Affinage

LASP1

LIM and SH3 domain protein 1 · UniProt Q14847

Length
261 aa
Mass
29.7 kDa
Annotated
2026-04-28
100 papers in source corpus 38 papers cited in narrative 38 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

LASP1 is a multidomain actin-binding scaffold protein that coordinates cytoskeletal dynamics, cell migration, and nuclear signaling through phosphorylation-regulated shuttling between focal adhesions and the nucleus. Its LIM domain, nebulin-repeat actin-binding region, and SH3 domain mediate direct interactions with F-actin (Kd ~2 µM), zyxin, palladin-140kDa, N-WASP/Arp2/3, Krp1, and FAK at focal contacts, podosomes, and lamellipodia, where it is required for zyxin recruitment, pseudopodial elongation, podosome-mediated matrix degradation, and cell migration (PMID:9848085, PMID:15004028, PMID:16430883, PMID:22514729, PMID:32704133). PKA phosphorylation at Ser146 reduces F-actin binding affinity and triggers ZO-2-dependent nuclear import (with CRM1-mediated export and PP2B-dependent cytoplasmic return), while Src/BCR-ABL phosphorylation at Tyr171 regulates focal adhesion targeting and Ago2 binding to modulate Let-7a-guided RNAi (PMID:12432067, PMID:22665060, PMID:19718473, PMID:32872485). In the nucleus, LASP1 serves as a scaffold for the UHRF1/DNMT1/G9a/Snail1 epigenetic silencing complex and interacts with eIF4A/eIF4B to promote cap-dependent translation of oncogenic mRNAs, linking CXCR4/CXCL12 chemokine signaling to both epigenetic reprogramming and translational control (PMID:25982273, PMID:31106142).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1995 High

    Identification of LASP1 as the founding member of a novel LIM-SH3 protein subfamily established its unique domain architecture and predicted dual scaffolding capability.

    Evidence cDNA cloning and domain analysis from breast cancer overexpression screen

    PMID:7589475

    Open questions at the time
    • No function assigned beyond domain prediction
    • Binding partners unknown
    • Subcellular localization not determined
  2. 1998 High

    Demonstrating that LASP1 directly binds F-actin in vitro and co-localizes with actin at cell extensions, while undergoing Src-dependent tyrosine phosphorylation, established it as a regulated actin-associated protein rather than a purely transcriptional LIM factor.

    Evidence In vitro actin-binding assay, confocal microscopy, c-Src-transformed fibroblasts

    PMID:9688835 PMID:9848085

    Open questions at the time
    • Actin-binding domain not mapped to specific residues
    • Functional consequence of Src phosphorylation undefined
    • Role in cell motility not yet tested
  3. 2002 High

    Quantitative binding studies showed PKA phosphorylation at Ser99/Ser146 reduces F-actin affinity, and mutagenesis linked these sites to cAMP-dependent intracellular translocation, revealing phosphorylation as a molecular switch controlling LASP1 subcellular distribution.

    Evidence Actin pull-down with His-tagged wild-type and phosphomimetic LASP1, PKA in vitro phosphorylation, parietal cell transfection

    PMID:12432067

    Open questions at the time
    • Nuclear translocation not yet recognized
    • Identity of the phosphatase reversing the switch unknown
    • Downstream effectors of translocation uncharacterized
  4. 2004 High

    Multiple studies converged to show LASP1 is required for cell migration (not adhesion), localizes to focal complexes and pseudopodia tips, interacts with zyxin via its SH3 domain, and is phosphorylated at Tyr171 by c-Abl upon apoptotic stimuli — establishing it as a migration-promoting scaffold regulated by multiple kinases.

    Evidence siRNA knockdown with migration assay, yeast two-hybrid and co-precipitation for zyxin, c-Abl kinase assay with Y171 mutagenesis, phosphopeptide mapping

    PMID:15004028 PMID:15138294 PMID:15465019

    Open questions at the time
    • Mechanism by which LASP1 promotes migration beyond zyxin recruitment unclear
    • Whether Y171 and S146 phosphorylation are coordinated unknown
    • In vivo genetic validation lacking
  5. 2006 High

    Epistasis experiments showed LASP1 knockdown displaces zyxin from focal contacts without reciprocal dependency, and 140-kDa palladin recruits LASP1 to stress fibers via an SH3-binding motif, establishing a hierarchical scaffold network at adhesion sites.

    Evidence Reciprocal siRNA of LASP1 and zyxin with immunofluorescence; yeast two-hybrid and isoform-specific siRNA for palladin

    PMID:16430883 PMID:16492705

    Open questions at the time
    • Whether palladin and zyxin interactions are simultaneous or competitive unknown
    • Structural basis of non-canonical SH3 binding not resolved
  6. 2008 High

    Lasp1 knockout mice exhibited enhanced gastric acid secretion, providing the first in vivo genetic evidence that LASP1 negatively regulates H+,K+-ATPase trafficking in parietal cells through its actin-regulatory function.

    Evidence Lasp1 gene knockout mouse, in vivo gastric acid measurement, aminopyrine accumulation in isolated glands

    PMID:18483181

    Open questions at the time
    • Mechanism of H+,K+-ATPase trafficking regulation not molecularly resolved
    • Whether other organ systems are affected in knockout not systematically characterized
  7. 2009 High

    Src phosphorylation at Y171 was shown to drive LASP1 translocation to focal contacts in thrombin-stimulated platelets downstream of integrin αIIbβ3, while Krp1 crystal structure revealed a β-propeller presenting two LASP1-binding sites required for pseudopodial elongation — broadening LASP1's role beyond epithelial cells.

