| 2005 |
FRMD6/Willin contains a recognizable FERM domain at its N-terminus, is capable of binding phospholipids, and can co-localize with actin at the plasma membrane. Plasma membrane localization is not influenced by cytochalasin D-induced actin disruption but is induced by the addition of epidermal growth factor. |
Immunofluorescence/co-localization, cytochalasin D treatment, EGF stimulation, phospholipid binding assay |
FEBS letters |
Medium |
16137681
|
| 2011 |
Willin/FRMD6 activates the Hippo signaling pathway in mammalian cells: ectopic willin expression increases phosphorylation of MST1/2, LATS1, and YAP. This effect can be antagonized by ezrin. In MCF10A cells, willin overexpression antagonizes YAP activity via its N-terminal FERM domain. Loss of willin displays epithelial-to-mesenchymal transition features. |
Ectopic expression, Western blot for phosphorylated pathway components, FERM domain truncation constructs, knockdown with phenotypic readout |
Oncogene |
Medium |
21666719
|
| 2011 |
Willin/FRMD6 recruits aPKC and Par6 to the apical junctional complex (AJC) independently of Par3. Simultaneous depletion of Willin and Par3 removes aPKC/Par6 from AJCs and induces apical constriction via upregulation of AJC-associated ROCK levels. aPKC phosphorylates ROCK and suppresses its junctional localization, defining a Willin/Par3-aPKC-ROCK pathway controlling epithelial apical morphology. |
siRNA depletion (single and double knockdown), immunofluorescence, Western blot, genetic epistasis analysis in epithelial cells |
Nature cell biology |
High |
21685893
|
| 2012 |
Willin/FRMD6 binds to nectins (Ig-family adhesion proteins) at the apical junctional complex, and this binding is required for junctional recruitment of Willin. Nectin positioning at the AJC depends on afadin binding, placing the nectin-afadin interaction upstream of Willin localization. |
Co-immunoprecipitation, immunofluorescence, knockdown of nectins and afadin with Willin localization readout |
Genes to cells |
Medium |
22512338
|
| 2013 |
In mammalian sciatic nerve fibroblasts, Willin/FRMD6 is predominantly expressed and its expression activates the Hippo signaling cascade, inducing YAP translocation from nucleus to cytoplasm (Ser127 phosphorylation). Willin expression inhibits cellular proliferation but induces faster directional migration and increased expression of nerve regeneration factors. |
Expression analysis, Western blot for pYAP-Ser127, immunofluorescence for YAP localization, proliferation and migration assays (scratch assay) |
PloS one |
Medium |
23593160
|
| 2016 |
FRMD6 inhibits activation of receptor tyrosine kinases c-Met and PDGFR and their downstream ERK and AKT kinases in glioblastoma cells. Increased FRMD6 expression displays little effect on the Hippo pathway in GBM cells (negative result for Hippo activation). Expression of constitutively active c-Met (TPR-Met) largely reverses the anti-GBM effect of FRMD6 in vivo, placing FRMD6 upstream of RTK activity. |
Overexpression and knockdown in GBM cell lines, Western blot for RTK/ERK/AKT phosphorylation, xenograft rescue with TPR-Met constitutively active construct |
Oncotarget |
Medium |
27661120
|
| 2019 |
In aged cardiac microvascular endothelial cells, BDNF-TrkB-T1 signaling recruits Willin/FRMD6 as a downstream effector to activate the Hippo pathway, which promotes cell migration. Willin acts downstream of TrkB-T1 in the BDNF-TrkB-T1-Willin-Hippo pathway. |
Co-immunoprecipitation/protein interaction, knockdown, cell migration assay, pathway epistasis in aged CMECs |
Aging cell |
Medium |
30667167
|
| 2020 |
Willin/FRMD6 expression influences the mechanical phenotype and neuronal differentiation of SH-SY5Y neuronal cells by inversely regulating ERK1/2 pathway activity and downstream transcription factor NeuroD1. Changes in Willin/FRMD6 levels alter cell morphology, neurite-like extension formation, actin stress fiber organization, focal adhesion formation, and cell force. |
