Affinage

LASP1

LIM and SH3 domain protein 1 · UniProt Q14847

Length
261 aa
Mass
29.7 kDa
Annotated
2026-06-10
100 papers in source corpus 44 papers cited in narrative 44 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

LASP1 is a multidomain actin-binding scaffold protein with an N-terminal LIM domain and a C-terminal SH3 domain that organizes the cortical cytoskeleton and couples it to signaling at focal adhesions, lamellipodia, and podosomes (PMID:7589475, PMID:9848085, PMID:22514729). The isolated LIM module folds as an independent zinc-coordinating rubredoxin-knuckle (PMID:8841116), while a central actin-binding region mediates direct, saturable binding to non-muscle F-actin (Kd ~2 µM) that is attenuated by PKA-dependent phosphorylation at S99/S146, controlling cAMP-driven translocation of LASP1 between the cortex and intracellular compartments in parietal cells (PMID:12432067). Through its SH3 domain LASP1 docks onto proline-rich and linear motifs in cytoskeletal partners—zyxin, the 140 kDa palladin isoform, Krp1/Kelch repeats, and N-WASP—positioning it upstream of zyxin recruitment to focal contacts and licensing N-WASP/Arp2/3-mediated actin polymerization to drive migration and invasion (PMID:15004028, PMID:16492705, PMID:19726686, PMID:32704133, PMID:17211471). Tyrosine phosphorylation at Y171 by Src-family and Abl-type kinases (including BCR-ABL) governs focal adhesion localization and creates a binding site for CRKL, linking LASP1 to oncogenic kinase signaling (PMID:15138294, PMID:19718473, PMID:24913448). LASP1 also shuttles to the nucleus as a PKA-S146-phosphorylated complex with ZO-2, exported via a Crm-1-dependent NES and recycled by PP2B (PMID:22665060); in a CXCR4/CXCL12-dependent manner nuclear LASP1 scaffolds the Snail1 stabilization and epigenetic machinery and associates with the eIF4F translation-initiation and Ago2/RISC complexes to control oncogenic gene expression (PMID:25982273, PMID:32825729, PMID:31106142, PMID:32872485). Its abundance is set transcriptionally—activated by HIF1α and c-Jun/AP-1 and repressed by p53—and its activity is further tuned by ubiquitin- and SUMO-dependent modifications (PMID:25385028, PMID:29600594, PMID:19155088, PMID:36670097, PMID:36473530). Physiologically, LASP1 acts as a negative regulator of parietal cell HCl secretion and, in fibroblast-like synoviocytes, binds Cadherin-11/β-Catenin complexes to drive arthritic joint destruction (PMID:18483181, PMID:34131132).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1996 High

    Established that the LASP1 LIM domain is a structurally autonomous zinc-binding module, defining the architectural basis of the protein.

    Evidence NMR solution structure of a synthetic ZF-1 peptide complexed with zinc

    PMID:8841116

    Open questions at the time
    • Structure limited to a 30-residue isolated module, not full-length protein
    • Functional role of zinc coordination in cells not tested
  2. 1998 Medium

    Defined LASP1 as an actin-binding protein and connected it to Src-family tyrosine kinase signaling, placing it at the cytoskeleton-signaling interface.

    Evidence In vitro actin-binding assays, confocal co-localization, and Western blot of c-Src-transformed fibroblasts

    PMID:9848085

    Open questions at the time
    • Actin-binding region not finely mapped
    • Functional consequence of tyrosine phosphorylation unresolved at this stage
  3. 2002 High

    Quantified direct F-actin binding and showed PKA phosphorylation at S99/S146 reduces affinity, providing a molecular switch for cAMP-driven LASP1 relocalization.

    Evidence Actin pull-down with recombinant LASP1, in vitro PKA phosphorylation, phospho-mutants, and parietal cell imaging

    PMID:12432067

    Open questions at the time
    • Structural basis of the actin interface not solved
    • Phospho-regulation studied mainly in parietal cells
  4. 2004 High

    Mapped the SH3 domain as the docking module for cytoskeletal partners and established LASP1 as required for migration but not adhesion, with Y171 phosphorylation controlling focal adhesion residency.

