| 1995 |
Paxillin (PXN) and FAK both bind directly to the cytoplasmic domain of the beta1 integrin subunit in vitro; the N-terminal non-catalytic domain of FAK recognizes integrin sequences distinct from those bound by alpha-actinin, and paxillin binding is independent of FAK binding despite overlapping integrin sequences, establishing that integrins can simultaneously recruit both signaling molecules. |
In vitro binding assay using GST-fusion peptides mimicking beta1 integrin cytoplasmic domain, pull-down from chicken embryo cell lysates |
The Journal of cell biology |
High |
7657702
|
| 1996 |
The LIM3 domain of PXN is the principal determinant of focal adhesion localization; vinculin binding maps to residues 143–164 (a single site), while FAK binding requires residues 143–164 plus a second site at 265–313; mutation E151Q abolishes vinculin binding without affecting FAK binding, demonstrating separable interaction interfaces on paxillin. |
Truncation and point-mutation mutagenesis, transfection of GFP-tagged constructs into CHO.K1 fibroblasts, co-immunoprecipitation, immunofluorescence localization |
The Journal of cell biology |
High |
8922390
|
| 1999 |
The paxillin LD4 motif serves as a selective docking site for a complex containing PAK, PIX (a Rac GEF), and Nck, bridged by a novel 95-kDa ARF-GAP protein p95PKL (paxillin-kinase linker) that binds directly to LD4 and to PIX; disruption of this interaction (via LD4 deletion mutant or microinjection of GST-LD4) inhibits lamellipodia formation and cell migration, placing paxillin upstream of Rac-mediated actin cytoskeletal remodeling. |
Yeast two-hybrid, co-immunoprecipitation, GST pull-down, microinjection of GST-LD4 into NIH3T3 cells, wound-healing assay, GFP-p95PKL localization |
The Journal of cell biology |
High |
10330411
|
| 2000 |
Activation of EphA2 by ephrin-A1 recruits phosphatase SHP2 to EphA2 within one minute, leading to rapid dephosphorylation of both FAK and paxillin and dissociation of the FAK–EphA2 complex, demonstrating that Eph receptor signaling negatively regulates integrin–FAK–paxillin signaling. |
Co-immunoprecipitation, western blot with phospho-specific antibodies, time-course stimulation assay in intact cells |
Nature cell biology |
High |
10655584
|
| 2000 |
GIT1 (a GRK-interacting ARF-GAP) directly binds paxillin via its C-terminal 125-residue domain; overexpression of GIT1 displaces paxillin from focal complexes and promotes cell motility; this activity is regulated by PIX, and GIT1 also couples to FAK via its Spa2 homology domain, placing the GIT1–PIX–PAK–paxillin complex as a coordinator of focal complex disassembly. |
Co-immunoprecipitation, overexpression in fibroblasts and epithelial cells, immunofluorescence, domain-deletion mapping |
Molecular and cellular biology |
High |
10938112
|
| 2003 |
JNK1 directly phosphorylates paxillin on serine 178 both in vitro and in intact cells; expression of the phosphorylation-deficient S178A mutant of paxillin causes cells to form stable focal adhesions and impairs rapid cell migration in wound-healing assays, demonstrating that JNK1-mediated phosphorylation of paxillin is required for maintaining labile adhesions during rapid cell migration. |
In vitro kinase assay, site-directed mutagenesis (S178A), transfection into NBT-II and other cell lines, single-cell migration assay, wound-healing assay, immunofluorescence |
Nature |
High |
12853963
|
| 2011 |
Proteomic analysis of isolated focal adhesions revealed that paxillin (PXN) is a core component of the myosin-II-responsive focal adhesion proteome; its abundance in focal adhesions is enhanced by myosin-II-mediated contractility, and it participates in Rho-mediated focal adhesion maturation pathways. |
Affinity isolation of focal adhesions, quantitative mass spectrometry comparing focal adhesions ± myosin II inhibition (blebbistatin), SILAC proteomics |
Nature cell biology |
Medium |
21423176
|
| 2014 |
LSD1 (a histone demethylase) controls expression of paxillin (PXN) in androgen-independent prostate cancer cells; LSD1 depletion increases PXN mRNA and protein levels and leads to enhanced LPAR6 signaling, which promotes cell migration accompanied by phosphorylation of PXN; this identifies a LSD1–LPAR6–PXN axis controlling metastatic behavior. |
RNA-seq transcriptome analysis, ChIP-seq cistrome analysis, siRNA knockdown of LSD1, western blot for p-PXN, migration/invasion assays, in vivo mouse metastasis model |
Oncogenesis |
Medium |
25285406
|
| 2015 |
miR-212 directly targets the 3'UTR of PXN mRNA to suppress its expression; promoter hypermethylation silences miR-212 in gastric cancer, leading to PXN overexpression; restoration of miR-212 reduces PXN mRNA and protein and inhibits cell invasion and metastasis, while PXN re-expression rescues the miR-212-induced phenotype, establishing a methylation–miR-212–PXN axis in gastric cancer invasion. |
