Affinage

BCAR1

Breast cancer anti-estrogen resistance protein 1 · UniProt P56945

Length
870 aa
Mass
93.4 kDa
Annotated
2026-04-28
100 papers in source corpus 21 papers cited in narrative 21 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

BCAR1 (p130Cas) is a multi-domain scaffold protein that integrates integrin, receptor tyrosine kinase, and mechanical force signals at focal adhesions to coordinate actin cytoskeletal organization, cell migration, survival, and gene expression. It localizes to focal adhesions via its N-terminal SH3 domain (binding FAK) and C-terminal CCH domain, and to filopodia tips where it senses ECM stiffness; its substrate domain, containing multiple tyrosine residues phosphorylated by Src, FAK, Ack1, and NPM-ALK, assembles signaling complexes with Crk, PI3K-p85, Grb2, PYK2, estrogen receptor-α/Src, and PKN3 to activate Rac1, ERK1/2, and PI3K cascades driving cell spreading, migration, anti-estrogen resistance in breast cancer, and ALK-mediated oncogenic transformation (PMID:9697697, PMID:10799562, PMID:17038317, PMID:16105984, PMID:15020686, PMID:20430882, PMID:19412734). BCAR1 also translocates to the nucleus under mechanical shear stress to suppress NF-κB–dependent RANKL expression in osteocytes, and conditional knockout causes osteopenia, while germline deletion is embryonic lethal due to cardiovascular defects (PMID:31579816, PMID:9697697). Through SRC-dependent signaling via DOCK1–RAC1–β-catenin, BCAR1 sustains MYC transcription in KRAS-mutant pancreatic cancer and promotes E-cadherin lysosomal degradation, linking it to epithelial–mesenchymal plasticity and synthetic lethal vulnerability with ERK pathway inhibition (PMID:34192548, PMID:21765937).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 1998 High

    Establishing that p130Cas is essential in vivo — germline knockout revealed embryonic lethality from cardiovascular defects and showed Cas-null fibroblasts fail to assemble actin stress fibers or support Src-induced podosome formation, defining BCAR1 as a non-redundant integrator of cytoskeletal and oncogenic signaling.

    Evidence Cas-deficient knockout mice and primary MEF phenotypic/rescue analysis

    PMID:9697697

    Open questions at the time
    • Molecular basis of cardiovascular lethality not defined
    • Which substrate-domain phosphosites are rate-limiting for stress fiber rescue unclear
  2. 1998 Medium

    Identifying PKC-epsilon as an alternative pathway regulating p130Cas phosphorylation in neurons extended the kinase repertoire beyond Src-family kinases and placed BCAR1 in growth cone dynamics.

    Evidence PKC/Src inhibitor pharmacology, growth cone fractionation, and PKC-epsilon transfection in neuroblastoma cells

    PMID:9442079

    Open questions at the time
    • Whether PKC-epsilon phosphorylates Cas directly or acts through an intermediary kinase not resolved
    • Functional consequence of PKC-mediated Cas phosphorylation on axon outgrowth not tested
  3. 1999 High

    Demonstrating that Cdc42/Ack1 phosphorylates p130Cas and that PYK2 binds Cas via the SH3 domain expanded the upstream kinase network and linked BCAR1 to integrin-β3 signaling in osteoclasts and MCSP signaling in melanoma.

    Evidence Co-IP with domain mapping, dominant-negative Cdc42/Ack1, integrin ligation assays in osteoclasts and melanoma cells

    PMID:10587647 PMID:9988732

    Open questions at the time
    • Whether Ack1 and PYK2 phosphorylate overlapping or distinct substrate-domain sites not resolved
  4. 2000 High

    Mapping the p130Cas proline-rich domain interaction with PI3K-p85 SH3 established a direct biochemical link to PI3K activation and showed functional importance for integrin-mediated adenovirus internalization.

    Evidence Dominant-negative constructs, peptide-SH3 binding assay, co-IP in adenovirus entry system

    PMID:10799562

    Open questions at the time
    • Whether Cas–PI3K interaction contributes to canonical integrin survival signaling beyond viral entry not tested
  5. 2001 Medium

    Identification of PP2A as a serine phosphatase for p130Cas and placement of Cas in a nephrocystin–PYK2 focal adhesion complex expanded the regulatory circuitry to include cell-cycle-dependent dephosphorylation and renal epithelial signaling.