Overexpression and knockdown in SH-SY5Y cells, Elastic Resonator Interference Stress Microscopy (ERISM), Western blot for ERK1/2 phosphorylation and NeuroD1, immunofluorescence for actin/focal adhesions |
Frontiers in cellular neuroscience |
Medium |
33088261
|
| 2020 |
FRMD6 functions as a tumor suppressor in prostate cancer. CRISPR/Cas9 knockout of FRMD6 leads to enrichment of Hippo/YAP and c-MYC signaling (phospho-proteomic profiling). Frmd6/Pten double knockout in mouse prostate causes high-grade prostatic intraepithelial neoplasia and hyperproliferation, more severe than Pten single knockout alone, establishing FRMD6 as a cooperating suppressor with PTEN. |
CRISPR/Cas9 knockout, overexpression in PC cell lines, transcriptomic/proteomic/phospho-proteomic profiling, orthotopic mouse knockout model with histopathology |
Oncogene |
High |
33249427
|
| 2022 |
Willin/FRMD6 knockdown leads to mitochondrial dysfunction, mitochondrial fragmentation, and upregulation of ERK1/2 signaling in hippocampal HT-22 cells and primary neurons. Amyloid-beta (Aβ) induces downregulation of Willin/FRMD6 protein expression. Increasing Willin/FRMD6 expression rescues Aβ-induced abnormalities in mitochondrial morphology, function, and energetics. |
siRNA knockdown, overexpression, Aβ treatment, mitochondrial morphology imaging, mitochondrial function assays (energetics), Western blot for ERK1/2 in HT-22 and primary mouse neurons |
Cells |
Medium |
36231104
|
| 2023 |
FRMD6 interacts and co-localizes with mTOR and S6K in lung cancer cells, markedly enhances the interaction between mTOR and S6K, and increases phosphorylation of S6K and downstream S6. Knockout of FRMD6 in MEFs and mice inhibits mTOR signaling pathway activation, promoting lung cancer progression through mTOR pathway activation. |
Co-immunoprecipitation, co-localization (immunofluorescence), overexpression and knockout (FRMD6 KO MEFs and mice), Western blot for pS6K and pS6 |
Frontiers of medicine |
Medium |
37060526
|
| 2024 |
FRMD6 is upregulated in senescent fibroblasts, directly interacts with and activates MST kinase, leading to YAP/TAZ inactivation (increased inhibitory phosphorylation). FRMD6 overexpression alone is sufficient to induce senescence; FRMD6 silencing mitigates senescence. FRMD6 expression in senescent cells is regulated by p53 and SMAD transcription factors and induced by TGF-β. |
Proteomic analysis in senescent IMR90, FRMD6 overexpression and silencing, Co-IP for FRMD6-MST kinase interaction, Western blot for pYAP/pTAZ, TGF-β treatment, immunofluorescence in patient fibroblastic foci |
Cell death and differentiation |
High |
38926528
|
| 2026 |
FRMD6 was identified as the most significantly altered upstream regulator in Si3N4 nanoparticle-treated endothelial cells. FRMD6 knockdown restores adherens junction stability and abolishes Si3N4-mediated pro-angiogenic effects, including VE-cadherin phosphorylation and AJ dissociation. Local FRMD6 knockdown in vivo impairs Si3N4-promoted neovascularization and bone regeneration. |
Transcriptome sequencing, FRMD6 knockdown, Western blot for pVE-cadherin, angiogenesis assays, rat calvarial defect in vivo model |
Biomaterials |
Medium |
41916139
|
| 2026 |
L-Theanine (via TAS1R1 receptor) promotes FRMD6 expression, which enhances the interaction between FRMD6 and mTOR, promotes mTOR translocation from cytoplasm to the lysosomal surface, and activates mTORC1 signaling to promote milk synthesis in bovine mammary epithelial cells. |
TAS1R1 and FRMD6 knockdown and overexpression, transcriptome sequencing, Co-immunoprecipitation for FRMD6-mTOR interaction, subcellular fractionation/immunofluorescence for mTOR localization, Western blot for mTORC1 targets |
The Journal of nutritional biochemistry |
Medium |
42097464
|