| 2020 |
Layilin (LAYN) colocalizes with integrin αLβ2 (LFA-1) on CD8+ T cells, and cross-linking layilin promotes the activated/extended state of LFA-1. LAYN deletion results in attenuated LFA-1-dependent cellular adhesion, and lineage-specific deletion of layilin on murine CD8+ T cells reduced their accumulation in tumors and increased tumor growth in vivo. Gene editing of LAYN in human CD8+ T cells reduced direct tumor cell killing ex vivo. |
Colocalization microscopy, cross-linking experiments, integrin activation assay, CRISPR gene editing in human T cells, conditional knockout in mice with tumor growth readout |
The Journal of experimental medicine |
High |
32539073
|
| 2021 |
Layilin expression on Tregs is induced by TCR-mediated activation in the presence of IL-2 or TGF-β. In vivo, layilin expression on Tregs exerts a cumulative anchoring/motility-limiting effect, reducing Treg dynamic motility in tissue. Conditional deletion of layilin in Tregs reduced their accumulation in tumors but paradoxically enhanced immune regulation (increased tumor growth), without affecting Treg activation or suppressive capacity in vitro. |
Conditional knockout mice (Treg-specific LAYN deletion), live in vivo motility imaging, in vitro Treg suppression assay, flow cytometry, TCR activation experiments with cytokine stimulation |
Journal of immunology (Baltimore, Md. : 1950) |
High |
34470859
|
| 2015 |
Layilin (LAYN) is involved in TNF-α-induced epithelial-mesenchymal transformation (EMT) of renal tubular epithelial cells. TNF-α (but not TGF-β) upregulates LAYN expression, and knockdown of LAYN in KMRC-1 cells prevents TNF-α-induced vimentin upregulation, E-cadherin downregulation, and fibroblast-like morphological change. TGF-β-induced EMT was not affected by LAYN knockdown, indicating specificity to the TNF-α pathway. |
siRNA knockdown, qPCR, western blotting, immunocytochemistry, in vivo TNF-α administration in mice |
Biochemical and biophysical research communications |
Medium |
26410531
|
| 2014 |
Antibody-mediated cross-linking of the extracellular domain of layilin (LAYN) on chondrosarcoma cells enhances secretion of inflammatory factors IL-8 and complement C5/C5a. TNF-α upregulates LAYN expression in human articular chondrocytes. These findings establish LAYN as a receptor whose signaling promotes inflammatory mediator secretion in chondrocytes. |
Anti-LAYN antibody stimulation of extracellular domain, ELISA for cytokine secretion, qPCR, western blotting |
Biochemical and biophysical research communications |
Medium |
25150153
|
| 2012 |
LAYN functions as a hyaluronan (HA) receptor in human articular chondrocytes. HA represses IL-1β-induced MMP-1 and MMP-13 production in chondrocytes, and this effect is significantly abrogated when LAYN is knocked down by siRNA, placing LAYN as a mediator of HA's anti-inflammatory/chondroprotective signaling. IL-1β suppresses LAYN expression in chondrocytes and synoviocytes. |
siRNA knockdown, ELISA for MMP-1 and MMP-13, IL-1β and TNFα stimulation experiments, in vitro cell culture |
Modern rheumatology |
Medium |
22722918
|
| 2023 |
In colorectal cancer cells, hyaluronan oligosaccharides (oHA) activate LAYN by binding to the 60–68th amino acid region of its extracellular segment. oHA-induced LAYN activation promotes cancer cell metastasis and CCL20 secretion through the NF-κB pathway. A blocking antibody targeting LAYN prevents oHA-mediated tumor metastasis, tumor-associated macrophage (TAM) infiltration, and M2 macrophage polarization in vivo. |
Domain mapping (extracellular segment mutagenesis/binding assay), NF-κB pathway reporter, CCL20 ELISA, blocking antibody experiments, in vitro and in vivo metastasis assays |
Matrix biology : journal of the International Society for Matrix Biology |
Medium |
36805871
|
| 2024 |
CREB1 binds to the LAYN promoter (validated by chromatin immunoprecipitation) and transcriptionally regulates LAYN expression. LAYN interacts with TLN1 (talin-1) as demonstrated by co-immunoprecipitation. The LAYN-TLN1 axis promotes β1 integrin signaling, including phosphorylation of c-Jun, p38 MAPK, and ERK, driving cholangiocarcinoma metastasis. Knockdown of LAYN suppressed EMT and metastasis in vivo in a nude mouse model. |
Chromatin immunoprecipitation (ChIP), co-immunoprecipitation (Co-IP), western blot, KD/OE cell lines, CCK-8 and Transwell assays, nude mouse tail vein metastasis model, immunofluorescence |
Heliyon |
Medium |
39286102
|
| 2011 |
LAYN was identified as a downstream effector of the p53-p21 and p16-pRB tumour suppressor pathways in mediating cellular senescence. Direct silencing of LAYN using lentiviral shRNAmirs bypassed senescence in conditionally immortalised human fibroblasts in which these pathways were activated. |
RNA interference screen, lentiviral shRNAmir knockdown, microarray expression profiling, conditional senescence induction system |
BMC genomics |
Medium |
21740549
|
| 2015 |
Knockdown of LAYN in human Tregs or overexpression in conventional T cells (Tconvs) affects Treg suppression activity in an in vitro human Treg suppression assay, implicating LAYN in the suppressive function of Tregs. |
siRNA knockdown in human Tregs, overexpression in Tconvs, in vitro suppression assay |
Human immunology |
Low |
26686412
|
| 2022 |
LAYN expression on CD8+ T cells is transcriptionally regulated by the upstream transcription factor NR4A1. Overexpression of LAYN in CD8+ T cells inhibited their killing function against tumor cells in co-culture. Low-dose anti-VEGFR2 antibody treatment downregulated LAYN expression on tumor-infiltrating CD8+ T cells, correlating with enhanced anti-tumor immunity. |
CD8+ T cell overexpression of LAYN, co-culture tumor killing assay, flow cytometry, in vivo anti-VEGFR2 treatment, NR4A1 transcription factor analysis |
Cellular oncology (Dordrecht, Netherlands) |
Low |
36260222
|
| 2023 |
Layilin/LAYN protein is expressed in the apical membrane regions or throughout motile cilia of multiciliated cells (MCCs), but is absent from primary cilia. LAYN silencing altered apical actin cap formation and multiciliogenesis in human, mouse, and pig MCC models, indicating a functional role in MCC formation. |
Single-cell RNA-seq, super-resolution microscopy, siRNA knockdown with multiciliogenesis phenotype readout |
FEBS letters |
Medium |
37102425
|
| 2021 |
Adhesion of invasive breast cancer cells (MDA-MB-231) to bone marrow-derived mesenchymal stem cells (bmMSCs) is facilitated by a tumor-cell-induced HA-rich matrix and is mediated by the HA receptor LAYN, as demonstrated in co-culture adhesion experiments. |
Co-culture adhesion assay, HA matrix manipulation, identification of LAYN as mediator of adhesion |
Scientific reports |
Low |
34707175
|