal adhesion signaling that maintains lens epithelial integrity (PMID:19365570, PMID:27364350). Beyond these roles, BCAR3 mediates EGF- and insulin-stimulated cell cycle progression (PMID:18722344, PMID:24216110) and has been implicated in TGF-β/SMAD- and PI3K/AKT-driven programs underlying fibrosis and therapy resistance in several cancers (PMID:38414524, PMID:40935299, PMID:34765292, PMID:41595187).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1998 High

    Established BCAR3 as a causal driver of antiestrogen resistance, answering whether a single locus could confer tamoxifen escape in breast cancer cells.

    Evidence Retrovirus-mediated insertional mutagenesis with cell fusion and cDNA transfection in ZR-75-1 and MCF-7 cells

    PMID:9582273

    Open questions at the time
    • No mechanism or domain function defined at this stage
    • No endogenous partners identified
  2. 1999 Medium

    Defined the modular architecture (N-terminal SH2, C-terminal GEF-like domain) and first linked BCAR3 to adhesion signaling via p130Cas, addressing how the protein might transduce signals.

    Evidence Sequence analysis, co-IP, and tyrosine phosphorylation assays in NIH3T3 fibroblasts

    PMID:10438950

    Open questions at the time
    • GEF substrates untested
    • Functional consequence of Cas binding unknown
  3. 2000 High

    Demonstrated BCAR3 GEF activity toward RalA, Rap1A, and R-Ras and mapped p130Cas binding to the GEF domain, while showing Cas negatively regulates exchange activity—revealing a built-in regulatory logic.

    Evidence Cellular GEF activation assays and binding-domain mutant co-IPs with overexpression

    PMID:10896938

    Open questions at the time
    • No in vitro reconstitution of intrinsic exchange activity
    • Physiological GTPase target context not resolved
  4. 2003 High

    Connected BCAR3 to Rho-family (Cdc42/Rac) activation, PAK1, and cyclin D1 transcription, and showed synergy with p130Cas in Src activation and migration—mechanistically explaining its proliferative and motility effects.

    Evidence GTPase and PAK1 kinase assays, cyclin D1 reporter with dominant-negatives, Src kinase and migration assays in epithelial cells

    PMID:12517963 PMID:12740391 PMID:14583477

    Open questions at the time
    • Cell-type-specific GTPase selectivity not reconciled
    • Direct vs indirect GEF action on Rac/Cdc42 unresolved
  5. 2005 High

    Showed both SH2 and GEF domains are required for Rac activation and resistance, and placed PI3K→Akt upstream of Rac in an ER-independent resistance pathway.

    Evidence Domain mutants, PI3K/Akt assays, Rac assays, and pharmacological inhibition (LY294002, NSC23766) in stable transfectants

    PMID:15671247

    Open questions at the time
    • How SH2 and GEF domains cooperate mechanistically not defined
    • Direct PI3K-activating event not identified
  6. 2008 Medium

    Provided structural insight that the Cas-binding site lies at a SOS-like allosteric position, framing how Cas-family binding could modulate GEF output.

    Evidence SAXS and structural modeling of the BCAR3 GEF and HEF1 binding domains

    PMID:19103205

    Open questions at the time
    • Allosteric modulation not confirmed by in vitro GEF reconstitution
    • No high-resolution complex structure
  7. 2008 Medium

    Linked the BCAR3 SH2 domain to activated EGFR and showed BCAR3 is required for EGF-induced DNA synthesis, extending its role to growth-factor mitogenic signaling.

    Evidence Co-IP and microinjection of antibody/siRNA/plasmid with thymidine incorporation in MCF-12A cells

    PMID:18722344

    Open questions at the time
    • Single-lab microinjection approach
    • Direct EGFR phosphosite for SH2 binding not mapped
  8. 2009 High

    Established BCAR3 control over the Src–Cas association in endogenous cells and identified BCAR3-driven adhesion-dependent serine phosphorylation of specific p130Cas sites, defining how BCAR3 shapes Cas signaling quality.

    Evidence Gain/loss-of-function, Src kinase and adhesion assays, and mass-spectrometry phosphosite mapping with domain-swap chimeras in breast cancer cells

    PMID:19454314 PMID:19940159

    Open questions at the time
    • Kinase responsible for Cas serine phosphorylation not identified
    • Functional consequence of each phosphosite unresolved
  9. 2009 High

    Placed BCAR3 in a defined Pyk2/p130Cas→BCAR3→Rap1 axis downstream of endothelin-1 in mesangial cells, providing receptor-level epistasis.

    Evidence siRNA, dominant-interfering Pyk2, GTP-loading assays, and co-IP in glomerular mesangial cells

    PMID:19086031

    Open questions at the time
    • Tissue specificity of Rap1 selectivity not generalized
    • Downstream effectors of Rap1 here undefined
  10. 2009 High

    Defined an in vivo requirement for BCAR3 in lens epithelial integrity through Akt and Cas signaling, moving beyond cell-line phenotypes.