    Evidence Src inhibitors and Y171 mutagenesis in platelets; crystal structure of Krp1 C-terminal domain plus peptide array mapping

    PMID:19718473 PMID:19726686

    Open questions at the time
    • Whether Y171 phosphorylation affects the same pool as S146-phosphorylated LASP1 unknown
    • Platelet-specific LASP1 knockout phenotype not reported
  8. 2012 High

    The complete nuclear shuttling mechanism was elucidated: PKA phosphorylation at S146 triggers LASP1/ZO-2 complex nuclear import, CRM1 mediates export via a nuclear export signal, and PP2B dephosphorylation returns LASP1 to focal contacts — explaining earlier observations of nuclear LASP1 in cancer.

    Evidence Co-IP, proximity ligation assay, leptomycin B treatment, phosphomimetic/phospho-dead mutants, nuclear fractionation

    PMID:22665060

    Open questions at the time
    • Functional consequence of nuclear LASP1 not yet identified
    • Whether ZO-2 is the sole nuclear import carrier unknown
  9. 2015 High

    Nuclear LASP1 was found to scaffold the UHRF1/DNMT1/G9a/Snail1 epigenetic silencing complex in a CXCR4/CXCL12-dependent manner, providing the first function for nuclear LASP1 and linking chemokine signaling to epigenetic reprogramming.

    Evidence Proteomic analysis of LASP1 immunoprecipitates, co-IP, proximity ligation assay, CXCR4 antagonist AMD-3100

    PMID:25982273

    Open questions at the time
    • Target genes silenced by this complex not identified
    • Whether LASP1 is catalytically active or purely structural in the complex unknown
    • Stoichiometry and assembly order not determined
  10. 2019 High

    LASP1 was shown to directly bind eIF4A and eIF4B components of the translation initiation complex and to modulate cap-dependent translation of oncogenic mRNAs including BIRC5, revealing a cytoplasmic function in translational control beyond its cytoskeletal roles.

    Evidence GST pull-down, proximity ligation assay, co-IP, 5'UTR luciferase reporter for eIF4A-dependent translation

    PMID:31106142

    Open questions at the time
    • Full translatome regulated by LASP1 not defined
    • Whether this function requires phosphorylation at specific sites unknown
    • Relationship between cytoskeletal and translational functions unclear
  11. 2020 High

    Two additional effector arms were defined: LASP1 binds N-WASP to stimulate Arp2/3-dependent actin polymerization promoting CRC invasion, and LASP1 directly binds Ago2 in a phosphorylation-dependent manner to modulate Let-7a-guided RNAi activity and CCR7 expression.

    Evidence Yeast two-hybrid, co-IP, actin polymerization assay, xenograft for N-WASP; GST pull-down with phospho-mutants, PLA, Let-7a target analysis for Ago2

    PMID:32704133 PMID:32872485

    Open questions at the time
    • Whether N-WASP and Ago2 interactions compete for the same LASP1 pool unknown
    • Broader miRNA repertoire affected by LASP1-Ago2 not characterized
    • In vivo validation of Ago2 interaction lacking
  12. 2021 High

    LASP1 was identified as a component of the Cadherin-11/β-Catenin complex at cell-cell contacts in fibroblast-like synoviocytes, and Lasp1 deletion in TNF-transgenic mice reduced arthritic joint destruction, establishing a role in inflammatory joint disease pathology.

    Evidence Co-IP, siRNA/antibody blocking, PDGF response assay, Lasp1 knockout crossed to hTNF-transgenic arthritis model

    PMID:34131132

    Open questions at the time
    • Whether LASP1 directly binds Cadherin-11 or β-Catenin or is recruited indirectly not resolved
    • Mechanism by which LASP1 loss reduces joint destruction at the molecular level unclear
  13. 2022 Medium

    Post-translational regulation of LASP1 was expanded beyond phosphorylation: HBX-induced SUMOylation via RANBP2/RANGAP1 stabilizes HER2 by preventing its ubiquitination, and TRIM15-mediated K63-linked ubiquitination of LASP1 promotes its nuclear translocation and TKI resistance.

    Evidence Co-IP, SUMOylation assay, K63-linkage-specific ubiquitination assay, nuclear fractionation, TKI resistance assay

    PMID:36473530 PMID:36670097

    Open questions at the time
    • SUMOylation sites on LASP1 not mapped
    • Whether SUMOylation and K63-ubiquitination are coordinated or mutually exclusive unknown
    • Both findings from single labs without independent replication

Open questions

Synthesis pass · forward-looking unresolved questions
  • A comprehensive structural model of full-length LASP1 in complex with its key partners, the precise gene targets of the nuclear LASP1-epigenetic complex, and the in vivo physiological consequences of LASP1 loss beyond gastric acid secretion and arthritis remain to be determined.
  • No full-length crystal or cryo-EM structure of LASP1
  • Target gene repertoire of the UHRF1/DNMT1/G9a/Snail1-LASP1 complex undefined
  • Comprehensive phenotyping of Lasp1 knockout across organ systems not reported

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 10 GO:0060090 molecular adaptor activity 6
Localization
GO:0005856 cytoskeleton 11 GO:0005634 nucleus 6 GO:0005829 cytosol 5 GO:0005886 plasma membrane 4
Pathway
R-HSA-162582 Signal Transduction 6 R-HSA-392499 Metabolism of proteins 6 R-HSA-1500931 Cell-Cell communication 3 R-HSA-4839726 Chromatin organization 2 R-HSA-1474244 Extracellular matrix organization 1
Partners
ACTA1AGO2KRT80PALLDPTK2TJP2WASLZYX
Complex memberships
Cadherin-11/β-Catenin complexUHRF1/DNMT1/G9a/Snail1 epigenetic complexeIF4F translation initiation complex