    Evidence Co-IP, in vitro phosphatase assay, okadaic acid treatment; nephrocystin co-IP with downstream ERK readout

    PMID:11493697 PMID:11593413

    Open questions at the time
    • Specific PP2A holoenzyme complex identity not determined
    • Nephrocystin–Cas interaction awaits reciprocal validation
  6. 2002 High

    Showing that Cas-null MEFs phenocopy FAK-null MEFs in failing to spread on ephrinA1 substrates established BCAR1 as a co-obligate effector of Eph receptor signaling alongside FAK.

    Evidence FAK−/− and Cas−/− MEFs, re-expression rescue, phosphotyrosine blotting

    PMID:12134157

    Open questions at the time
    • Whether FAK directly phosphorylates Cas in the Eph signaling context not biochemically demonstrated
  7. 2004 High

    Discovering that estrogen receptor-α recruits p130Cas into a ternary complex with c-Src to activate ERK and cyclin D1 connected BCAR1 to non-genomic estrogen signaling and anti-estrogen resistance in breast cancer.

    Evidence Co-IP, siRNA, Src kinase assay, cyclin D1 readout in T47D cells

    PMID:15020686

    Open questions at the time
    • Whether the ERα–Cas complex forms in vivo in breast tumors not shown
  8. 2004 Medium

    Demonstrating caspase/calpain cleavage of Cas during anoikis, with the cleavage product itself inducing apoptosis, revealed a dual pro-survival/pro-death switch function for BCAR1.

    Evidence Anoikis assay with protease inhibitors, overexpression of cleavage product, apoptosis readout

    PMID:14743392

    Open questions at the time
    • Identity of non-caspase/non-calpain protease not determined
    • Physiological relevance of cleavage product-induced apoptosis in vivo not tested
  9. 2005 High

    Establishing that p130Cas is indispensable for NPM-ALK oncogenic transformation — Cas-null fibroblasts expressing NPM-ALK fail to depolymerize actin or transform — defined BCAR1 as a critical ALK effector via Grb2-dependent recruitment.

    Evidence Mass spectrometry interactomics, kinase-dead ALK, dominant-negative Grb2, Cas−/− fibroblast transformation assay

    PMID:16105984

    Open questions at the time
    • Whether Cas is required for ALK-driven transformation in lymphoma cells in vivo not tested
  10. 2006 High

    Direct kinase assay showing Ack1 phosphorylates the Cas substrate domain, with SH3–SH3 mediated Ack1–Cas binding and siRNA confirming both are required for Cdc42-driven migration, resolved the kinase identity downstream of Cdc42.

    Evidence Domain mapping, in vitro kinase assay, siRNA of Ack1 and Cas, collagen migration

    PMID:17038317

    Open questions at the time
    • Specific Ack1-phosphorylated tyrosine residues on Cas not mapped
  11. 2009 Medium

    Systematic domain-swap between BCAR1 and HEF1/NEDD9 pinpointed the substrate domain as uniquely sufficient to confer anti-estrogen resistant proliferation, narrowing the functional determinant to its tyrosine phosphorylation sites.

    Evidence Chimeric BCAR1/HEF1 constructs, anti-estrogen resistance proliferation assay in breast cancer cells

    PMID:19412734

    Open questions at the time
    • Which individual substrate-domain phosphosites are necessary for anti-estrogen resistance not identified
  12. 2010 High

    Live-cell imaging and FRAP revealed two redundant FA-targeting mechanisms — the SH3 domain (via FAK) and the CCH domain — explaining how BCAR1 maintains focal adhesion residence throughout the adhesion lifecycle.

    Evidence Domain-deletion mutants, FRAP, live fluorescence microscopy, migration assay

    PMID:20430882

    Open questions at the time
    • Binding partner of CCH domain at FAs not identified
  13. 2011 Medium

    Showing that BCAR1 promotes SRC-dependent E-cadherin lysosomal degradation without affecting transcription linked Cas to post-translational regulation of epithelial cell–cell adhesion.

    Evidence siRNA/shRNA, Src inhibitor, lysosomal inhibition, E-cadherin localization, MMTV-PyT mouse model

    PMID:21765937

    Open questions at the time
    • E3 ubiquitin ligase downstream of Cas–Src that targets E-cadherin not identified
    • Whether BCAR1 and NEDD9 act redundantly or additively not fully resolved
  14. 2018 High

    Identification of PKN3 as the first Ser/Thr kinase to directly phosphorylate p130Cas via SH3–polyproline interaction expanded the signaling code beyond tyrosine phosphorylation and showed Src-independent roles for Cas in cell growth and invasion.