    Evidence Knockout mice with histopathology and Western blotting of Akt and p130Cas phosphorylation

    PMID:19365570

    Open questions at the time
    • Cell-autonomous mechanism of lens rupture not fully dissected
    • Other tissue phenotypes not surveyed
  11. 2011 High

    Dissected which functions require physical BCAR3–p130Cas complex formation, showing complex formation is dispensable for resistance/Rac but required for optimal motility and (via other Cas members) lamellipodia.

    Evidence R743A point mutant in p130Cas-null MEFs with Rac, motility, lamellipodia, and resistance assays

    PMID:21262352

    Open questions at the time
    • Identity of the alternative Cas-family partner driving motility not pinned down
    • Cas-independent signaling route undefined
  12. 2012 High

    Explained mechanistically how BCAR3 enhances Src–Cas signaling, by augmenting c-Src SH3 binding to an RPLPSPP motif in the Cas SBD, and identified PTPα pTyr789 as the first cellular SH2 ligand recruiting the complex to adhesions.

    Evidence GST pulldowns, co-IP, mutagenesis (R743A, RPLPSPP, Y789F), and PTPα-null cell reconstitution with co-localization

    PMID:22711540 PMID:22801373

    Open questions at the time
    • Whether additional SH2 ligands operate in other contexts unknown
    • Stoichiometry of the PTPα–BCAR3–Cas–Src assembly unresolved
  13. 2013 High

    Established BCAR3 as a positive regulator of cytoskeletal remodeling by setting the Rac1/RhoA balance toward protrusion and adhesion disassembly in invasive cells.

    Evidence siRNA, Rac1/RhoA activity assays, MLC phosphorylation, and ROCK inhibition with focal adhesion imaging

    PMID:23762409

    Open questions at the time
    • Direct GEF/GAP intermediaries controlling the balance not defined
    • In vivo invasion relevance not tested here
  14. 2013 Medium

    Extended BCAR3's mitogenic role to insulin signaling, showing SH2-dependent ERK activation and DNA synthesis with selectivity over IGF-1 and over GLUT4 translocation.

    Evidence Microinjection loss-of-function with ERK, DNA synthesis, ruffling, and GLUT4 assays in MCF-12A cells

    PMID:24216110

    Open questions at the time
    • Single-lab microinjection methodology
    • Receptor phosphosite engaged by SH2 not mapped
  15. 2014 High

    Identified ERK1/2 as a key effector downstream of the BCAR1–BCAR3 complex required for antiestrogen resistance, refining the resistance mechanism.

    Evidence Structure-based interaction mutants, co-IP, ERK pathway analysis, and PEA15-mediated inhibition with resistance assays in MCF7 cells

    PMID:24584939

    Open questions at the time
    • How the complex links to ERK activation mechanistically unresolved
    • Reconciliation with Cas-independent resistance (idx 12) not addressed
  16. 2021 High

    Integrated BCAR3 and Cas into a co-regulatory positive-feedback circuit and revealed Tyr117-gated proteasomal degradation as a negative-feedback brake, providing a unified dynamic model at adhesions.

    Evidence Live-cell imaging, FRAP, Y117 and SH2 mutagenesis, proteasome inhibition, and Cas-knockout cells

    PMID:34169835

    Open questions at the time
    • Kinase phosphorylating Tyr117 not identified
    • E3 ligase mediating degradation unknown
  17. 2026 Medium

    Broadened BCAR3's pathological roles into fibrosis and additional cancers via TGF-β/SMAD and PI3K/AKT/mTOR programs, indicating context-dependent signaling beyond the Cas/Src axis.

    Evidence siRNA/shRNA knockdown, in vivo fibrosis and tumor models, pathway Western blots, and pharmacological rescue across macrophage, fibroblast, HNSCC, TNBC/MET, and thyroid systems

    PMID:34765292 PMID:38414524 PMID:40935299 PMID:41595187

    Open questions at the time
    • Whether these effects use the Cas/GEF machinery or distinct adaptors unclear
    • Direct molecular link between BCAR3 and SMAD phosphorylation not established
    • Single-lab studies per disease context

Open questions

Synthesis pass · forward-looking unresolved questions
  • How BCAR3 intrinsic GEF activity is biochemically activated and regulated by Cas-family allostery, and which kinase/E3 ligase pair controls its Tyr117-dependent turnover, remain unresolved.
  • No in vitro reconstitution of regulated GEF activity
  • Tyr117 kinase and degradation E3 ligase unidentified
  • Mechanistic basis for context-specific TGF-β/SMAD coupling unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 4 GO:0098772 molecular function regulator activity 3
Localization
GO:0005829 cytosol 2 GO:0005856 cytoskeleton 2 GO:0005886 plasma membrane 2
Pathway
R-HSA-1474244 Extracellular matrix organization 3 R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 3
Partners
BCAR1CRKEGFRMETNEDD9PTK2BPTPRASRC
Complex memberships
BCAR3-HEF1/NEDD9 complexBCAR3-p130Cas/BCAR1 complexPTPalpha-BCAR3-Cas-Src complex