    Evidence Yeast two-hybrid, co-precipitation, mutagenesis of zyxin/palladin motifs, pseudopodial proteomics, and siRNA migration assays

    PMID:15004028 PMID:15138294 PMID:15465019 PMID:16492705

    Open questions at the time
    • Order of partner recruitment at focal contacts not fully resolved
    • Distinct contributions of zyxin vs palladin binding unclear
  5. 2008 High

    Genetic knockout established LASP1 as an in vivo negative regulator of parietal cell acid secretion, validating its physiological cytoskeletal-signaling role.

    Evidence Lasp-1 knockout mice with in vivo and ex vivo gastric acid secretion assays

    PMID:18483181

    Open questions at the time
    • Molecular mechanism linking LASP1 to the secretory machinery not defined
    • Whether effect is purely actin-dependent untested
  6. 2009 High

    Resolved the Krp1/Kelch binding interface structurally and confirmed Src/integrin-driven Y171 phosphorylation directs LASP1 to focal contacts in adherent cells.

    Evidence Crystal structure of Krp1 C-terminal β-propeller with peptide-array mapping, plus platelet adhesion and Y171 mutagenesis studies

    PMID:19718473 PMID:19726686

    Open questions at the time
    • Integration of multiple SH3 ligands at one focal contact not modeled
    • Kinase selectivity for Y171 across cell types unclear
  7. 2012 High

    Identified the nuclear shuttling mechanism, showing PKA-S146 phosphorylation drives a LASP1/ZO-2 complex into the nucleus with Crm-1-dependent export and PP2B-dependent recycling.

    Evidence Reciprocal co-IP, proximity ligation, phospho-mutants, leptomycin B export inhibition, and fractionation

    PMID:22665060

    Open questions at the time
    • Nuclear function downstream of import not defined in this study
    • Stoichiometry of nuclear LASP1/ZO-2 complex unknown
  8. 2015 Medium

    Revealed nuclear LASP1 as a CXCR4-dependent scaffold for the UHRF1-DNMT1-G9a epigenetic complex and Snail1, connecting cytoskeletal LASP1 to transcriptional/epigenetic control of EMT.

    Evidence Proteomics of LASP1 immunoprecipitates, PLA, endogenous co-IP, and CXCR4 antagonist blocking

    PMID:25982273

    Open questions at the time
    • Direct vs scaffold-mediated contacts within the complex not separated
    • Functional impact on DNA methylation marks not directly measured
  9. 2016 Medium

    Positioned LASP1 as a regulator of protein-stability and PI3K/AKT signaling through SH3-mediated binding to COPS5 and 14-3-3σ degradation, and as an AP-1-dependent driver of MMP expression.

    Evidence Yeast two-hybrid, GST pull-down, ubiquitination assays, AP-1 luciferase reporter, and zymography across CRC and breast cancer models

    PMID:27156963 PMID:27181092 PMID:27588391 PMID:29226323

    Open questions at the time
    • Whether LASP1 directly enables ubiquitin ligase activity or acts as adaptor unresolved
    • Cell-type generality of the 14-3-3σ axis untested
  10. 2020 Medium

    Extended nuclear LASP1's scaffolding role to the eIF4F translation-initiation complex and Ago2/RISC, with phosphorylation-state-dependent binding linking CXCR4 signaling to oncogenic translation and miRNA activity.

    Evidence Proteomic screens, PLA, endogenous co-IP, GST pull-down with phospho-mutants, 5'UTR reporters, and CXCR4 antagonist blocking

    PMID:31106142 PMID:32825729 PMID:32872485

    Open questions at the time
    • Direct RNA-binding capacity of LASP1 not demonstrated
    • How one scaffold partitions among actin, RISC, and eIF4F pools unknown
  11. 2021 High

    Defined a physiological non-cancer role by showing LASP1 binds Cadherin-11/β-Catenin junctions and drives arthritic joint destruction in vivo.