Evidence

Reading pass · 38 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 LASP1 (MLN50/Lasp-1) was identified as the founding member of a new LIM protein subfamily, characterized by an N-terminal LIM motif and a C-terminal SH3 domain, encoded by a 261-residue protein. cDNA cloning and domain analysis FEBS letters High 7589475
1996 The N-terminal zinc-binding module of the LASP1 LIM domain was resolved by NMR spectroscopy; zinc is coordinated by Cys5, Cys8, His26, and Cys29, establishing the N-terminal half of a LIM domain as an independent folding unit. 1H NMR spectroscopy and energy-refined conformer calculation Biochemistry High 8841116
1998 LASP1 contains a functional actin-binding domain in the core of the protein; it binds actin in vivo and in vitro, co-localizes with actin at peripheral cell extensions, and is tyrosine-phosphorylated in Src-transformed fibroblasts. In vitro actin-binding assay, confocal immunofluorescence, transfection in c-SrcY527F-transformed cells Molecular medicine High 9848085
1998 LASP1 (pp40) is a cAMP-dependent phosphoprotein substrate of PKA in gastric parietal cells; forskolin stimulation produces a higher-molecular-weight phosphorylated form, and the protein contains conserved PKA consensus sequences. Protein isolation, microsequencing, cDNA cloning, Western blot, Northern blot, forskolin stimulation The American journal of physiology High 9688835
2000 Histamine-induced cAMP elevation in gastric parietal cells increases LASP1 phosphorylation and causes partial redistribution of LASP1 from the cell cortex (where it co-localizes with γ-actin) to the β-actin-enriched intracellular canalicular region, the site of active proton transport. Immunofluorescence, subcellular fractionation, cAMP stimulation assay in parietal cells Journal of cell science High 10806114
2002 LASP1 binds non-muscle F-actin in vitro with Kd ~2 µM (saturation ~1:7); PKA phosphorylation at Ser99 and Ser146 increases the Kd and decreases Bmax, reducing F-actin binding affinity. Alanine substitution at these sites suppresses cAMP-dependent translocation to the intracellular canalicular region in parietal cells. Actin pull-down assay with bacterially expressed His-tagged LASP1, site-directed mutagenesis, PKA phosphorylation in vitro, parietal cell transfection Journal of cell science High 12432067
2004 LASP1 localizes to focal complexes and the leading edge of pseudopodia in migratory cells and is required for cell migration (but not adhesion) in response to growth factors and ECM proteins. c-Abl kinase phosphorylates LASP1 at tyrosine 171 upon apoptotic stimulation, causing loss of focal adhesion localization and induction of cell death. Large-scale proteomic analysis of pseudopodia, siRNA knockdown, immunofluorescence, c-Abl kinase assay, site-directed mutagenesis The Journal of cell biology High 15138294
2004 LASP1 interacts with zyxin via its SH3 domain; the SH3 domain is necessary and sufficient for zyxin binding. The binding site in zyxin is at its extreme N-terminus and does not contain a classical PXXP sequence. LASP1 and zyxin co-localize at focal adhesions. Co-precipitation, yeast two-hybrid, site-directed mutagenesis of zyxin N-terminus The Journal of biological chemistry High 15004028
2004 Mouse LASP1 is phosphorylated in intact cells specifically at threonine 156 by PKA and PKG; in vitro PKA/PKG can also phosphorylate Ser61 and Ser99. Forskolin induces translocation of LASP1 from focal contacts to the cell interior. Overlay studies show LASP1 directly binds proline-rich domains of zyxin, LPP, and VASP (zyxin being the most prominent partner); LASP1 exists as a monomer. In vitro kinase assay, phosphopeptide mapping, immunofluorescence, overlay assay, gel filtration Biochemical and biophysical research communications High 15465019
2004 LASP1 is a component of CNS postsynaptic densities and is concentrated at synaptic sites and dendritic spines in neurons. MudPIT proteomic analysis of purified postsynaptic fractions, immunofluorescence Journal of neuroscience research Medium 15372503
2006 LASP1 silencing in breast cancer cells arrests cells in G2/M phase, reduces proliferation and migration; overexpression in non-tumor PTK-2 cells increases motility. LASP1 knockdown reduces zyxin binding to focal contacts without altering actin stress fibers, whereas zyxin silencing does not affect LASP1 localization, indicating LASP1 is required for recruiting zyxin to focal contacts. siRNA knockdown, cell cycle analysis, wound-healing assay, immunofluorescence Experimental cell research High 16430883
2006 The 140 kDa isoform of palladin (but not 90 kDa) directly binds LASP1 via an SH3-domain binding motif, confirmed by yeast two-hybrid and GST pull-down assays. Isoform-specific siRNA experiments show 140 kDa palladin recruits LASP1 to stress fibers. Yeast two-hybrid, GST pull-down, isoform-specific siRNA, immunofluorescence Journal of cell science High 16492705
2007 LASP1 is not exclusively cytosolic; it is also detectable in the nucleus of breast cancer cells as confirmed by Western blot of nuclear/cytosolic fractionations and confocal microscopy. Nuclear LASP1 localization correlates with increased tumor size and nodal positivity. Nuclear/cytosolic fractionation Western blot, confocal immunofluorescence microscopy BMC cancer Medium 17956604