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 BCAR3 was identified as a novel SH2 domain-containing protein; retrovirus-mediated insertional mutagenesis revealed that transfer of the BCAR3 locus by cell fusion or transfection of BCAR3 cDNA into ZR-75-1 and MCF-7 breast cancer cells induces antiestrogen (tamoxifen) resistance. Retrovirus-mediated insertional mutagenesis, cell fusion, cDNA transfection The EMBO journal High 9582273
1999 AND-34/BCAR3 contains an N-terminal SH2 domain and a C-terminal GDP-exchange factor (GEF)-like domain; it undergoes tyrosine phosphorylation upon serum stimulation or cell adhesion to fibronectin/poly-L-lysine, and co-precipitates with the focal adhesion protein p130Cas (as well as 95- and 125-kDa tyrosine-phosphorylated proteins) in NIH3T3 fibroblasts. Co-immunoprecipitation, tyrosine phosphorylation assay, sequence analysis, Western blotting Journal of immunology Medium 10438950
2000 AND-34/BCAR3 displays GEF activity on RalA, Rap1A, and R-Ras (but not Ha-Ras) GTPases in cells. Efficient binding of AND-34 to p130Cas requires both the Src-binding domain and a flanking C-terminal region of p130Cas. The AND-34 GEF domain contains the p130Cas-binding site. Overexpression of p130Cas (but not a mutant unable to bind AND-34) inhibits AND-34's Ral GEF activity, indicating p130Cas negatively regulates AND-34 GEF function. GEF activity assay in cells (RalA/Rap1A/R-Ras activation), co-immunoprecipitation with binding-domain mutants, overexpression The Journal of biological chemistry High 10896938
2003 AND-34/BCAR3 overexpression activates Rho-family GTPases Cdc42 and Rac in epithelial cells; BCAR3 overexpression induces F-actin redistribution, augments PAK1 autophosphorylation and kinase activity, and activates the cyclin D1 promoter (proximal 163 bp) via a Rac1- and PAK1-dependent pathway, conferring antiestrogen resistance. GTPase activation assays, F-actin staining, PAK1 kinase assay, cyclin D1 promoter-luciferase reporter, dominant-negative Rac1/PAK1, stable transfection Cancer research High 14583477
2003 AND-34/BCAR3 functions synergistically with p130Cas to enhance c-Src kinase activity and promote cell migration; the C-terminal GEF domain of AND-34 and activity of its target Rap1 contribute to these events. AND-34 overexpression redistributes p130Cas from focal adhesions to lamellipodia at the leading edge. Co-immunoprecipitation, Src kinase assay, cell migration assay, immunofluorescence localization, Rap1 activity assay The Journal of biological chemistry High 12740391
2003 AND-34/BCAR3 is expressed in splenic B cells and associates with both p130Cas and HEF1 via its GEF domain binding to the HEF1 C-terminus. Overexpression in B cell lines specifically activates Cdc42 (but not Rac, Rho, RalA, or Rap1), induces PAK1 activation, and inhibits SDF-1α-induced B cell polarization. Co-immunoprecipitation, GTPase activation assays, PAK1 kinase assay, morphology (actin staining), functional polarization assay Journal of immunology Medium 12517963
2005 Both the GEF-like domain and the SH2 domain of AND-34/BCAR3 are required for Rac activation and for conferring resistance to the ER antagonist ICI 182,780. BCAR3 overexpression increases PI3K activity and augments Akt Ser473 phosphorylation/kinase activity; PI3K inhibition (LY294002 or dominant-negative p85) blocks BCAR3-mediated Rac and Akt activation. BCAR3-induced antiestrogen resistance is ER-alpha-independent. Rac inhibitor NSC23766 abrogates resistance. Domain-deletion/mutation analysis, PI3K activity assay, Akt phosphorylation/kinase assay, Rac activation assay, pharmacological inhibition, stable transfection Molecular cancer research High 15671247
2008 Structural analysis (SAXS) revealed that the NSP-binding domain of HEF1 forms a four-helix bundle, and the Cas-binding domain of BCAR3 adopts a Cdc25-like GEF fold. HEF1 binds very tightly to a site on BCAR3 that is remote from the putative GTPase-binding site of the GEF domain but analogous to an allosteric regulatory site in SOS, suggesting that Cas family binding may allosterically modulate BCAR3 GEF activity. Small-angle X-ray scattering (SAXS), structural modeling, binding analysis Journal of molecular biology Medium 19103205
2009 BCAR3 regulates c-Src kinase activity and the Src-p130Cas interaction in endogenous breast cancer cells. Using gain- and loss-of-function approaches, BCAR3 was shown to control both the quantity and quality of the Src-Cas association, and the coordinated activity of BCAR3/Cas/Src contributes to breast cancer cell adhesion signaling and spreading. Gain- and loss-of-function (overexpression and siRNA knockdown), co-immunoprecipitation, Src kinase assay, cell adhesion/spreading assay The Journal of biological chemistry High 19940159