    Evidence Epigenomic profiling, co-IP for the Cadherin-11/β-Catenin/Lasp1 complex, and Lasp1 knockout in TNF transgenic arthritic mice

    PMID:34131132

    Open questions at the time
    • Mechanistic link between junctional LASP1 and FLS invasion incomplete
    • Relationship to LASP1's actin and nuclear functions in this context unclear
  12. 2023 Medium

    Showed that ubiquitin- and SUMO-dependent modifications and upstream transcriptional/epitranscriptomic inputs converge to control LASP1 abundance and nuclear translocation in disease.

    Evidence K63-linkage-specific ubiquitination assays (TRIM15), SUMOylation assays (HBX/RANBP2/RANGAP1), ChIP for HIF1α/c-Jun, and m6A/METTL14 stability analyses

    PMID:25385028 PMID:29600594 PMID:36473530 PMID:36670097 PMID:36878846

    Open questions at the time
    • Sites of K63-ubiquitination and SUMOylation on LASP1 not mapped
    • Direct m6A residues on LASP1 mRNA not demonstrated

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single scaffold dynamically partitions between F-actin, focal adhesions, the nucleus, RISC, and the translation machinery—and whether these pools are mutually exclusive or coordinated—remains unresolved.
  • No full-length LASP1 structure with bound partners
  • Quantitative flux between functional pools unmeasured
  • Causal hierarchy among phosphorylation, ubiquitination, and SUMOylation switches undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 4 GO:0008092 cytoskeletal protein binding 3 GO:0098772 molecular function regulator activity 3
Localization
GO:0005634 nucleus 3 GO:0005856 cytoskeleton 3 GO:0005829 cytosol 2
Pathway
R-HSA-1266738 Developmental Biology 3 R-HSA-162582 Signal Transduction 3 R-HSA-8953854 Metabolism of RNA 2
Partners
AGO2COPS5CRKLPALLDSNAI1WASLZO-2ZYX
Complex memberships
Ago2/RISCCadherin-11/β-Catenin complexUHRF1-DNMT1-G9a epigenetic complexeIF4F translation initiation complex