2008 Targeted disruption of Lasp1 in mice results in enhanced histamine-stimulated HCl secretion in parietal cells, indicating that Lasp1 negatively regulates parietal cell acid secretion, likely by modulating trafficking/activation of the H+,K+-ATPase proton pump through cAMP-dependent phosphorylation-regulated actin interactions. Lasp1 gene knockout mouse model, in vivo gastric acid secretion measurement, [14C]aminopyrine accumulation in isolated gastric glands American journal of physiology. Gastrointestinal and liver physiology High 18483181
2008 p53 transcriptionally represses LASP1 via a p53 response element in the LASP1 promoter; wild-type p53 (but not DNA-binding mutants) suppresses LASP1 in p53-null cells, while p53 siRNA upregulates LASP1 in p53-expressing cells. Transient transfection, luciferase reporter assay, siRNA, site-directed mutagenesis of p53 DNA-binding residues Journal of hepatology High 19155088
2009 LASP1 is a downstream effector of urokinase-type plasminogen activator (uPA) in hepatocellular carcinoma; uPA silencing by RNAi reduces LASP1 expression, and ectopic uPA overexpression increases LASP1, with both proteins affecting cell motility. LASP1 depletion disrupts actin microfilament organization. 2D-DIGE proteomics, MALDI-TOF-MS identification, Western blot, immunofluorescence, siRNA knockdown Neoplasia Medium 19177205
2009 Kelch-related protein 1 (Krp1) directly interacts with LASP1 in membrane ruffles at the tips of pseudopodia; two specific binding sites on Krp1 (amino acids 317-327 and 563-574) are brought into proximity by a novel six-bladed β-propeller structure. Both sites are necessary for Krp1-LASP1 interaction in vitro and for pseudopodial elongation in vivo. Peptide array probing with recombinant LASP1, mutational analysis, crystal structure of Krp1 C-terminal domain, immunofluorescence The Journal of biological chemistry High 19726686
2009 Src kinase phosphorylates LASP1 at tyrosine 171 in thrombin-stimulated platelets; fibrinogen-mediated integrin αIIbβ3 activation triggers this phosphorylation, which promotes LASP1 translocation from cytosol to focal contacts and leading lamellae, indicating a role in platelet cytoskeleton rearrangement. Src-specific inhibitors, site-directed mutagenesis (Y171), immunofluorescence of adherent platelets and CHO cell model Thrombosis and haemostasis High 19718473
2012 LASP1 nuclear import is regulated by PKA-dependent phosphorylation at serine 146, which induces translocation of the LASP1/ZO-2 complex from cytoplasm to nucleus. Interaction occurs between the C-terminal proline-rich motif of ZO-2 and the SH3 domain of LASP1. Nuclear export is mediated by CRM1 and a newly identified nuclear export signal in LASP1. Dephosphorylation by PP2B relocalizes LASP1 back to focal contacts. Co-IP, in situ proximity ligation assay, nuclear/cytosolic fractionation, CRM1 inhibitor (leptomycin B), phosphomimetic/phospho-dead mutants Oncogene High 22665060
2012 LASP1 is a novel component of podosomes, localizing to the podosome ring structure (co-localizing with zyxin and vinculin), and is recruited during early podosome assembly. LASP1 knockdown in human macrophages impairs podosome dynamics and matrix degradation capacity. Immunofluorescence, live cell imaging, siRNA knockdown, matrix degradation assay PloS one High 22514729
2014 LASP1 is a direct substrate of BCR-ABL oncogenic kinase in CML; BCR-ABL specifically phosphorylates LASP1 at tyrosine 171, which is abolished by tyrosine kinase inhibitor therapy. Phospho-LASP1-Y171 binds to non-phosphorylated CRKL at its SH2 domain, disrupting normal CRKL regulation. Phosphoproteomic mass spectrometry, in vitro kinase assay, co-IP, tyrosine kinase inhibitor treatment of CML patients Oncotarget High 24913448
2014 LASP1 overexpression in pancreatic ductal adenocarcinoma is mediated by HIF1α, which directly binds a hypoxia response element in the LASP1 promoter, promoting LASP1 expression in vitro and in mouse xenografts. ChIP assay, luciferase reporter assay, HIF1α knockdown/overexpression, xenograft tumor model Cancer research High 25385028
2015 Nuclear LASP1 acts as a hub for an epigenetic complex comprising UHRF1, DNMT1, G9a, and the transcription factor Snail1. CXCL12-activated CXCR4 signaling drives nuclear translocation of LASP1, which then associates with UHRF1, G9a, Snail1, and di/tri-methylated histone H3 in a CXCL12-dependent manner. LASP1 directly binds Snail1, potentially stabilizing it. Proteomic analysis of LASP1 immunoprecipitates, co-IP, proximity ligation assay, CXCR4 antagonist AMD-3100, 3D Matrigel culture Oncogene High 25982273
2016 LASP1 interacts with S100A11 and enhances its expression, driving TGFβ-mediated epithelial-mesenchymal transition in colorectal cancer. LASP1-S100A11 axis operates through downstream effectors flotillin-1 (cytoplasmic) and histone H1 (nuclear). Co-IP, subcellular fractionation, siRNA knockdown, xenograft assay Scientific reports Medium 27181092
2016 LASP1 regulates expression and secretion of MMP1, MMP3, and MMP9 in invasive breast cancer cells. LASP1 depletion reduces AP-1 transcriptional activity, which controls MMP expression. LASP1 also promotes MMP secretion into the extracellular matrix. Microarray analysis, Western blot, luciferase reporter assay for AP-1 activity, zymography, rescue experiments Oncotarget Medium 27588391
2017 LASP1 directly interacts with FAK and facilitates phosphorylation of FAK at Tyr397, which in turn promotes AKT phosphorylation at Ser473, promoting non-small cell lung cancer proliferation and invasion. FAK inhibition abolishes AKT phosphorylation but not vice versa, placing FAK upstream of AKT in the LASP1 pathway. Co-IP, Western blot with phospho-specific antibodies, FAK/AKT inhibitors, epistasis by sequential inhibitor treatment Oncotarget Medium 29088849