    Evidence In vitro kinase assay, domain-level co-IP, Cas−/− MEF rescue, co-localization

    PMID:30422386

    Open questions at the time
    • Specific Ser/Thr residues phosphorylated by PKN3 on Cas not mapped
    • Downstream effectors of PKN3-phosphorylated Cas not characterized
  15. 2019 High

    Discovery that BCAR1 localizes to filopodia tips via its CCH domain and controls filopodia stability in response to ECM stiffness established it as a bona fide mechanosensor at cellular protrusions, complementing its known role at focal adhesions.

    Evidence SIM screen of 80 adhesion proteins, domain-deletion constructs, siRNA, live imaging, filopodia stability assay

    PMID:30639111

    Open questions at the time
    • Molecular mechanism by which CCH domain senses stiffness at filopodia not resolved
  16. 2019 High

    Conditional knockout in osteocytes revealed that shear-stress-induced nuclear translocation of p130Cas suppresses NF-κB to limit RANKL expression and osteoclastogenesis, establishing a mechanotransduction–transcription axis for bone homeostasis.

    Evidence Osteocyte-specific Cas conditional KO mouse, shear stress in vitro, NF-κB reporter, bone histomorphometry

    PMID:31579816

    Open questions at the time
    • Mechanism of Cas nuclear import under shear stress not identified
    • Whether nuclear Cas directly binds NF-κB subunits or acts indirectly not determined
  17. 2021 High

    Genome-scale CRISPR screens identified BCAR1 as a top synthetic lethal partner with mutant KRAS; mechanistic dissection showed Src-dependent Cas phosphorylation sustains MYC transcription via DOCK1–RAC1–β-catenin, creating a druggable vulnerability when combined with ERK inhibition.

    Evidence CRISPR-Cas9 screen, siRNA screen, Src inhibitor, DOCK1/RAC1/β-catenin pathway analysis in pancreatic cancer cells

    PMID:34192548

    Open questions at the time
    • Whether Cas directly binds DOCK1 or acts through Crk adaptor not resolved
    • In vivo validation of Src + ERK inhibitor combination via Cas suppression not shown
  18. 2023 Medium

    FLOT1-mediated phosphorylation and nuclear translocation of BCAR1 at Y410 drives gastric cancer migration via ERK, extending the Cas nuclear signaling paradigm to an additional cancer context.

    Evidence Co-IP, Y410F phosphomutant rescue, siRNA, ERK inhibitor in gastric cancer cells

    PMID:37928269

    Open questions at the time
    • Whether FLOT1 directly phosphorylates Cas or recruits an intermediary kinase not determined
    • Nuclear function of Cas in gastric cancer cells not mechanistically defined beyond ERK dependence

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of substrate-domain mechanosensing, identity of the nuclear import machinery for Cas, the precise Ser/Thr phosphorylation sites targeted by PKN3, and whether nuclear Cas directly contacts NF-κB or chromatin.
  • No structural model of the full-length Cas scaffold exists
  • Nuclear import mechanism unknown
  • Full phosphosite map linking individual kinases to specific residues incomplete

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 6 GO:0008092 cytoskeletal protein binding 3
Localization
GO:0005856 cytoskeleton 4 GO:0005634 nucleus 2 GO:0005886 plasma membrane 2
Pathway
R-HSA-162582 Signal Transduction 6 R-HSA-1474244 Extracellular matrix organization 3 R-HSA-1643685 Disease 3 R-HSA-1266738 Developmental Biology 2 R-HSA-1500931 Cell-Cell communication 1 R-HSA-5357801 Programmed Cell Death 1
Partners
CRKGRB2PIK3R1PKN3PTK2PYK2SRCTNK2
Complex memberships
Cdc42–Ack1–Cas–Crk complexERα–Src–Cas–PI3K complexFAK–Cas focal adhesion complex