Evidence

Reading pass · 44 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 LASP1 (Lasp-1/MLN50) was identified as a new LIM protein subfamily member containing an N-terminal LIM motif and a C-terminal SH3 domain, defining a novel domain architecture. cDNA cloning and sequence analysis FEBS letters Medium 7589475
1996 The N-terminal zinc-binding module of the Lasp-1 LIM domain (residues 1-30) folds as an independent structural unit coordinating zinc via Cys5, Cys8, His26, and Cys29, adopting a rubredoxin-knuckle motif consistent with other LIM domain modules. 1H NMR solution structure determination of synthetic peptide ZF-1 complexed with zinc Biochemistry High 8841116
1998 Lasp-1 contains an 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 fibroblasts transformed by constitutively active c-Src (SrcY527F). In vitro actin-binding assay, in vivo co-localization by confocal microscopy, Western blot of Src-transformed fibroblasts Molecular medicine (Cambridge, Mass.) Medium 9848085
1998 Lasp-1 is a cAMP-dependent phosphoprotein in gastric parietal cells; stimulation of parietal cells, distal colonic crypts, and pancreatic cells with forskolin induces a higher-molecular-weight (phosphorylated) form of Lasp-1, placing it downstream of PKA in the cAMP signaling pathway. Microsequencing/cloning, Northern and Western blot, forskolin stimulation of isolated cells The American journal of physiology Medium 9688835
2000 In gastric parietal cells, histamine-induced elevation of cAMP increases Lasp-1 phosphorylation and induces partial redistribution of Lasp-1 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, histamine stimulation correlated with acid secretion assays Journal of cell science Medium 10806114
2002 Lasp-1 binds directly to non-muscle F-actin in vitro with apparent Kd ~2 µM and saturation stoichiometry ~1:7; PKA-dependent phosphorylation at S99 and S146 increases Kd and decreases Bmax, reducing actin-binding affinity. Phosphorylation-site alanine mutants (S99A/S146A) suppress cAMP-dependent translocation of Lasp-1 to the intracellular canalicular region in parietal cells. Actin pull-down assay with bacterially expressed His-Lasp-1, in vitro PKA phosphorylation, site-directed mutagenesis, parietal cell transfection and immunofluorescence Journal of cell science High 12432067
2003 LASP1 is a fusion partner of MLL in an infant AML with t(11;17)(q23;q21); the MLL/LASP1 fusion protein lacks in vitro myeloid progenitor transformation capability, placing it in a subgroup of non-transforming MLL fusions. FISH, RT-PCR, RACE cloning of fusion transcript, retroviral transduction of myeloid progenitors Oncogene Medium 12527918
2004 Lasp-1 localizes to focal complexes and the leading edge of pseudopodia in migrating cells. Growth factor or ECM stimulation causes Lasp-1 to relocalize from the cell periphery to the leading edge; c-Abl-mediated phosphorylation of Lasp-1 at tyrosine 171 (induced by apoptotic agents) causes loss of focal adhesion localization and cell death. Lasp-1 is required for cell migration but not adhesion. Large-scale pseudopodial proteomics, siRNA knockdown migration/adhesion assays, immunofluorescence, c-Abl kinase inhibitor experiments, phosphorylation mapping The Journal of cell biology High 15138294
2004 LASP-1 interacts with zyxin, LPP, and VASP via their proline-rich domains; zyxin is the most prominent partner. LASP-1 exists as a monomer despite its LIM domain. Mouse LASP-1 is phosphorylated by PKA and PKG in vitro at S61, S99, and T156, but only at T156 in intact cells; phosphorylation by either kinase causes translocation from focal contacts to the cell interior without affecting F-actin. Overlay binding assays, gel filtration (monomer determination), in vitro kinase assays with PKA/PKG, immunofluorescence of human and mouse mesangial cells treated with forskolin Biochemical and biophysical research communications Medium 15465019
2004 The SH3 domain of Lasp-1 is necessary and sufficient for interaction with zyxin; the binding site in zyxin is at its extreme N-terminus and uses a linear motif lacking the classical PXXP sequence. Co-precipitation and yeast two-hybrid confirmed the Lasp-1–zyxin interaction. Yeast two-hybrid, co-precipitation, site-directed mutagenesis of zyxin binding site The Journal of biological chemistry High 15004028
2004 Lasp-1 is a component of CNS postsynaptic densities and is concentrated at synaptic sites and dendritic spines of hippocampal neurons. MudPIT proteomics of purified postsynaptic fractions, immunofluorescence of CNS neurons Journal of neuroscience research Medium 15372503