2009 Pyk2 activation by endothelin-1 in glomerular mesangial cells leads to p130Cas phosphorylation and enhanced p130Cas-BCAR3 complex formation; BCAR3 then activates Rap1 (but not RhoA or Ras). siRNA knockdown of BCAR3 significantly decreases ET-1-induced Rap1 activation, placing BCAR3 downstream of Pyk2/p130Cas and upstream of Rap1 in this signaling axis. siRNA knockdown, dominant-interfering Pyk2 (CRNK), GTP-loading (Rap1, RhoA) assay, co-immunoprecipitation, adenovirus-mediated gene transfer Journal of cellular physiology High 19086031
2009 BCAR3 overexpression in breast cancer cells induces adhesion-dependent serine phosphorylation of p130Cas (at Ser139, Ser437, Ser639 identified by mass spectrometry). BCAR3 knockdown abolishes this phosphorylation, alters p130Cas localization, and converts MDA-231 growth to a cohesive epithelioid pattern lacking cellular projections. The BCAR3 serine/proline-rich domain is necessary for this p130Cas serine phosphorylation. Mass spectrometry phospho-site identification, phospho-amino acid analysis, inducible shRNA knockdown, immunofluorescence, domain-swap chimeras Cellular signalling High 19454314
2009 Loss of AND-34/BCAR3 in knockout mice causes posterior lens rupture beginning at ~3 weeks of age. Akt Ser473 phosphorylation and basal p130Cas phosphorylation are markedly reduced in BCAR3-null lens epithelial cells, demonstrating that BCAR3 is required for Akt and focal adhesion signaling in lens epithelium to maintain structural integrity. Homologous recombination knockout mice, histopathology, Western blotting (Akt phosphorylation, p130Cas phosphorylation), in situ hybridization Molecular vision High 19365570
2011 Using the p130Cas-binding point mutant R743A BCAR3, BCAR3-p130Cas complex formation was shown to be dispensable for BCAR3-mediated antiestrogen resistance, Rac activation, and epithelial cell discohesion, but required for optimal cell motility. While BCAR3 can signal independently of p130Cas for most functions, complex formation with other CAS family members (not p130Cas per se) is required for lamellipodia formation and motility in p130Cas-null MEFs. Point-mutant (R743A) overexpression, p130Cas-null MEFs, Rac activation assay, cell motility assay, lamellipodia formation assay, antiestrogen resistance assay Cellular signalling High 21262352
2012 BCAR3 augments the binding of the c-Src SH3 domain to p130Cas via an RPLPSPP motif in the p130Cas Src-binding domain (SBD), in a manner dependent on the BCAR3-p130Cas complex. BCAR3-induced tyrosine phosphorylation of the p130Cas substrate domain (Src-dependent) is reduced by the R743A mutation blocking BCAR3-p130Cas association. Immunofluorescence shows BCAR3 co-localizes with p130Cas and Src. GST pulldown, co-immunoprecipitation, site-directed mutagenesis (R743A BCAR3, RPLPSPP motif), immunofluorescence co-localization The Journal of biological chemistry High 22711540
2012 PTPα phospho-Tyr789 serves as the first identified cellular ligand for the BCAR3 SH2 domain, recruiting the BCAR3-Cas complex to integrin-mediated focal adhesions. In PTPα-null cells, reconstitution with wild-type PTPα (but not Y789F mutant) restores PTPα and Cas localization to adhesions and Src-mediated Cas phosphorylation, defining a PTPα→BCAR3→Cas→Src signaling axis at adhesions. PTPα-null cell reconstitution, SH2 domain binding assay, immunofluorescence/co-localization, phospho-specific antibodies, mutagenesis (Y789F) Molecular and cellular biology High 22801373
2013 In invasive breast cancer cells, BCAR3 is necessary for membrane protrusiveness, Rac1 activity, and adhesion disassembly. BCAR3 depletion shifts the Rac1/RhoA balance toward RhoA, leading to increased ROCK-mediated myosin light chain II phosphorylation and formation of large ROCK/mDia1-dependent focal adhesions, establishing BCAR3 as a positive regulator of cytoskeletal remodeling through Rac1/RhoA balance. siRNA knockdown (loss-of-function), Rac1 and RhoA activity assays, myosin light chain phosphorylation measurement, ROCK inhibitor, focal adhesion analysis by immunofluorescence PloS one High 23762409
2014 BCAR3-induced antiestrogen resistance in MCF7 cells critically depends on its physical interaction with BCAR1/p130CAS (shown using structure-based interaction mutants). BCAR3 binding to BCAR1 increases phospho-BCAR1 levels. BCAR1/BCAR3 co-overexpression correlates with increased ERK1/2 activity, and inhibition of ERK1/2 via PEA15 overexpression negates resistance, revealing ERK1/2 as a key effector downstream of the BCAR1-BCAR3 complex. Structure-based interaction mutants, co-immunoprecipitation, phosphoprotein detection, ERK1/2 kinase pathway analysis, PEA15 overexpression, antiestrogen resistance assay The Journal of biological chemistry High 24584939