Evidence

Reading pass · 21 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 p130Cas (BCAR1) is required for actin stress fiber formation and Src-induced transformation; p130Cas-deficient embryos die in utero with cardiovascular defects, and Cas-null fibroblasts show severely impaired actin filament assembly and fail to form fully transformed podosomes in response to activated Src. Germline knockout mouse (Cas/Crkas-deficient), primary fibroblast phenotypic analysis, electron microscopy of myofibrils, and re-expression rescue Nature genetics High 9697697
1999 MCSP (melanoma chondroitin sulphate proteoglycan) stimulation recruits tyrosine-phosphorylated p130Cas through a pathway requiring Cdc42 activation and the Cdc42-associated kinase Ack-1; Ack-1 or Cdc42 inhibition abrogates MCSP-induced p130Cas phosphorylation and melanoma cell spreading. Co-immunoprecipitation, dominant-negative and inhibitory constructs for Cdc42 and Ack-1, tyrosine phosphorylation assays, cell spreading assays Nature cell biology High 10587647
1999 p130Cas forms a stable complex with PYK2 in osteoclasts, mediated by the SH3 domain of p130Cas and the C-terminal domain of PYK2; both co-localize in the sealing zone and podosomal structures, and p130Cas is tyrosine-phosphorylated upon integrin/β3-integrin ligation. Co-immunoprecipitation, domain-deletion mapping, immunofluorescence co-localization, tyrosine phosphorylation assays in osteoclast-like cells The Journal of biological chemistry High 9988732
2000 p130Cas associates with the p85 subunit of PI 3-kinase through its proline-rich domain (specifically the RPLPSPP motif interacting with the SH3 domain of p85), and this interaction is required for adenovirus internalization mediated by αv integrins; deletion of the substrate domain or proline-rich domain of p130Cas blocks Ad cell entry. Dominant-negative p130Cas constructs, co-immunoprecipitation, tyrphostin/genistein inhibition of p130Cas phosphorylation, peptide-SH3 domain binding assay The Journal of biological chemistry High 10799562
2001 Nephrocystin (NPHP1) physically interacts with p130Cas, PYK2, and tensin as detected by immunoprecipitation; nephrocystin expression triggers phosphorylation of PYK2 at Y402 and downstream ERK1/2 activation, placing p130Cas in the nephrocystin-PYK2 focal adhesion signaling complex. Immunoprecipitation of endogenous proteins, Western blot for PYK2-Y402 phosphorylation and MAPK activation Proceedings of the National Academy of Sciences of the United States of America Medium 11493697
2001 PP2A (protein phosphatase 2A) associates with p130Cas and dephosphorylates serine residues on Cas in vitro; okadaic acid (PP2A inhibitor) augments mitotic serine/threonine phosphorylation of Cas, placing PP2A as an eraser of cell-cycle-regulated serine phosphorylation on p130Cas. Co-immunoprecipitation, microcystin pulldown, in vitro phosphatase assay, okadaic acid treatment Oncogene Medium 11593413
2002 EphrinA1-induced cell spreading and actin cytoskeletal reorganization require both FAK and p130Cas; MEFs from FAK-/- or p130Cas-/- mice show severe defects in ephrinA1-induced spreading that are rescued by re-expression of the respective proteins; EphA2, FAK, and p130Cas are the major ephrin-dependent phosphotyrosyl proteins during this response. MEFs from FAK-/- and p130Cas-/- knockout mice, re-expression rescue, phosphotyrosine Western blot, cell morphology assays on ephrinA1-coated surfaces Nature cell biology High 12134157
2004 p130Cas rapidly associates (within 3 minutes) with estrogen receptor alpha in a multi-molecular complex containing c-Src and p85/PI3K upon estrogen treatment in T47D breast cancer cells; this association is c-Src-dependent; p130Cas overexpression enhances estrogen-dependent Src kinase and ERK1/2 activation, while siRNA silencing of p130Cas inhibits estrogen-dependent ERK1/2 activity and cyclin D1 induction. Co-immunoprecipitation, siRNA knockdown, kinase activity assays, cyclin D1 expression analysis Journal of cell science High 15020686
2004 p130Cas is specifically cleaved during anoikis by caspases, calpain, and additional unidentified proteases; overexpression of the p130Cas cleavage product induces apoptosis, suggesting p130Cas has a dual role—mediating survival when cells are attached and participating in cell death execution upon loss of matrix contact. Anoikis assay, caspase/calpain inhibitors, overexpression of cleavage product, apoptosis readout Journal of cellular biochemistry Medium 14743392
2005 NPM-ALK binds p130Cas and induces its tyrosine phosphorylation in a Grb2-dependent and ALK-kinase-activity-dependent manner; p130Cas-/- fibroblasts expressing NPM-ALK fail to depolymerize actin filaments and are no longer transformed, establishing p130Cas as essential for ALK-mediated oncogenic transformation. Mass spectrometry-based interactomics, co-immunoprecipitation, kinase-dead mutant, dominant-negative Grb2, p130Cas-/- fibroblasts, transformation assay Blood High 16105984