Luciferase 3'UTR reporter assay, RT-PCR, western blot, methylation analysis (5-aza treatment), transfection gain/loss-of-function, in vitro invasion assay, in vivo xenograft rescue experiment |
American journal of cancer research |
Medium |
26693054
|
| 2017 |
Nobiletin inhibits tumor angiogenesis in ER+ breast cancer cells by suppressing Src/FAK/STAT3 signaling, with PXN acting as a downstream target; EMSA and ChIP assays demonstrated that nobiletin blocks STAT3 binding to a novel binding site in the PXN gene promoter, reducing PXN transcription. |
Western blotting, RT-PCR, EMSA, ChIP assay, HUVEC tube formation assay, migration/invasion assays |
International journal of molecular sciences |
Medium |
28468300
|
| 2017 |
Paxillin (PXN) is a multifunctional focal adhesion scaffold phosphorylated on Tyr31, Tyr118, Ser188, and Ser190 upon integrin engagement; ERK-mediated phosphorylation of Ser106, Ser231, and Ser290 promotes paxillin disassembly from focal adhesions; the phosphatase PEST binds phosphorylated paxillin to drive disassembly; paxillin coordinates spatiotemporal Cdc42, Rac1, and RhoA GTPase activation by recruiting GEFs, GAPs, and GITs to focal adhesions. |
Synthesis/review of experimental literature including phospho-specific western blot, mutagenesis, co-immunoprecipitation studies compiled across multiple primary studies |
Journal of hematology & oncology |
Medium |
28214467
|
| 2018 |
PXN knockdown in cervical cancer cells suppresses Bcl-2 expression, induces apoptosis, and resensitizes cells to radiation, establishing PXN as a regulator of Bcl-2-dependent survival and radioresistance. |
siRNA knockdown of PXN, western blot for Bcl-2, colony formation assay, apoptosis assay, in vitro radiation sensitivity assay, in vivo xenograft |
Future oncology |
Low |
29318915
|
| 2018 |
Cytoplasmic LIF (leukemia inhibitory factor, resulting from signal peptide mutations) promotes nasopharyngeal carcinoma invasion and vascular dissemination by activating YAP1, which in turn modulates FAK/paxillin (PXN) signaling; pharmaceutical inhibition with AZD0530 (Src/FAK inhibitor) reverses LIF-mediated dissemination and promotes cytoplasmic YAP1 accumulation while suppressing focal adhesion kinase activity. |
Immunohistochemistry of NPC biopsies, immunofluorescence, western blot, SNV sequencing of LIF signal peptide, pharmacological inhibition (AZD0530), in vivo invasion and dissemination models |
Nature communications |
Medium |
30504771
|
| 2019 |
ETV4 transcription factor directly upregulates PXN transcription in non-small cell lung cancer; luciferase reporter assays confirmed direct regulatory effect of ETV4 on the PXN promoter; PXN knockdown partially abolished ETV4-induced cell proliferation and migration, placing PXN as a functional downstream effector of ETV4-driven tumorigenesis. |
Microarray analysis, luciferase reporter assay, gain/loss-of-function (siRNA, overexpression), migration and proliferation assays, in vivo xenograft |
Molecular carcinogenesis |
Medium |
31670855
|
| 2020 |
Talin-1 overexpression promotes gastric cancer cell migration and invasion through the PTK2(FAK)–PXN–VCL–E-Cadherin–CAPN2–MAPK1 signaling axis; siRNA knockdown and overexpression of Talin-1 modulate PXN protein levels and downstream effectors. |
Western blot, immunohistochemistry, Transwell migration/invasion assay, overexpression and knockdown in MKN-45 cells |
Journal of clinical laboratory analysis |
Low |
32951272
|
| 2020 |
miR-216b directly targets the 3'UTR of PXN, reducing its expression; miR-216b overexpression suppresses gastric cancer cell proliferation, migration and invasion; re-expression of PXN rescues these phenotypes; the miR-216b–PXN axis partially regulates PI3K/AKT signaling in gastric cancer cells. |
Luciferase 3'UTR reporter assay, western blot, gain/loss-of-function transfection, MTT, Transwell, flow cytometry, in vivo xenograft |
Pathology, research and practice |
Medium |
33422779
|
| 2021 |
Matrix stiffness activates FAK and paxillin (PXN) phosphorylation at focal adhesions in endothelial cells, promoting transition of Rac1 from inactive to active state; this in turn activates YAP nuclear translocation, driving endothelial tip cell specification; phospho-PXN also loosens intercellular connections to facilitate tip cell emergence. This defines a p-PXN–Rac1–YAP mechanotransduction axis. |
Tunable hydrogel substrates, immunofluorescence, western blot for p-FAK and p-PXN, Rac1 activation assay, YAP localization imaging, EC spheroid sprouting assay, siRNA knockdown |
Bioactive materials |
Medium |
34466738
|
| 2021 |