2017 LASP1 is transcriptionally activated by the transcription factor SOX9, which binds a consensus site in the LASP1 promoter, as demonstrated by luciferase reporter and ChIP assays. SOX9 knockdown phenocopies LASP1 knockdown effects on lung cancer cell proliferation and apoptosis. Luciferase reporter assay, ChIP assay, siRNA knockdown of SOX9 and LASP1 International journal of oncology Medium 29138807
2019 LASP1 interacts with components of the eIF4F translation initiation complex (eIF4A and eIF4B) in a CXCL12-dependent manner. LASP1 directly binds eIF4A and eIF4B (demonstrated by GST pull-down). Genetic silencing of LASP1 impairs eIF4A-dependent translation of oncogenic mRNAs (including BIRC5), and reduces sensitivity to Rocaglamide A. Proteomic screen, proximity ligation assay, co-IP, GST pull-down, 5'UTR luciferase reporter assay Frontiers in oncology High 31106142
2019 LASP1 interacts with PTEN, promotes PTEN ubiquitination and degradation, thereby activating the PI3K/AKT signaling pathway in nasopharyngeal carcinoma. LASP1 and PTEN co-localize in NPC cells. Co-IP, ubiquitination assay, immunofluorescence co-localization, rescue experiments with PTEN overexpression Cell death & disease Medium 29531214
2019 HBx upregulates LASP1 transcription through activation of c-Jun (AP-1) via the PI3K/JNK signaling pathway. HBx interacts with phosphorylated c-Jun in HCC cells, and ChIP assay demonstrates HBx binds to the LASP1 promoter together with c-Jun. The N-terminus of HBx is responsible for c-Jun activation. Luciferase reporter assay, ChIP assay, co-IP, PI3K/JNK inhibitors, N-terminal deletion constructs of HBx Journal of cellular physiology Medium 29600594
2020 LASP1 interacts with N-WASP (identified by yeast two-hybrid screen); N-WASP activates the Arp2/3 complex to stimulate actin polymerization, promoting CRC cell migration and invasion. LASP1 interaction with N-WASP does not alter N-WASP expression but rescues Arp2/3-dependent actin polymerization when N-WASP is silenced. Yeast two-hybrid screen, co-IP, actin polymerization assay, in vivo xenograft models Oncogene High 32704133
2020 CXCR4-activated LASP1 associates with Argonaute 2 (Ago2) in a CXCL12-dependent manner. LASP1 directly binds Ago2 through its LIM and SH3 domains (GST pull-down). Phosphorylation at S146 and Y171 of LASP1 dictates this binding. The LASP1-Ago2 interaction modulates Let-7a-guided RNAi activity and affects levels of Let-7a targets including CCR7. Co-IP, proximity ligation assay, GST pull-down, phospho-dead/phosphomimetic mutants, CXCR4 antagonist AMD3465, Let-7a target expression analysis Cancers High 32872485
2020 Nuclear LASP1, driven by CXCR4 activation, stabilizes nuclear Snail1 by upregulating nuclear pS473-Akt, pS9-GSK-3β, A20, and LSD1, and directly associating with Snail1, A20, GSK-3β, and LSD1. LASP1 ablation mislocalizes Snail1 and impairs Matrigel invasion. Co-IP of endogenous proteins, proximity ligation assay, CXCR4 antagonist, nuclear fractionation Western blot, Matrigel invasion assay Cancers Medium 32825729
2021 LASP1 functions as a binding partner of the Cadherin-11/β-Catenin complex at zipper-like cell-to-cell contacts in fibroblast-like synoviocytes. Loss or blocking of LASP1 alters pathological tissue formation, migratory behavior, and PDGF response of arthritic FLS. Deletion of Lasp1 in human TNF transgenic mice reduces arthritic joint destruction. Integrative epigenomic profiling, co-IP, siRNA/antibody blocking, PDGF response assay, Lasp1 knockout in TNF-transgenic arthritis mouse model Nature communications High 34131132
2021 METTL14 improves LASP1 mRNA stability through m6A modification, thereby activating the LASP1/SRC/AKT signaling axis and promoting fibroblast-like synoviocyte activation in rheumatoid arthritis. LASP1 overexpression reverses the effects of METTL14 knockdown on FLS migration, invasion, and cytokine production. shRNA knockdown of METTL14, Western blot for LASP1/p-SRC/p-AKT, rescue experiments with LASP1 overexpression, RA rat model American journal of physiology. Cell physiology Medium 36878846
2022 HBX promotes LASP1 SUMOylation via RANBP2 and RANGAP1 (which interact with LASP1), increasing LASP1 SUMOylation to stabilize HER2 by preventing its ubiquitination-mediated proteasomal degradation, thereby activating insulin signaling and enhancing HCC cell growth and migration. Co-IP, ubiquitination assay, SUMOylation assay, LASP1/HER2 interaction analysis, identification of RANBP2/RANGAP1 as LASP1 interactors International journal of biological macromolecules Medium 36473530
2023 TRIM15 mediates K63-linked polyubiquitination of LASP1, which promotes LASP1 nuclear translocation in hepatocellular carcinoma, increasing AKT phosphorylation and Snail expression to confer TKI resistance. This is regulated by the AKT/FOXO1 axis controlling TRIM15 expression. Co-IP, ubiquitination assay (K63 linkage-specific), Western blot for nuclear fractionation, FOXO1/AKT pathway analysis, TKI resistance assay Cell death & disease Medium 36670097
2017 LASP1 expression is negatively regulated by androgen receptor (AR) at the transcriptional level in prostate cancer; AR suppression elevates LASP1, while AR activation decreases it. LASP1 promotes cell cycle progression through cyclin D1 upregulation, and in vivo antisense oligonucleotide knockdown of LASP1 inhibits CRPC xenograft tumor growth. TMA analysis after hormone deprivation, AR gain/loss-of-function, cyclin D1 Western blot, cell cycle flow cytometry, in vivo ASO treatment of xenografts The Prostate Medium 27775154