2008 BCAR3 SH2 domain directly associates with activated EGF receptor and Cas in MCF-12A cells; microinjection of anti-BCAR3 antibody or BCAR3 siRNA inhibits EGF-induced DNA synthesis, and overexpression of BCAR3 alone induces DNA synthesis, placing BCAR3 as a positive mediator of EGF mitogenic signaling and cell cycle progression. Co-immunoprecipitation, microinjection of antibody/siRNA/expression plasmid, DNA synthesis assay ([3H]thymidine incorporation) Biochemical and biophysical research communications Medium 18722344
2021 BCAR3 localizes to integrin adhesions in a Cas-dependent manner; in return, Cas phosphorylation, lamellipodia dynamics, and cell migration require the BCAR3 SH2 domain and BCAR3 Tyr117 phosphorylation. Tyr117 phosphorylation also targets BCAR3 for degradation by the ubiquitin-proteasome system, creating a regulatory negative-feedback loop. This places BCAR3 and Cas in a co-regulatory positive-feedback circuit at adhesions. Live-cell imaging, FRAP, phospho-site mutagenesis (Y117), proteasome inhibitor experiments, Cas knockout cells, site-directed mutagenesis of SH2 domain eLife High 34169835
2013 BCAR3 mediates ERK activation and DNA synthesis in response to insulin (but not IGF-1) in MCF-12A cells via its SH2 domain; BCAR3 inhibition suppresses insulin-induced membrane ruffling but not GLUT4 translocation, defining a specific role for BCAR3 in insulin-stimulated cell cycle progression and cytoskeletal reorganization. Microinjection of inhibitory antibody/siRNA, ERK activation assay, DNA synthesis assay, GLUT4 translocation assay, SH2 domain blocking Biochemical and biophysical research communications Medium 24216110
2024 BCAR3 expression in macrophages is regulated by Stat6, while in fibroblasts it is regulated by TGFβR1/Smad3. BCAR3 amplifies the IL-4/Stat6 pathway in macrophages and the TGF-β/Smad3 pathway in fibroblasts, supporting a synergistic macrophage-fibroblast crosstalk loop that drives pulmonary fibrosis. siRNA-mediated silencing of Bcar3 protects mice from fibrosis in two models. siRNA knockdown, Stat6/Smad3 pathway analysis (Western blot), in vivo fibrosis models (bleomycin, FITC), human precision-cut lung slices, flow cytometry International journal of nanomedicine Medium 38414524
2025 BCAR3 promotes intrinsic cisplatin resistance in head and neck squamous cell carcinoma by sustaining TGF-β/SMAD signaling: BCAR3 increases phosphorylation of SMAD2 and facilitates transcriptional activation of SMAD4, suppressing mitochondria-derived apoptosis. Inhibition of TGF-β/SMAD signaling with galunisertib synergizes with cisplatin. Transcriptome analysis, Western blotting (pSMAD2, SMAD4), flow cytometry (apoptosis), BCAR3 knockdown in vitro and in vivo, pharmacological TGFβRI inhibition (galunisertib) Cellular signalling Medium 40935299
2016 A spontaneous 1-bp insertion in exon 7 of Bcar3 (producing a premature stop codon and truncated protein) in CF#1/lr mice causes autosomal recessive lens extrusion cataracts, independently confirming that BCAR3 loss disrupts lens integrity in vivo (consistent with the AND-34 knockout model). Whole-genome mapping, Sanger sequencing, histopathology, genetic complementation analysis Mammalian genome Medium 27364350
2006 CrkII associates with BCAR3 in human glomerular mesangial cells; ET-1 treatment time-dependently increases CrkII-BCAR3 complex formation, and this association is Pyk2-dependent (dominant-interfering Pyk2 reduces CrkII-BCAR3 association), placing BCAR3 downstream of Pyk2 and upstream of CrkII in ET-1 signaling. Co-immunoprecipitation, adenovirus-mediated dominant-interfering Pyk2 expression, ET-1 stimulation time-course Experimental biology and medicine Low 16740993
2021 BCAR3 participates in a pathway with the MET receptor to control proliferation and migration of triple-negative breast cancer cells; BCAR3 knockdown reduces tumor growth in orthotopic mouse models. In some TNBC backgrounds, BCAR3 activates an autocrine HGF loop to sustain MET signaling. siRNA/shRNA knockdown, orthotopic mouse tumor models, RNA expression database correlation, HGF/MET signaling assays, proliferation and migration assays American journal of cancer research Medium 34765292
2026 BCAR3 knockdown in thyroid cancer cells reduces AKT/mTOR phosphorylation and shifts EMT markers (increases E-cadherin, decreases vimentin and N-cadherin), suppressing proliferation, migration, and invasion; partial rescue with a PI3K activator supports BCAR3 acting upstream of PI3K/AKT/mTOR to promote EMT and invasive behavior. shRNA knockdown, Western blot (AKT/mTOR phosphorylation, EMT markers), proliferation/migration/invasion assays, PI3K activator rescue experiment Cancers Medium 41595187