ITGB1 (integrin β1) drives hepatocellular carcinoma cell cycle progression through a signaling cascade involving PXN and YWHAZ (14-3-3ζ), with downstream AKT activation; ITGB1 knockdown by siRNA reduces PXN and YWHAZ protein expression, delays cell cycle progression, and impairs HCC aggressive behavior. |
Bioinformatics, siRNA knockdown, western blot, immunostaining, cell migration assay, drug resistance assay, colony formation, cell cycle analysis, xenograft |
Frontiers in cell and developmental biology |
Low |
34977001
|
| 2021 |
miR-497 targets CDC42 and ITGB1 mRNAs; miR-497 overexpression decreases CDC42 and ITGB1 and inhibits phosphorylation of FAK, paxillin (PXN), and AKT; CDC42 restoration counteracts miR-497-mediated inhibition of focal adhesion and GC metastasis, placing PXN phosphorylation downstream of the miR-497/CDC42/ITGB1/FAK axis. |
RT-PCR, western blot for p-PXN, p-FAK, p-AKT, miR-497 knockout mice (NMU-induced GC model), gain/loss-of-function, in vivo metastasis assay |
Molecular therapy. Nucleic acids |
Medium |
34589278
|
| 2023 |
ULK1 and ULK2 directly phosphorylate paxillin (PXN) at S32 and S119; this phosphorylation weakens homotypic PXN interactions and liquid-liquid phase separation of PXN, impairing focal adhesion assembly; ULK1/2 activity consequently reduces actin stress fiber assembly and focal adhesion formation, impeding cell contraction and migration independent of autophagy; ULK1/2 and FAK/Src have opposing effects on PXN and compete for phosphorylation of adjacent serine and tyrosine residues. |
In vitro kinase assay, site-directed mutagenesis (S32A/S119A), co-immunoprecipitation, FRAP, phase separation assay, focal adhesion immunofluorescence, traction force microscopy, breast cancer cell migration assay, ULK1/2 knockout cells |
EMBO reports |
High |
37846507
|
| 2023 |
ANGPTL4 binding to the NRP1 receptor activates ABL1 tyrosine kinase, which phosphorylates paxillin (PXN), promoting HNSCC tumor cell migration; siRNA silencing of NRP1 or ABL1, or treatment with the ABL1 inhibitor dasatinib, blocks PXN phosphorylation and cell migration, identifying NRP1/ABL1/PXN as a signaling axis downstream of ANGPTL4 in head and neck squamous cell carcinoma. |
Co-IP, siRNA knockdown of NRP1 and ABL1, pharmacological inhibition (dasatinib), western blot for p-PXN, migration assay, orthotopic HNSCC tumor model |
Cellular signalling |
Medium |
37169211
|
| 2024 |
CXCL5 activates phosphorylation of the Paxillin/AKT signaling cascade in lung cancer cells, leading to upregulation of PD-L1 expression through a positive feedback loop; combined anti-CXCL5 and anti-PD-L1 treatment inhibits tumor growth in vivo, with PXN phosphorylation serving as a mechanistic link between CXCL5 signaling and immune checkpoint upregulation. |
Western blot for p-PXN and p-AKT, gene silencing (siRNA), flow cytometry for PD-L1, confocal immunofluorescence, in vivo SCID/NOD mouse xenograft, ELISA |
Journal of experimental & clinical cancer research |
Medium |
39034411
|
| 2025 |
The disordered N-terminal domain of paxillin (PXN) undergoes significant compaction upon binding the FAK focal adhesion targeting domain (FAT), forming a flexible 48-kDa multi-modal complex with four major interconverting conformational states; each state involves unique sets of contacts from disordered PXN regions that are highly conserved; shifts in this multi-state equilibrium via ligand binding or phosphorylation may rewire cellular signaling networks. |
NMR spectroscopy, small-angle X-ray scattering (SAXS), ensemble modeling, structural validation of the PXN N-domain–FAT complex |
bioRxivpreprint |
High |
|
| 2025 |
Knockdown of PXN in premalignant Src-activated mammary epithelial cells prevents the transient increase in tensile forces at focal adhesions, which in turn abolishes the build-up of tensile forces at adherens junctions and suppresses cell proliferation; this demonstrates that PXN-dependent FA tension is required upstream of AJ strengthening and EGFR-ERK/MRTF-A-SRF activation during early malignant progression. |
siRNA knockdown of PXN, FRET-based tension sensors at focal adhesions and adherens junctions, immunofluorescence, proliferation assay, in vivo Drosophila E-cadherin knockdown model |
bioRxivpreprint |
Medium |
|
| 2025 |
STAT3 directly upregulates PXN transcription in GBM; PXN reciprocally activates STAT3 by regulating SRC transcription, forming a positive feedback loop; additionally, PXN stabilizes the YB-1 protein by inhibiting its ubiquitin-mediated proteasomal degradation, and this YB-1 stabilization contributes to GBM malignancy through multiple downstream pathways. |
qRT-PCR, western blot, immunohistochemistry, ChIP assay (STAT3 on PXN promoter), mRNA sequencing, co-immunoprecipitation (PXN–YB-1), ubiquitination assay, siRNA/overexpression functional assays |
Cell death discovery |
Medium |
41872167
|