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2012 MicroRNA-203 suppresses cell proliferation and migration by targeting BIRC5 and LASP1 in human triple-negative breast cancer cells. Journal of experimental & clinical cancer research : CR 170 22713668
1995 Lasp-1 (MLN 50) defines a new LIM protein subfamily characterized by the association of LIM and SH3 domains. FEBS letters 131 7589475
2004 Regulation of cell migration and survival by focal adhesion targeting of Lasp-1. The Journal of cell biology 119 15138294
2007 Overexpression of LASP-1 mediates migration and proliferation of human ovarian cancer cells and influences zyxin localisation. British journal of cancer 107 17211471
2006 Silencing of LASP-1 influences zyxin localization, inhibits proliferation and reduces migration in breast cancer cells. Experimental cell research 106 16430883
2002 Lasp-1 binds to non-muscle F-actin in vitro and is localized within multiple sites of dynamic actin assembly in vivo. Journal of cell science 105 12432067
2004 Zyxin interacts with the SH3 domains of the cytoskeletal proteins LIM-nebulette and Lasp-1. The Journal of biological chemistry 97 15004028
2014 Tumor-suppressive microRNA-218 inhibits cancer cell migration and invasion via targeting of LASP1 in prostate cancer. Cancer science 94 24815849
2010 Functional role of LASP1 in cell viability and its regulation by microRNAs in bladder cancer. Urologic oncology 94 20843712
2019 ANLN-induced EZH2 upregulation promotes pancreatic cancer progression by mediating miR-218-5p/LASP1 signaling axis. Journal of experimental & clinical cancer research : CR 92 31395079
2014 LASP1 is a HIF1α target gene critical for metastasis of pancreatic cancer. Cancer research 91 25385028
2006 Identification of palladin isoforms and characterization of an isoform-specific interaction between Lasp-1 and palladin. Journal of cell science 91 16492705
1998 Lasp-1, a novel type of actin-binding protein accumulating in cell membrane extensions. Molecular medicine (Cambridge, Mass.) 81 9848085
2000 The LIM and SH3 domain-containing protein, lasp-1, may link the cAMP signaling pathway with dynamic membrane restructuring activities in ion transporting epithelia. Journal of cell science 73 10806114
1998 Lasp-1 is a regulated phosphoprotein within the cAMP signaling pathway in the gastric parietal cell. The American journal of physiology 73 9688835
2015 An update on the LIM and SH3 domain protein 1 (LASP1): a versatile structural, signaling, and biomarker protein. Oncotarget 69 25622104
2007 Nuclear localization and cytosolic overexpression of LASP-1 correlates with tumor size and nodal-positivity of human breast carcinoma. BMC cancer 69 17956604
2016 LASP1-S100A11 axis promotes colorectal cancer aggressiveness by modulating TGFβ/Smad signaling. Scientific reports 65 27181092
2010 Role of LIM and SH3 protein 1 (LASP1) in the metastatic dissemination of medulloblastoma. Cancer research 64 20924110
2012 miR-203 inhibits the migration and invasion of esophageal squamous cell carcinoma by regulating LASP1. International journal of oncology 60 22940702
2014 Loss of tumor suppressor mir-203 mediates overexpression of LIM and SH3 Protein 1 (LASP1) in high-risk prostate cancer thereby increasing cell proliferation and migration. Oncotarget 59 24980827
2004 Phosphorylation of mouse LASP-1 on threonine 156 by cAMP- and cGMP-dependent protein kinase. Biochemical and biophysical research communications 58 15465019
2016 The tumor-suppressive function of miR-1 by targeting LASP1 and TAGLN2 in esophageal squamous cell carcinoma. Journal of gastroenterology and hepatology 57 26414725
2008 LIM and SH3 protein 1 (Lasp1) is a novel p53 transcriptional target involved in hepatocellular carcinoma. Journal of hepatology 57 19155088
2010 Nuclear localisation of LASP-1 correlates with poor long-term survival in female breast cancer. British journal of cancer 56 20461080
2017 Upregulation of the long non-coding RNA PVT1 promotes esophageal squamous cell carcinoma progression by acting as a molecular sponge of miR-203 and LASP1. Oncotarget 53 28404954
2021 HSP90-dependent PUS7 overexpression facilitates the metastasis of colorectal cancer cells by regulating LASP1 abundance. Journal of experimental & clinical cancer research : CR 51 33990203
2012 Nuclear import of LASP-1 is regulated by phosphorylation and dynamic protein-protein interactions. Oncogene 51 22665060
2017 MiR-203a-3p suppresses cell proliferation and metastasis through inhibiting LASP1 in nasopharyngeal carcinoma. Journal of experimental & clinical cancer research : CR 49 28982387
1996 Solution structure of a naturally-occurring zinc-peptide complex demonstrates that the N-terminal zinc-binding module of the Lasp-1 LIM domain is an independent folding unit. Biochemistry 46 8841116
2017 Hypoxia-inducible microRNA-218 inhibits trophoblast invasion by targeting LASP1: Implications for preeclampsia development. The international journal of biochemistry & cell biology 44 28412444
2017 COPS5 and LASP1 synergistically interact to downregulate 14-3-3σ expression and promote colorectal cancer progression via activating PI3K/AKT pathway. International journal of cancer 44 29226323