2006 Ack1 directly phosphorylates the substrate domain of p130Cas and forms a signaling complex with Cdc42, p130Cas, and Crk; the Ack1-p130Cas interaction is mediated by their respective SH3 domains; siRNA knockdown of either Ack1 or p130Cas blocks Cdc42-induced cell migration on collagen. Co-immunoprecipitation, siRNA knockdown, collagen-based migration assay, domain interaction mapping, phosphorylation assay The Journal of biological chemistry High 17038317
2007 Drosophila Cas (DCas), the ortholog of p130Cas, functions in neurons to regulate axon guidance by controlling the degree of axon fasciculation; genetic epistasis shows integrins function together with Cas in this process. Drosophila genetics, loss-of-function mutants, genetic epistasis with integrin mutants, axon guidance phenotyping Development (Cambridge, England) Medium 17537798
2009 The substrate domain of BCAR1 (containing multiple tyrosine phosphorylation sites) is essential for anti-estrogen-resistant proliferation of breast cancer cells, as determined by chimeric BCAR1/HEF1 domain-swap analysis; SH3 and C-terminal domains are not sufficient and the central substrate domain uniquely confers resistance. Domain-swap chimeric protein expression, anti-estrogen resistance proliferation assay in human breast cancer cells Breast cancer research and treatment Medium 19412734
2010 p130Cas localizes to focal adhesions throughout their assembly and disassembly via two redundant targeting mechanisms: the N-terminal SH3 domain (which recruits FAK) and the C-terminal Cas-family homology (CCH) domain; deletion of either domain significantly impairs FA localization and tyrosine phosphorylation, and deletion of both fully excludes p130Cas from FAs. Live cell fluorescence microscopy, domain-deletion mutants, FRAP, FAK interaction assay, cell migration assay The Journal of biological chemistry High 20430882
2011 BCAR1 (and NEDD9) negatively regulate E-cadherin membrane localization and promote E-cadherin lysosomal degradation by signaling through SRC; Cas proteins do not affect E-cadherin transcription but stimulate its removal from the cell membrane. siRNA/shRNA knockdown, lysosomal inhibition assay, Src inhibitor treatment, E-cadherin localization by immunofluorescence, MMTV-PyT mouse model with Nedd9 knockout PloS one Medium 21765937
2018 p130Cas directly interacts with the Ser/Thr kinase PKN3 via the p130Cas SH3 domain and a centrally located PKN3 polyproline sequence; PKN3 is the first identified Ser/Thr kinase to bind and phosphorylate p130Cas, and this interaction is important for cell growth and invasiveness independent of Src transformation. Co-immunoprecipitation, domain-deletion mapping, in vitro kinase assay, co-localization by microscopy, p130Cas-/- MEF rescue Molecular oncology High 30422386
2019 p130Cas (BCAR1) is recruited to filopodia tips via its C-terminal Cas family homology domain (CCHD) and acts as a mechanosensitive regulator of filopodia stability; BCAR1 knockdown reduces filopodia stability in response to ECM stiffness cues. Structured-illumination microscopy screen of 80 adhesion proteins, live imaging, domain-deletion constructs, siRNA knockdown, filopodia stability assay Current biology : CB High 30639111
2019 p130Cas translocates to the nucleus under fluid shear stress in osteocytes and down-regulates NF-κB activity; Cas deficiency in osteocytes increases NF-κB-mediated RANKL expression and osteoclastic bone resorption, resulting in osteopenia; shear stress-dependent Cas-NF-κB interplay supports bone homeostasis. Osteocyte-specific Cas conditional knockout mouse, shear stress application on cultured osteocytes, NF-κB reporter assay, RANKL expression, bone histomorphometry Science advances High 31579816
2021 Suppression of BCAR1 sensitizes pancreatic cancer cells to ERK inhibition; SRC-inhibitor-mediated suppression of p130Cas phosphorylation impairs MYC transcription through a DOCK1-RAC1-β-catenin-dependent mechanism; BCAR1 is a top synthetic lethal interactor with mutant KRAS in genome-scale CRISPR screens. siRNA screen, genome-scale CRISPR-Cas9 screen, SRC inhibitor treatment, DOCK1/RAC1/β-catenin pathway analysis, MYC transcription and protein level assays, ERK inhibitor combination Cell reports High 34192548
2023 FLOT1 interacts with BCAR1 and promotes its phosphorylation and nuclear translocation; FLOT1-induced gastric cancer cell proliferation, migration, and invasion are blocked by BCAR1 knockdown; re-expression of wild-type but not Y410F mutant BCAR1 partially restores FLOT1-knockdown-induced migration defects, and this restoration is inhibited by ERK inhibitor. Co-immunoprecipitation, site-directed mutagenesis (Y410F), siRNA knockdown, overexpression, ERK inhibitor treatment, migration/invasion assays International journal of biological sciences Medium 37928269
1998 p130Cas tyrosine phosphorylation in differentiating neuroblastoma cells is regulated by PKC (specifically PKC-epsilon) and is resistant to Src-family kinase inhibitor herbimycin A at early time points; p130Cas and its phosphorylated form are present in growth cones, and PKC inhibition causes growth-cone filopodial retraction with concurrent loss of p130Cas phosphorylation. PKC inhibitor (GF 109203X), herbimycin A, transient transfection of active PKC-epsilon and v-Src, growth cone isolation, immunoblot for p130Cas phosphorylation The Journal of biological chemistry Medium 9442079