2006 LASP-1 silencing in breast cancer cells causes G2/M arrest, suppresses proliferation by 30-50%, reduces migration by 50%, and reduces zyxin recruitment to focal contacts without altering actin stress fibers. Overexpression of LASP-1 in PTK-2 cells that lack endogenous LASP-1 increases cell motility. siRNA knockdown, cell cycle analysis, wound-healing assay, immunofluorescence, LASP-1 overexpression in LASP-1-negative cells Experimental cell research Medium 16430883
2006 The 140 kDa isoform of palladin (but not the 90 kDa isoform) directly binds Lasp-1 via its SH3-domain binding motif; isoform-specific siRNA of 140 kDa palladin reduces Lasp-1 recruitment to stress fibers. Yeast two-hybrid, GST pull-down, isoform-specific siRNA with immunofluorescence Journal of cell science High 16492705
2007 LASP-1 silencing in ovarian cancer cells arrests cells in G2/M, suppresses proliferation by 60-90%, reduces migration by 40%, and reduces zyxin binding to focal contacts. LASP-1 knockdown did not affect actin stress fiber or microtubule organization. Silencing zyxin did not affect LASP-1 expression or migration, placing LASP-1 upstream of zyxin at focal contacts. siRNA knockdown, cell cycle analysis, proliferation assay, migration assay, immunofluorescence for zyxin and actin British journal of cancer Medium 17211471
2007 LASP-1 is not exclusively cytosolic; it is also detectable in the nucleus of breast cancer cells, with nuclear accumulation correlating with higher tumor stage and increased proliferation (peak in G2/M phase). Confocal immunofluorescence, separate nuclear/cytosolic fractionation Western blots, cell synchronization experiments BMC cancer Medium 17956604
2008 Lasp-1 knockout mice show increased histamine-stimulated gastric HCl secretion compared to wild-type littermates, with slower inhibition by ranitidine, establishing Lasp-1 as a negative regulator of parietal cell acid secretion in vivo. Targeted gene disruption (knockout mouse), in vivo and ex vivo acid secretion assays, [14C]aminopyrine accumulation in isolated gastric glands American journal of physiology. Gastrointestinal and liver physiology High 18483181
2008 p53 transcriptionally represses LASP1 expression via a p53 response element in the LASP1 promoter; wild-type but not DNA-binding mutant p53 suppresses LASP1; p53 siRNA in p53-positive HepG2 cells upregulates LASP1. Luciferase reporter assay, transient transfection of WT and mutant p53 in p53-null cells, p53 siRNA, Western blot Journal of hepatology Medium 19155088
2009 Lasp-1 knockout mice display enhanced wound healing and more rapid tumor formation; Lasp-1-null MEFs migrate more rapidly in vitro, have more focal adhesions, and show increased LPP expression (~2-fold), suggesting LPP compensates for loss of Lasp-1 to enhance migration. Knockout mouse wound-healing assay, tumor initiation assay, MEF migration assay, focal adhesion counting, differential microarray analysis Physiological genomics Medium 19531578
2009 The Kelch repeats of Krp1 interact directly with Lasp-1 at two binding sites (residues 317-327 and 563-574) that are brought into proximity by a novel six-bladed β-propeller structure; both binding sites are required for Krp1-Lasp-1 interaction in vitro and for pseudopodial elongation in vivo. Peptide array overlay, recombinant Lasp-1 pulldown, mutational analysis, crystal structure of Krp1 C-terminal domain The Journal of biological chemistry High 19726686
2009 In thrombin-stimulated platelets, Lasp-1 undergoes tyrosine phosphorylation primarily by Src kinase at Y171; this phosphorylation is dependent on integrin αIIbβ3-fibrinogen engagement and correlates with translocation of Lasp-1 from the cytosol to focal contacts and the leading edge of spreading platelets. Src kinase inhibitor experiments, integrin-expressing CHO cell model, site-directed mutagenesis of Y171, immunofluorescence of adherent platelets Thrombosis and haemostasis Medium 19718473
2009 LASP-1 expression is downstream of urokinase (uPA) signaling in HCC cells; uPA upregulation increases LASP-1 expression, and LASP-1 siRNA shows involvement in actin microfilament organization. 2D-DIGE proteomics of uPA-siRNA-treated cells, MALDI-TOF-MS identification, Western blot and immunofluorescence confirmation, ectopic uPA and LASP-1 expression Neoplasia (New York, N.Y.) Medium 19177205
2012 Lasp-1 is a novel component of the podosome ring structure (co-localizing with zyxin and vinculin), is recruited during early podosome assembly, and its knockdown in macrophages impairs podosome dynamics and matrix degradation capacity. Immunofluorescence, live-cell imaging, siRNA knockdown in macrophages, matrix degradation assay PloS one Medium 22514729