2003 The human LASP1 gene is fused to MLL in an acute myeloid leukemia with t(11;17)(q23;q21). Oncogene 44 12527918
2016 Epigenetically regulated miR-145 suppresses colon cancer invasion and metastasis by targeting LASP1. Oncotarget 43 27626692
2015 LASP-1: a nuclear hub for the UHRF1-DNMT1-G9a-Snail1 complex. Oncogene 43 25982273
2017 MicroRNA-133a acts as a tumour suppressor in breast cancer through targeting LASP1. Oncology reports 40 29207145
2018 New Frontiers for the Cytoskeletal Protein LASP1. Frontiers in oncology 39 30298118
2016 LASP-1 induces proliferation, metastasis and cell cycle arrest at the G2/M phase in gallbladder cancer by down-regulating S100P via the PI3K/AKT pathway. Cancer letters 39 26797416
2016 Regulation of matrix metalloproteinases (MMPs) expression and secretion in MDA-MB-231 breast cancer cells by LIM and SH3 protein 1 (LASP1). Oncotarget 39 27588391
2018 LASP1 promotes nasopharyngeal carcinoma progression through negatively regulation of the tumor suppressor PTEN. Cell death & disease 36 29531214
2004 Actin-binding proteins in a postsynaptic preparation: Lasp-1 is a component of central nervous system synapses and dendritic spines. Journal of neuroscience research 36 15372503
2021 ECHS1, an interacting protein of LASP1, induces sphingolipid-metabolism imbalance to promote colorectal cancer progression by regulating ceramide glycosylation. Cell death & disease 34 34615856
2019 Long non-coding RNA MIAT promotes papillary thyroid cancer progression through upregulating LASP1. Cancer cell international 34 31372094
2016 Proteomic profiling of lung adenocarcinoma indicates heightened DNA repair, antioxidant mechanisms and identifies LASP1 as a potential negative predictor of survival. Clinical proteomics 34 27799870
2019 Hsa_circ_0004370 promotes esophageal cancer progression through miR-1294/LASP1 pathway. Bioscience reports 33 30988074
2017 Lasp1 promotes malignant phenotype of non-small-cell lung cancer via inducing phosphorylation of FAK-AKT pathway. Oncotarget 33 29088849
2015 Molecular characterization of LASP-1 expression reveals vimentin as its new partner in human hepatocellular carcinoma cells. International journal of oncology 33 25760690
2012 Role of hepatitis B virus X protein in regulating LIM and SH3 protein 1 (LASP-1) expression to mediate proliferation and migration of hepatoma cells. Virology journal 32 22897902
2020 Knockdown of circular RNA circ-FARSA restricts colorectal cancer cell growth through regulation of miR-330-5p/LASP1 axis. Archives of biochemistry and biophysics 31 32473899
2016 Loss of the 14-3-3σ is essential for LASP1-mediated colorectal cancer progression via activating PI3K/AKT signaling pathway. Scientific reports 31 27156963
2012 Lasp-1 regulates podosome function. PloS one 31 22514729
2020 Up-regulated microRNA-218-5p ameliorates the damage of dopaminergic neurons in rats with Parkinson's disease via suppression of LASP1. Brain research bulletin 30 33144090
1998 Chromosomal assignment and expression pattern of the murine Lasp-1 gene. Gene 28 9511759
2018 LASP1 promotes glioma cell proliferation and migration and is negatively regulated by miR-377-3p. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 27 30372896
2020 LINC01123 Promotes the Progression of Colorectal Cancer via miR-625-5p/LASP1 Axis. Cancer biotherapy & radiopharmaceuticals 26 32423238
2020 LINC01503/miR-342-3p facilitates malignancy in non-small-cell lung cancer cells via regulating LASP1. Respiratory research 26 32938459
2012 Overexpression of LASP1 is associated with proliferation, migration and invasion in esophageal squamous cell carcinoma. Oncology reports 26 23254782
2008 Targeted disruption of the Lasp-1 gene is linked to increases in histamine-stimulated gastric HCl secretion. American journal of physiology. Gastrointestinal and liver physiology 26 18483181
2021 Lasp1 regulates adherens junction dynamics and fibroblast transformation in destructive arthritis. Nature communications 25 34131132
2023 METTL14 promotes fibroblast-like synoviocytes activation via the LASP1/SRC/AKT axis in rheumatoid arthritis. American journal of physiology. Cell physiology 24 36878846
2019 Long Noncoding RNA SNHG16 Sponges miR-182-5p And miR-128-3p To Promote Retinoblastoma Cell Migration And Invasion By Targeting LASP1. OncoTargets and therapy 24 31806989
2009 Proteomic identification of LASP-1 down-regulation after RNAi urokinase silencing in human hepatocellular carcinoma cells. Neoplasia (New York, N.Y.) 24 19177205
2009 Novel beta-propeller of the BTB-Kelch protein Krp1 provides a binding site for Lasp-1 that is necessary for pseudopodial extension. The Journal of biological chemistry 24 19726686
2020 miR-133 inhibits proliferation and promotes apoptosis by targeting LASP1 in lupus nephritis. Experimental and molecular pathology 23 31987844
2016 MicroRNA-218 inhibits the proliferation, migration, and invasion and promotes apoptosis of gastric cancer cells by targeting LASP1. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 23 27696291
2015 LASP-1, regulated by miR-203, promotes tumor proliferation and aggressiveness in human non-small cell lung cancer. Experimental and molecular pathology 23 26683818