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2013 Multiplex genome engineering using CRISPR/Cas systems. Science (New York, N.Y.) 11293 23287718
2014 CRISPR-Cas systems for editing, regulating and targeting genomes. Nature biotechnology 2203 24584096
2019 The next generation of CRISPR-Cas technologies and applications. Nature reviews. Molecular cell biology 1002 31147612
2017 Diversity, classification and evolution of CRISPR-Cas systems. Current opinion in microbiology 967 28605718
2016 New CRISPR-Cas systems from uncultivated microbes. Nature 398 28005056
1998 Cardiovascular anomaly, impaired actin bundling and resistance to Src-induced transformation in mice lacking p130Cas. Nature genetics 309 9697697
2017 CRISPR-Cas: Adapting to change. Science (New York, N.Y.) 308 28385959
2019 Origins and evolution of CRISPR-Cas systems. Philosophical transactions of the Royal Society of London. Series B, Biological sciences 296 30905284
2016 CRISPR-Cas: biology, mechanisms and relevance. Philosophical transactions of the Royal Society of London. Series B, Biological sciences 275 27672148
2015 Annotation and Classification of CRISPR-Cas Systems. Methods in molecular biology (Clifton, N.J.) 272 25981466
2021 The CRISPR-Cas toolbox and gene editing technologies. Molecular cell 250 34968414
2015 Applications of CRISPR-Cas systems in neuroscience. Nature reviews. Neuroscience 211 26656253
2019 Molecular mechanisms of CRISPR-Cas spacer acquisition. Nature reviews. Microbiology 186 30171202
2016 Adaptation in CRISPR-Cas Systems. Molecular cell 178 26949040
1999 Melanoma chondroitin sulphate proteoglycan regulates cell spreading through Cdc42, Ack-1 and p130cas. Nature cell biology 172 10587647
2017 DNA epigenome editing using CRISPR-Cas SunTag-directed DNMT3A. Genome biology 171 28923089
2018 Classification and Nomenclature of CRISPR-Cas Systems: Where from Here? The CRISPR journal 165 31021272
2002 EphrinA1-induced cytoskeletal re-organization requires FAK and p130(cas). Nature cell biology 158 12134157
2016 Breaking-Cas-interactive design of guide RNAs for CRISPR-Cas experiments for ENSEMBL genomes. Nucleic acids research 148 27166368
2020 Molecular Mechanisms of CRISPR-Cas Immunity in Bacteria. Annual review of genetics 141 32857635
2017 Advances in Industrial Biotechnology Using CRISPR-Cas Systems. Trends in biotechnology 133 28778606
2015 The structural biology of CRISPR-Cas systems. Current opinion in structural biology 125 25723899
2020 CRISPR/Cas gene therapy. Journal of cellular physiology 117 32959897
2004 p130Cas interacts with estrogen receptor alpha and modulates non-genomic estrogen signaling in breast cancer cells. Journal of cell science 103 15020686
2003 CSE1L/CAS: its role in proliferation and apoptosis. Apoptosis : an international journal on programmed cell death 100 12510150
2019 CRISPR-Cas in Streptococcus pyogenes. RNA biology 97 30856357
2000 Association of p130CAS with phosphatidylinositol-3-OH kinase mediates adenovirus cell entry. The Journal of biological chemistry 94 10799562
2019 Advances in CRISPR-Cas systems for RNA targeting, tracking and editing. Biotechnology advances 92 30926472
1999 Stable association of PYK2 and p130(Cas) in osteoclasts and their co-localization in the sealing zone. The Journal of biological chemistry 92 9988732
2019 Dead Cas Systems: Types, Principles, and Applications. International journal of molecular sciences 90 31801211
2001 Nephrocystin interacts with Pyk2, p130(Cas), and tensin and triggers phosphorylation of Pyk2. Proceedings of the National Academy of Sciences of the United States of America 90 11493697
2019 Filopodome Mapping Identifies p130Cas as a Mechanosensitive Regulator of Filopodia Stability. Current biology : CB 89 30639111
2014 Mechanosensors in integrin signaling: the emerging role of p130Cas. European journal of cell biology 88 25062607