Source papers

Stage 0 corpus · 79 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 Biochemical analysis, cpn60 and 16S rDNA sequence data indicate that Streptococcus suis serotypes 32 and 34, isolated from pigs, are Streptococcus orisratti. Veterinary microbiology 165 15795078
1986 Induction of 32- and 34-kDa stress proteins by sodium arsenite, heavy metals, and thiol-reactive agents. The Journal of biological chemistry 109 3093479
2011 Prevalence of DSM-IV borderline personality disorder in two community samples: 6,330 English 11-year-olds and 34,653 American adults. Journal of personality disorders 103 22023298
1998 Identification of BCAR3 by a random search for genes involved in antiestrogen resistance of human breast cancer cells. The EMBO journal 102 9582273
2000 p130Cas regulates the activity of AND-34, a novel Ral, Rap1, and R-Ras guanine nucleotide exchange factor. The Journal of biological chemistry 86 10896938
2017 A tRNA fragment, tRF5-Glu, regulates BCAR3 expression and proliferation in ovarian cancer cells. Oncotarget 85 29221134
2003 AND-34/BCAR3, a GDP exchange factor whose overexpression confers antiestrogen resistance, activates Rac, PAK1, and the cyclin D1 promoter. Cancer research 68 14583477
2003 Synergistic promotion of c-Src activation and cell migration by Cas and AND-34/BCAR3. The Journal of biological chemistry 65 12740391
2006 Roles of lipid peroxidation and cytoplasmic droplets on in vitro fertilization capacity of sperm collected from bovine epididymides stored at 4 and 34 degrees C. Theriogenology 59 17045637
2019 MicroRNA-126-5p downregulates BCAR3 expression to promote cell migration and invasion in endometriosis. Molecular and cellular endocrinology 49 31233772
2012 MIG-7 controls COX-2/PGE2-mediated lung cancer metastasis. Cancer research 45 23149922
1999 AND-34, a novel p130Cas-binding thymic stromal cell protein regulated by adhesion and inflammatory cytokines. Journal of immunology (Baltimore, Md. : 1950) 45 10438950
2005 AND-34 activates phosphatidylinositol 3-kinase and induces anti-estrogen resistance in a SH2 and GDP exchange factor-like domain-dependent manner. Molecular cancer research : MCR 41 15671247
2003 The GDP exchange factor AND-34 is expressed in B cells, associates with HEF1, and activates Cdc42. Journal of immunology (Baltimore, Md. : 1950) 38 12517963
2013 Breast cancer antiestrogen resistance 3 (BCAR3) promotes cell motility by regulating actin cytoskeletal and adhesion remodeling in invasive breast cancer cells. PloS one 35 23762409
2014 Expanded spectrum of exon 33 and 34 mutations in SRCAP and follow-up in patients with Floating-Harbor syndrome. BMC medical genetics 34 25433523
2012 Protein tyrosine phosphatase α phosphotyrosyl-789 binds BCAR3 to position Cas for activation at integrin-mediated focal adhesions. Molecular and cellular biology 34 22801373
1988 Colocalization of F-actin and 34-kilodalton actin bundling protein in Dictyostelium amoebae and cultured fibroblasts. Cell motility and the cytoskeleton 32 3284657
2007 Eimeria macusaniensis infection in 15 llamas and 34 alpacas. Journal of the American Veterinary Medical Association 31 17199499
2007 AND-34/BCAR3 differs from other NSP homologs in induction of anti-estrogen resistance, cyclin D1 promoter activation and altered breast cancer cell morphology. Journal of cellular physiology 31 17427198
2007 Overexpression of carcinoma and embryonic cytotrophoblast cell-specific Mig-7 induces invasion and vessel-like structure formation. The American journal of pathology 31 17456780
1984 Bacteriophage SPO1 genes 33 and 34. Location and primary structure of genes encoding regulatory subunits of Bacillus subtilis RNA polymerase. Journal of molecular biology 29 6441846
2016 PEDF and 34-mer inhibit angiogenesis in the heart by inducing tip cells apoptosis via up-regulating PPAR-γ to increase surface FasL. Apoptosis : an international journal on programmed cell death 28 26519036
2014 Association of the breast cancer antiestrogen resistance protein 1 (BCAR1) and BCAR3 scaffolding proteins in cell signaling and antiestrogen resistance. The Journal of biological chemistry 27 24584939
2009 Pyk2 mediates endothelin-1 signaling via p130Cas/BCAR3 cascade and regulates human glomerular mesangial cell adhesion and spreading. Journal of cellular physiology 26 19086031
2009 BCAR3 regulates Src/p130 Cas association, Src kinase activity, and breast cancer adhesion signaling. The Journal of biological chemistry 26 19940159