2012 PKA phosphorylation of LASP-1 at S146 induces formation of a LASP-1/ZO-2 complex that translocates from cytoplasm to nucleus; the interaction occurs between the proline-rich C-terminal motif of ZO-2 and the SH3 domain of LASP-1. Nuclear export is Crm-1-dependent via a newly identified NES in LASP-1; dephosphorylation by PP2B relocalizes LASP-1 back to focal contacts. Co-immunoprecipitation, in situ proximity ligation assay, phosphorylation-site mutants, Crm-1 inhibitor (leptomycin B) experiments, nuclear/cytosolic fractionation Oncogene High 22665060
2014 LASP1 is a direct transcriptional target of HIF1α; HIF1α binds a hypoxia response element in the LASP1 promoter to upregulate LASP1 expression in pancreatic ductal adenocarcinoma cells in vitro and in mouse xenografts. ChIP assay demonstrating direct HIF1α binding to LASP1 promoter HRE, reporter assays, in vitro and xenograft overexpression/knockdown Cancer research Medium 25385028
2014 LASP1 is a direct substrate of BCR-ABL kinase in CML; BCR-ABL specifically phosphorylates LASP1 at Y171, abolished by TKI therapy. Phospho-LASP1-Y171 binds non-phosphorylated CRKL at its SH2 domain, linking BCR-ABL activity to CRKL signaling. Phosphoproteomic identification in CML patient samples, TKI treatment abolition, site-directed mutagenesis of Y171, co-immunoprecipitation of LASP1-CRKL complex Oncotarget Medium 24913448
2015 Nuclear LASP-1 associates with the epigenetic complex UHRF1-DNMT1-G9a and the transcription factor Snail1 in a CXCL12-dependent manner; LASP-1 directly binds Snail1 and may stabilize it. LASP-1 knockdown alters gene expression toward increased cell-junction and ECM proteins and changes cytokine secretion profile. Proteomic analysis of LASP-1 immunoprecipitates, proximity ligation assay validation, co-IP of endogenous proteins, 3D Matrigel culture, breast TMA immunohistochemistry, CXCR4 antagonist AMD-3100 blocking Oncogene Medium 25982273
2016 LASP1 interacts with S100A11; the LASP1-S100A11 axis is essential for TGFβ-mediated EMT and promotes colorectal cancer aggressiveness via downstream effectors flotillin-1 (cytoplasmic pathway) and histone H1 (nuclear pathway). Co-immunoprecipitation, gain- and loss-of-function assays, rescue experiments, xenograft models Scientific reports Medium 27181092
2016 LASP1 depletion in breast cancer cells downregulates MMP1, MMP3, and MMP9 expression and secretion; LASP1 regulates MMP transcription through AP-1 (c-Fos), as demonstrated by decreased AP-1 transcriptional activity in LASP1 knockdown cells by luciferase reporter assay. Microarray after LASP1 siRNA, Western blot confirmation, rescue experiments, AP-1 luciferase reporter assay, zymography Oncotarget Medium 27588391
2016 The SH3 domain of LASP1 directly binds the MPN domain of COPS5 (JAB1/CSN5); this interaction was confirmed by yeast two-hybrid and GST pull-down. LASP1 and COPS5 synergistically promote ubiquitination and degradation of 14-3-3σ, activating PI3K/AKT signaling in colorectal cancer. Yeast two-hybrid screening, GST pull-down, co-localization, gain/loss-of-function, ubiquitination assay, PI3K inhibitor rescue International journal of cancer Medium 29226323
2016 LASP1 interacts with 14-3-3σ and promotes its downregulation in colorectal cancer; loss of 14-3-3σ is required for LASP1-mediated AKT phosphorylation and CRC aggressiveness, placing 14-3-3σ as a direct downstream effector of LASP1. Proteomics identification plus co-IP validation, gain/loss-of-function, PI3K inhibitor rescue, co-localization Scientific reports Medium 27156963
2017 LASP1 directly binds FAK and facilitates phosphorylation of FAK at Tyr397 and AKT at Ser473 in NSCLC cells; FAK inhibition abrogates downstream AKT phosphorylation, but AKT inhibition does not affect FAK phosphorylation, establishing LASP1→FAK→AKT as a linear signaling axis. Co-immunoprecipitation, Western blot, FAK and AKT inhibitors, overexpression and knockdown in NSCLC cells Oncotarget Medium 29088849
2018 LASP1 interacts with and co-localizes with PTEN in NPC cells; LASP1 overexpression increases PTEN ubiquitination and decreases PTEN expression, thereby activating PI3K/AKT signaling. Co-immunoprecipitation, immunofluorescence co-localization, ubiquitination assay, rescue experiments with PTEN overexpression Cell death & disease Medium 29531214
2018 HBX promotes LASP-1 expression via activation of c-Jun (AP-1); HBX interacts with phosphorylated c-Jun and activates PI3K/JNK signaling; ChIP demonstrates direct binding of the HBX/c-Jun complex to the LASP-1 promoter AP-1 element. Luciferase reporter assay, ChIP assay, co-IP of HBX with p-c-Jun, PI3K/JNK inhibitor experiments, Western blot Journal of cellular physiology Medium 29600594