2017 Using CRISPR-Cas systems as antimicrobials. Current opinion in microbiology 83 28888103
2012 p130Cas: a key signalling node in health and disease. Cellular signalling 77 23277200
2022 RNA-targeting CRISPR-Cas systems. Nature reviews. Microbiology 73 36171275
2021 CRISPR/Cas-powered nanobiosensors for diagnostics. Biosensors & bioelectronics 71 34741959
2011 NEDD9 and BCAR1 negatively regulate E-cadherin membrane localization, and promote E-cadherin degradation. PloS one 67 21765937
2005 p130Cas mediates the transforming properties of the anaplastic lymphoma kinase. Blood 58 16105984
2021 Protoplasts: From Isolation to CRISPR/Cas Genome Editing Application. Frontiers in genome editing 57 34713263
2018 The applications of CRISPR/Cas system in molecular detection. Journal of cellular and molecular medicine 53 30338908
2006 Ack1 mediates Cdc42-dependent cell migration and signaling to p130Cas. The Journal of biological chemistry 53 17038317
2021 Interrogating lncRNA functions via CRISPR/Cas systems. RNA biology 51 33685382
2018 Functional Genomics via CRISPR-Cas. Journal of molecular biology 51 29959923
2022 A review on CRISPR/Cas-based epigenetic regulation in plants. International journal of biological macromolecules 50 36057300
2019 Drug Inducible CRISPR/Cas Systems. Computational and structural biotechnology journal 49 31462973
2021 Bacterial resistance to CRISPR-Cas antimicrobials. Scientific reports 48 34446818
2018 An Attenuated CRISPR-Cas System in Enterococcus faecalis Permits DNA Acquisition. mBio 46 29717009
2010 Dynamics and mechanism of p130Cas localization to focal adhesions. The Journal of biological chemistry 46 20430882
2023 A CRISPR-Cas Cure for HIV/AIDS. International journal of molecular sciences 44 36675077
2019 CRISPR-Cas bioinformatics. Methods (San Diego, Calif.) 44 31326596
2014 Exploiting CRISPR/Cas systems for biotechnology. BioEssays : news and reviews in molecular, cellular and developmental biology 44 24323919
2014 CAS proteins in health and disease: an update. IUBMB life 43 24962474
2018 The CRISPR-Cas system in Enterobacteriaceae. Pathogens and disease 42 29325038
2015 Boosting plant immunity with CRISPR/Cas. Genome biology 41 26585913
2000 BCAR1/p130Cas expression in untreated and acquired tamoxifen-resistant human breast carcinomas. International journal of cancer 40 11008210
2020 Bacterial alginate regulators and phage homologs repress CRISPR-Cas immunity. Nature microbiology 39 32203410
2020 Development and Application of CRISPR/Cas in Microbial Biotechnology. Frontiers in bioengineering and biotechnology 39 32695770
2015 p130Cas/BCAR1 scaffold protein in tissue homeostasis and pathogenesis. Gene 38 25727852
1998 Protein kinase C-dependent tyrosine phosphorylation of p130cas in differentiating neuroblastoma cells. The Journal of biological chemistry 35 9442079
2004 Cleavage of p130Cas in anoikis. Journal of cellular biochemistry 34 14743392
2020 Prophages are associated with extensive CRISPR-Cas auto-immunity. Nucleic acids research 33 33219687
2019 Mechanical regulation of bone homeostasis through p130Cas-mediated alleviation of NF-κB activity. Science advances 32 31579816
2007 BCAR1 expression in prostate cancer: association with 16q23 LOH status, tumor progression and EGFR/KAI1 staining. The Prostate 32 17192874
2015 Keeping CRISPR/Cas on-Target. Current issues in molecular biology 31 26453843
2021 Targeting p130Cas- and microtubule-dependent MYC regulation sensitizes pancreatic cancer to ERK MAPK inhibition. Cell reports 30 34192548
2020 Translating CRISPR-Cas Therapeutics: Approaches and Challenges. The CRISPR journal 30 32833535
2007 Crk-associated substrate (Cas) signaling protein functions with integrins to specify axon guidance during development. Development (Cambridge, England) 29 17537798