2004 Breast cancer oestrogen independence mediated by BCAR1 or BCAR3 genes is transmitted through mechanisms distinct from the oestrogen receptor signalling pathway or the epidermal growth factor receptor signalling pathway. Breast cancer research : BCR 26 15642172
2013 High-precision measurements of (33)S and (34)S fractionation during SO2 oxidation reveal causes of seasonality in SO2 and sulfate isotopic composition. Environmental science & technology 24 24079753
2008 Structural insights into the association between BCAR3 and Cas family members, an atypical complex implicated in anti-oestrogen resistance. Journal of molecular biology 24 19103205
2015 MIG-7 and phosphorylated prohibitin coordinately regulate lung cancer invasion/metastasis. Oncotarget 23 25575814
2014 Recombinant viral capsid protein VP1 suppresses lung cancer metastasis by inhibiting COX-2/PGE2 and MIG-7. Oncotarget 20 25004182
2009 AND-34/BCAR3 regulates adhesion-dependent p130Cas serine phosphorylation and breast cancer cell growth pattern. Cellular signalling 20 19454314
2002 Salmonella enterica serotype Enteritidis phage types 4, 7, 6, 8, 13a, 29 and 34: a comparative analysis of genomic fingerprints from geographically distant isolates. Journal of applied microbiology 20 11849346
2011 BCAR3/AND-34 can signal independent of complex formation with CAS family members or the presence of p130Cas. Cellular signalling 19 21262352
2017 Molecular characterization and expression analysis of large yellow croaker (Larimichthys crocea) interleukin-12A, 16 and 34 after poly I:C and Vibrio anguillarum challenge. Fish & shellfish immunology 18 29292198
2012 Breast cancer anti-estrogen resistance 3 (BCAR3) protein augments binding of the c-Src SH3 domain to Crk-associated substrate (p130cas). The Journal of biological chemistry 18 22711540
2007 Splice variants and expression patterns of SHEP1, BCAR3 and NSP1, a gene family involved in integrin and receptor tyrosine kinase signaling. Gene 18 17270363
2009 Loss of AND-34/BCAR3 expression in mice results in rupture of the adult lens. Molecular vision 17 19365570
2008 BCAR3 regulates EGF-induced DNA synthesis in normal human breast MCF-12A cells. Biochemical and biophysical research communications 16 18722344
2005 Carcinoma cell-specific Mig-7: a new potential marker for circulating and migrating cancer cells. Oncology reports 16 15583799
2017 The Role of Cysteine String Protein α Phosphorylation at Serine 10 and 34 by Protein Kinase Cγ for Presynaptic Maintenance. The Journal of neuroscience : the official journal of the Society for Neuroscience 13 29167402
2017 MIG7 is involved in vasculogenic mimicry formation rendering invasion and metastasis in hepatocellular carcinoma. Oncology reports 13 29251318
1996 Identification of the antigenic determinants of factors 8, 9, and 34 of genus Candida. FEBS letters 13 8898075
2024 Localized Administration of Bcar3 siRNA via Nano-Self-Assembly to Treat Idiopathic Pulmonary Fibrosis by Disrupting Macrophage-Fibroblast Crosstalk. International journal of nanomedicine 11 38414524
2024 PEDF and 34-mer peptide inhibit cardiac microvascular endothelial cell ferroptosis via Nrf2/HO-1 signalling in myocardial ischemia-reperfusion injury. Journal of cellular and molecular medicine 10 39048917
2021 Breast Cancer Antiestrogen Resistance 3 (BCAR3) promotes tumor growth and progression in triple-negative breast cancer. American journal of cancer research 10 34765292
2020 Involvement of interleukins-17 and -34 in exacerbated orthodontic root resorption by jiggling force during rat experimental tooth movement. Journal of the World federation of orthodontists 9 32672655
2014 Reference intervals for N-terminal pro-B-type natriuretic peptide in amniotic fluid between 10 and 34 weeks of gestation. PloS one 9 25490554
2017 A reverse-hybridization test for the identification of 76 pneumococcal serotypes, 42 individually and 34 in pairs. Journal of microbiological methods 8 28818600
2021 A Cas-BCAR3 co-regulatory circuit controls lamellipodia dynamics. eLife 7 34169835
2013 Functional roles of BCAR3 in the signaling pathways of insulin leading to DNA synthesis, membrane ruffling and GLUT4 translocation. Biochemical and biophysical research communications 7 24216110
2006 CrkII associates with BCAR3 in response to endothelin-1 in human glomerular mesangial cells. Experimental biology and medicine (Maywood, N.J.) 7 16740993
2006 Characterization of AND-34 function and signaling. Methods in enzymology 7 16757314