2020 LASP1 interacts with N-WASP to activate the Arp2/3 complex and facilitate colorectal cancer metastasis by increasing tumour budding and worsening the pattern of invasion. Oncogene 22 32704133
2020 MicroRNA-184 negatively regulates corneal epithelial wound healing via targeting CDC25A, CARM1, and LASP1. Eye and vision (London, England) 22 32766356
2020 MiR-133a acts as a tumor suppressor in lung cancer progression by regulating the LASP1 and TGF-β/Smad3 signaling pathway. Thoracic cancer 22 33074595
2020 LASP1 induces colorectal cancer proliferation and invasiveness through Hippo signaling and Nanog mediated EMT. American journal of translational research 22 33194046
2017 MicroRNA-133b Inhibits Proliferation, Cellular Migration, and Invasion via Targeting LASP1 in Hepatocarcinoma Cells. Oncology research 22 28117027
2016 MicroRNA-29a plays a suppressive role in non-small cell lung cancer cells via targeting LASP1. OncoTargets and therapy 21 27895492
2014 LASP1 is a novel BCR-ABL substrate and a phosphorylation-dependent binding partner of CRKL in chronic myeloid leukemia. Oncotarget 21 24913448
2012 LASP-1, a novel urinary marker for detection of bladder cancer. Urologic oncology 21 22481019
2012 Lasp1 is down-regulated in NMDA receptor antagonist-treated mice and implicated in human schizophrenia susceptibility. Journal of psychiatric research 21 23040864
2021 LASP1 Induces Epithelial-Mesenchymal Transition in Lung Cancer through the TGF-β1/Smad/Snail Pathway. Canadian respiratory journal 20 34912481
2019 The CXCR4-LASP1-eIF4F Axis Promotes Translation of Oncogenic Proteins in Triple-Negative Breast Cancer Cells. Frontiers in oncology 20 31106142
2019 LASP1 promotes proliferation, metastasis, invasion in head and neck squamous cell carcinoma and through direct interaction with HSPA1A. Journal of cellular and molecular medicine 20 31793711
2017 Paving the path for invasion: The polyedric role of LASP1 in cancer. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 20 28621232
2020 Role of the CXCR4-LASP1 Axis in the Stabilization of Snail1 in Triple-Negative Breast Cancer. Cancers 19 32825729
2022 Long non-coding RNA (lncRNA) CYTOR promotes hepatocellular carcinoma proliferation by targeting the microRNA-125a-5p/LASP1 axis. Bioengineered 18 35081873
2022 Hsa_circ_0007142 contributes to cisplatin resistance in esophageal squamous cell carcinoma via miR-494-3p/LASP1 axis. Journal of clinical laboratory analysis 18 35312115
2020 The CXCR4-Dependent LASP1-Ago2 Interaction in Triple-Negative Breast Cancer. Cancers 18 32872485
2017 LASP1 in Tumor and Tumor Microenvironment. Current molecular medicine 18 29473505
2009 Lasp1 gene disruption is linked to enhanced cell migration and tumor formation. Physiological genomics 18 19531578
2022 Hepatitis B virus X protein increases LASP1 SUMOylation to stabilize HER2 and facilitate hepatocarcinogenesis. International journal of biological macromolecules 17 36473530
2009 Integrin-dependent translocation of LASP-1 to the cytoskeleton of activated platelets correlates with LASP-1 phosphorylation at tyrosine 171 by Src-kinase. Thrombosis and haemostasis 17 19718473
2023 TRIM15 forms a regulatory loop with the AKT/FOXO1 axis and LASP1 to modulate the sensitivity of HCC cells to TKIs. Cell death & disease 16 36670097
2021 Flavopereirine Suppresses the Progression of Human Oral Cancer by Inhibiting the JAK-STAT Signaling Pathway via Targeting LASP1. Drug design, development and therapy 16 33935493
2021 Circular RNA hsa_circ_0033144 (CircBCL11B) regulates oral squamous cell carcinoma progression via the miR-579/LASP1 axis. Bioengineered 16 34288804
2019 Increased long noncoding RNA LASP1-AS is critical for hepatocellular carcinoma tumorigenesis via upregulating LASP1. Journal of cellular physiology 16 30677131
2023 Exosomal circCOL1A2 from cancer cells accelerates colorectal cancer progression via regulating miR-665/LASP1 signal axis. European journal of pharmacology 15 37059374
2018 HBX protein promotes LASP-1 expression through activation of c-Jun in human hepatoma cells. Journal of cellular physiology 14 29600594
2021 Long non‑coding RNA H19 regulates LASP1 expression in osteosarcoma by competitively binding to miR‑29a‑3p. Oncology reports 13 34328197
2020 hsa_circRNA_000166 Facilitated Cell Growth and Limited Apoptosis through Targeting miR-326/LASP1 Axis in Colorectal Cancer. Gastroenterology research and practice 13 33376485
2017 Role of LASP-1, a novel SOX9 transcriptional target, in the progression of lung cancer. International journal of oncology 13 29138807
2016 Upregulated LASP-1 correlates with a malignant phenotype and its potential therapeutic role in human cholangiocarcinoma. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 13 26729195
2016 Suppression of LIM and SH3 Domain Protein 1 (LASP1) Negatively Regulated by Androgen Receptor Delays Castration Resistant Prostate Cancer Progression. The Prostate 13 27775154
2006 Chromosomal assignment of LASP1 and LASP2 genes and organization of the LASP2 gene in chicken. Cytogenetic and genome research 13 16276103
2021 Circular RNA circ_0006948 Promotes Esophageal Squamous Cell Carcinoma Progression by Regulating microRNA-3612/LASP1 Axis. Digestive diseases and sciences 12 34024023