2023 Enhancing CRISPR/Cas systems with nanotechnology. Trends in biotechnology 25 37451945
2019 Characterization of Cas proteins for CRISPR-Cas editing in streptomycetes. Biotechnology and bioengineering 25 31090220
2009 p130 Crk-associated substrate (CAS) in vascular smooth muscle. Journal of cardiovascular pharmacology and therapeutics 25 19329671
2020 Current understanding of the cyanobacterial CRISPR-Cas systems and development of the synthetic CRISPR-Cas systems for cyanobacteria. Enzyme and microbial technology 24 32912679
2022 Protocellular CRISPR/Cas-Based Diffusive Communication Using Transcriptional RNA Signaling. Angewandte Chemie (International ed. in English) 23 35385207
2008 Hsp90{beta} and p130(cas): novel regulatory factors of MMP-13 expression in human osteoarthritic chondrocytes. Annals of the rheumatic diseases 23 18593760
2017 Dysregulation of Blimp1 transcriptional repressor unleashes p130Cas/ErbB2 breast cancer invasion. Scientific reports 22 28442738
2017 Gene Editing With TALEN and CRISPR/Cas in Rice. Progress in molecular biology and translational science 22 28712502
2019 Variability in the durability of CRISPR-Cas immunity. Philosophical transactions of the Royal Society of London. Series B, Biological sciences 21 30905283
2023 Insertion sequence transposition inactivates CRISPR-Cas immunity. Nature communications 20 37474569
2022 Biological function of calcium-sensing receptor (CAS) and its coupling calcium signaling in plants. Plant physiology and biochemistry : PPB 20 35398653
2019 Porphyromonas gingivalis and its CRISPR-Cas system. Journal of oral microbiology 20 31303969
2017 The Reverse Transcriptases Associated with CRISPR-Cas Systems. Scientific reports 20 28769116
2017 How bacteria control the CRISPR-Cas arsenal. Current opinion in microbiology 20 29169146
2013 Exploiting CRISPR/Cas: interference mechanisms and applications. International journal of molecular sciences 20 23857052
2020 BCAR1 promotes proliferation and cell growth in lung adenocarcinoma via upregulation of POLR2A. Thoracic cancer 19 33001583
2019 CRISPR-Cas, DNA Supercoiling, and Nucleoid-Associated Proteins. Trends in microbiology 19 31519332
2018 Shooting the messenger: RNA-targetting CRISPR-Cas systems. Bioscience reports 19 29748239
2001 Protein phosphatase 2A interacts with the Src kinase substrate p130(CAS). Oncogene 19 11593413
1996 Tyrosine phosphorylation of p130Cas in cell adhesion and transformation. Human cell 19 9183645
2018 High BCAR1 expression is associated with early PSA recurrence in ERG negative prostate cancer. BMC cancer 18 29304771
2015 Structure Principles of CRISPR-Cas Surveillance and Effector Complexes. Annual review of biophysics 18 26048003
2025 CRISPRoffT: comprehensive database of CRISPR/Cas off-targets. Nucleic acids research 17 39526384
2009 CAS: which stent for which lesion. The Journal of cardiovascular surgery 17 19935608
2024 An anti-CRISPR that pulls apart a CRISPR-Cas complex. Nature 16 38961300
2023 CRISPR/Cas-Based MicroRNA Biosensors. Chemistry (Weinheim an der Bergstrasse, Germany) 16 36477884
2021 The Challenge of CRISPR-Cas Toward Bioethics. Frontiers in microbiology 16 34122373
2009 The substrate domain of BCAR1 is essential for anti-estrogen-resistant proliferation of human breast cancer cells. Breast cancer research and treatment 16 19412734
2023 FLOT1 promotes gastric cancer progression and metastasis through BCAR1/ERK signaling. International journal of biological sciences 15 37928269
2018 The interaction of p130Cas with PKN3 promotes malignant growth. Molecular oncology 15 30422386
2015 Inhibition of Cycloartenol Synthase (CAS) Function in Tobacco BY-2 Cells. Lipids 15 26033687
2015 Functional Analysis of a Carotid Intima-Media Thickness Locus Implicates BCAR1 and Suggests a Causal Variant. Circulation. Cardiovascular genetics 15 26276885