2019 LASP1 associates with components of the eIF4F translation initiation complex (eIF4A and eIF4B) in a CXCL12-dependent manner; LASP1 directly binds eIF4A and eIF4B via GST-pulldown; LASP1 knockdown impairs eIF4A-dependent translation of oncogenic mRNAs, and LASP1 deficiency sensitizes cells to eIF4A inhibitor Rocaglamide A. Proteomic screen, proximity ligation assay, co-immunoprecipitation, GST-pulldown, 5'UTR luciferase reporter assay, pharmacological eIF4A inhibition Frontiers in oncology Medium 31106142
2019 LASP1 interacts with HSPA1A (HSP70 family member) in HNSCC; HSPA1A acts as a chaperone for LASP1 and positively regulates LASP1-P-AKT interaction, enhancing malignant behavior. Co-immunoprecipitation, co-localization by immunofluorescence, gain/loss-of-function assays Journal of cellular and molecular medicine Low 31793711
2020 LASP1 interacts with N-WASP; this interaction does not alter N-WASP expression but rescues reduced actin polymerization caused by N-WASP silencing. N-WASP activates the Arp2/3 complex to promote actin polymerization and CRC cell migration/invasion. Yeast two-hybrid screening, co-immunoprecipitation confirmation, Arp2/3 actin polymerization assay, functional rescue experiments Oncogene Medium 32704133
2020 The CXCR4-LASP1 axis promotes nuclear accumulation and stabilization of Snail1 by upregulating nuclear pS473-Akt, pS9-GSK-3β, A20, and LSD1; LASP1 endogenously associates with Snail1, A20, GSK-3β, and LSD1 in a CXCL12-dependent manner. LASP1 ablation causes mislocalization of nuclear Snail1 and loss of Matrigel invasion. Co-immunoprecipitation, proximity ligation assay, nuclear/cytosolic fractionation Western blots, CXCR4 antagonist (AMD-3100) blocking, Matrigel invasion assay Cancers Medium 32825729
2020 LASP1 associates with Argonaute 2 (Ago2) endogenously in a CXCL12-dependent, CXCR4-mediated manner; LASP1 directly binds Ago2 through its LIM and SH3 domains via GST-pulldown; LASP1 phosphorylation status at S146 and Y171 determines binding. LASP1-Ago2 association modulates Let-7a-guided RISC activity and alters levels of Let-7a targets including CCR7. Co-immunoprecipitation (endogenous), proximity ligation assay, GST-pulldown with LASP1 phospho-mutants, CXCR4 antagonist (AMD3465) blocking, Let-7a target expression analysis Cancers Medium 32872485
2021 Lasp1 binds directly to Cadherin-11/β-Catenin complexes in fibroblast-like synoviocytes; loss or blocking of Lasp1 alters pathological tissue formation, migratory behavior, and PDGF response of arthritic FLS. In TNF transgenic arthritic mice, Lasp1 deletion reduces arthritic joint destruction. Epigenomic profiling, co-immunoprecipitation for Cadherin-11/β-Catenin/Lasp1 complex, Lasp1 knockout in TNF transgenic mice with histological and functional joint assessments, in vitro FLS functional assays Nature communications High 34131132
2021 LASP1 is identified as a sphingolipid-metabolism-involved protein by LC-MS; ECHS1 is identified as a new LASP1-interacting protein in CRC by protein interaction assay. LC-MS sphingolipid assay, protein interaction assay (co-IP), gain/loss-of-function in CRC cells Cell death & disease Low 34615856
2022 HBX increases LASP1 SUMOylation; SUMOylation is promoted by RANBP2 and RANGAP1 (which interact with LASP1) and enhances LASP1 binding to HER2, thereby preventing HER2 ubiquitination-mediated proteasomal degradation and stabilizing HER2 expression. Co-immunoprecipitation, SUMOylation assay, ubiquitination assay, Western blot for HER2 stability International journal of biological macromolecules Medium 36473530
2023 TRIM15 mediates K63-linked polyubiquitination of LASP1, promoting its nuclear translocation; nuclear LASP1 then increases AKT phosphorylation and Snail expression to drive TKI resistance in HCC. TRIM15 expression is regulated upstream by the AKT/FOXO1 axis. Western blot nuclear fractionation, co-immunoprecipitation, ubiquitination assay with K63-linkage specificity, gain/loss-of-function in HCC cells, pharmacological AKT/FOXO1 inhibition Cell death & disease Medium 36670097
2023 METTL14 stabilizes LASP1 mRNA through m6A modification, thereby promoting LASP1 protein expression and activating the SRC/AKT signaling axis in fibroblast-like synoviocytes; METTL14 knockdown reduces LASP1 expression and FLS activation. Western blot for LASP1, p-SRC, p-AKT after METTL14 shRNA; mRNA stability analysis with m6A modification; rescue by LASP1 overexpression; RA rat model American journal of physiology. Cell physiology Low 36878846
2015 LASP-1 overexpression in HCC cells, identified by MALDI-TOF mass spectrometry of co-immunoprecipitated fractions, reveals vimentin as a novel binding partner of LASP-1. Co-immunoprecipitation followed by MALDI-TOF mass spectrometry identification of vimentin International journal of oncology Low 25760690