1987 Cardiac abnormalities in myotonic dystrophy. Electrocardiographic and echocardiographic findings in 65 patients and 34 of their unaffected relatives. Relation with age and sex and relevance for gene detection. Journal of the neurological sciences 7 3681332
2019 Silencing of Mig-7 expression inhibits in-vitro invasiveness and vasculogenic mimicry of human glioma U87 Cells. Neuroreport 6 31688418
2005 Endostatin phenylalanines 31 and 34 define a receptor binding site. Genes to cells : devoted to molecular & cellular mechanisms 6 16115201
2022 MiR-199a/b-3p inhibits colorectal cancer cell proliferation, migration and invasion through targeting PAK4 and BCAR3. European journal of medical research 5 35842733
2017 Mig-7 expression and vasculogenic mimicry in malignant ovarian tumors. Ginekologia polska 5 29192416
2015 Expression pattern of bcar3, a downstream target of Gata2, and its binding partner, bcar1, during Xenopus development. Gene expression patterns : GEP 5 26631802
2021 Craniofacial and Craniocervical Features in Cartilage-Hair Hypoplasia: A Radiological Study of 17 Patients and 34 Controls. Frontiers in endocrinology 4 34956076
2013 [Expressions and clinical significance of vasculogenic mimicry and related protein Mig-7 and MMP-2 in gastric carcinoma]. Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology 4 23388341
2024 Deciphering the Role of BCAR3 in Cancer Progression: Gene Regulation, Signal Transduction, and Therapeutic Implications. Cancers 3 38730626
2022 Comprehensive immunohistochemical analysis of RET, BCAR1, and BCAR3 expression in patients with Luminal A and B breast cancer subtypes. Breast cancer research and treatment 3 35031902
2016 A novel spontaneous mutation of BCAR3 results in extrusion cataracts in CF#1 mouse strain. Mammalian genome : official journal of the International Mammalian Genome Society 3 27364350
1995 Enhanced phosphorylation of nuclear 21-kDa and 34-kDa proteins in hepatoma cell death induced by tumor-necrosis factor-alpha. European journal of biochemistry 3 7556142
1977 Replicon number and growth rate in fathead minnow cells cultured at 14 and 34 degrees C. Cell and tissue kinetics 3 922802
2019 [Mig-7 gene silencing inhibits vasculogenic mimicry formation and invasion of glioma U251 cells in vitro by suppressing MEK/ERK signaling]. Nan fang yi ke da xue xue bao = Journal of Southern Medical University 2 31140421
2016 Production, characterization, and in vitro effects of a novel monoclonal antibody against Mig-7. Biochemical and biophysical research communications 2 27181359
2011 Bcar3 is expressed in sertoli cells and germ cells of the developing testis in mice. Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation 2 21654156
2022 Association between Genetic Polymorphisms in MicroRNAs 196a2 (rs11614913) and 34 b/c (rs4938723) and Risk of Hepatocellular Carcinoma in Egyptian Patients. Asian Pacific journal of cancer prevention : APJCP 1 35485699
2016 [Inhibitory effect of Mig-7 silencing by retrovirus-mediated shRNA on vasculogenic mimicry, invasion and metastasis of human hepatocellular carcinoma cells in vitro]. Nan fang yi ke da xue xue bao = Journal of Southern Medical University 1 27881337
2012 [Mig-7 enhances vasculogenic mimicry in gastric cancer cells]. Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology 1 23127401
2026 BCAR3 Hypomethylation as a Potential Diagnostic Marker for Thyroid Cancer and Its Mechanism via Promoting EMT and AKT/mTOR Pathway. Cancers 0 41595187
2026 Trefoil factor family 3 (TFF3) and migration inducting gene 7 (MIG7) as molecular markers for early detection of endometrial carcinoma micro metastases. BMC cancer 0 41888758
2026 RETRACTION: PEDF and 34-mer Peptide Inhibit Cardiac Microvascular Endothelial Cell Ferroptosis via Nrf2/HO-1 Signalling in Myocardial Ischemia-Reperfusion Injury. Journal of cellular and molecular medicine 0 42169367
2025 BCAR3 confers resistance to cisplatin in head and neck squamous cell carcinoma by sustaining TGF-β/SMAD signaling. Cellular signalling 0 40935299
2025 A cellular epithelioid hemangioma of the liver harboring a novel FOS::BCAR3 fusion gene. Virchows Archiv : an international journal of pathology 0 41251743
2017 [MIG7 Regulates the Vasculogenic Mimicry Formation in Hepatocellular Carcinoma then Effects the Metastasis Potential of HCC]. Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition 0 28616909
1981 Reproduction of attenuated mumps virus in dog kidney cell cultures precultivated at 37 and 34 degrees C. Acta virologica 0 6118051

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