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
2010 Functional role of LASP1 in cell viability and its regulation by microRNAs in bladder cancer. Urologic oncology 95 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 94 31395079
2014 Tumor-suppressive microRNA-218 inhibits cancer cell migration and invasion via targeting of LASP1 in prostate cancer. Cancer science 94 24815849
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 52 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
2021 ECHS1, an interacting protein of LASP1, induces sphingolipid-metabolism imbalance to promote colorectal cancer progression by regulating ceramide glycosylation. Cell death & disease 37 34615856
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
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
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 32 33144090
2016 Loss of the 14-3-3σ is essential for LASP1-mediated colorectal cancer progression via activating PI3K/AKT signaling pathway. Scientific reports 32 27156963
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
2012 Lasp-1 regulates podosome function. PloS one 31 22514729
1998 Chromosomal assignment and expression pattern of the murine Lasp-1 gene. Gene 28 9511759
2020 LINC01123 Promotes the Progression of Colorectal Cancer via miR-625-5p/LASP1 Axis. Cancer biotherapy & radiopharmaceuticals 27 32423238
2018 LASP1 promotes glioma cell proliferation and migration and is negatively regulated by miR-377-3p. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 27 30372896
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
2023 METTL14 promotes fibroblast-like synoviocytes activation via the LASP1/SRC/AKT axis in rheumatoid arthritis. American journal of physiology. Cell physiology 25 36878846
2021 Lasp1 regulates adherens junction dynamics and fibroblast transformation in destructive arthritis. Nature communications 25 34131132
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
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 23 32704133
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
2021 LASP1 Induces Epithelial-Mesenchymal Transition in Lung Cancer through the TGF-β1/Smad/Snail Pathway. Canadian respiratory journal 22 34912481
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
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 21 31793711
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
2019 The CXCR4-LASP1-eIF4F Axis Promotes Translation of Oncogenic Proteins in Triple-Negative Breast Cancer Cells. Frontiers in oncology 20 31106142
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
2022 Hsa_circ_0007142 contributes to cisplatin resistance in esophageal squamous cell carcinoma via miR-494-3p/LASP1 axis. Journal of clinical laboratory analysis 19 35312115
2020 Role of the CXCR4-LASP1 Axis in the Stabilization of Snail1 in Triple-Negative Breast Cancer. Cancers 19 32825729
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 18 36670097
2022 Long non-coding RNA (lncRNA) CYTOR promotes hepatocellular carcinoma proliferation by targeting the microRNA-125a-5p/LASP1 axis. Bioengineered 18 35081873
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 Exosomal circCOL1A2 from cancer cells accelerates colorectal cancer progression via regulating miR-665/LASP1 signal axis. European journal of pharmacology 16 37059374
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
2022 CERS6-AS1 Facilitates Oncogenesis and Restrains Ferroptosis in Papillary Thyroid Carcinoma by Serving as a ceRNA through miR-497-5p/LASP1 Axis. Annals of clinical and laboratory science 14 35777805
2018 HBX protein promotes LASP-1 expression through activation of c-Jun in human hepatoma cells. Journal of cellular physiology 14 29600594
2017 Role of LASP-1, a novel SOX9 transcriptional target, in the progression of lung cancer. International journal of oncology 14 29138807
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
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

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