| 2003 |
FERMT2 (Mig-2) localizes to cell-matrix adhesions, interacts with migfilin through Mig-2's C-terminal domain, and with filamin through migfilin's N-terminal domain. Mig-2 recruits migfilin to cell-matrix adhesions, and migfilin's interaction with filamin mediates its association with actin filaments. Loss of Mig-2 impairs cell shape modulation. |
Co-immunoprecipitation, pulldown assays, dominant-negative/loss-of-function cell experiments, localization by immunofluorescence |
Cell |
High |
12679033
|
| 2007 |
FERMT2 (Mig-2) binds directly to beta1 and beta3 integrin cytoplasmic domains via a single site within its FERM domain. This interaction recruits Mig-2 to focal adhesions, promotes integrin activation, and enhances cell-ECM adhesion. An integrin-binding-defective Mig-2 mutant fails to strengthen cell-matrix adhesion or reduce cell motility. |
Co-immunoprecipitation, site-directed mutagenesis of the FERM domain, integrin activation assays in CHO cells, cell adhesion and motility assays |
The Journal of biological chemistry |
High |
17513299
|
| 2008 |
FERMT2 (Kindlin-2) binds to the C-terminal region of integrin beta3 cytoplasmic tail (TS752T region and NITY759 motif) and functions as a co-activator of beta3 integrins. Co-transfection with talin head domain produces synergistic enhancement of alphaIIbbeta3 activation. siRNA knockdown of endogenous kindlin-2 impairs talin-induced alphaIIbbeta3 activation and blunts alphaVbeta3-mediated adhesion and migration. |
Co-immunoprecipitation, integrin activation assays (flow cytometry for PAC-1 binding), siRNA knockdown, cell adhesion/migration assays |
The Journal of cell biology |
High |
18458155
|
| 2016 |
FERMT2 underexpression increases Abeta peptide production by raising levels of mature APP at the cell surface and facilitating its recycling, as shown by genome-wide high-content siRNA screening and follow-up mechanistic assays. |
Genome-wide high-content siRNA screening, APP metabolism assays, cell surface APP quantification, APP recycling assays |
Acta neuropathologica |
Medium |
27933404
|
| 2018 |
In podocytes, loss of FERMT2 results in altered cortical actin composition, cell cortex destabilization with plasma membrane blebbing, remodeling of focal adhesions, and elevated RhoA activation with increased actomyosin contractility. Inhibition of actomyosin tension reverses the membrane blebbing phenotype, linking FERMT2 to the regulation of plasma membrane tension via cell-matrix adhesion. |
Conditional FERMT2 knockout (in vivo and CRISPR/Cas9-modified human podocytes), RhoA activity assay, actomyosin inhibitor rescue experiments, actin fractionation, focal adhesion analysis |
Matrix biology : journal of the International Society for Matrix Biology |
High |
29337051
|
| 2019 |
siRNA-mediated knockdown of FERMT2 in human iPSC-derived neurons reduces extracellular Abeta levels and reduces the proportion of phosphorylated TAU. CRISPR-Cas9 targeting of FERMT2 in familial AD human neurons validated reduced extracellular Abeta. In familial AD neurons, FERMT2 reduction elevated Abeta42:40 ratio with no reduction in phospho-TAU, revealing cell-context-dependent effects. |
shRNA knockdown, CRISPR-Cas9 knockout in iPSC-derived neurons, ELISA for extracellular Abeta, phospho-TAU immunoassay |
Human molecular genetics |
Medium |
30371777
|
| 2018 |
FERMT2 is prominently localized to extravillous trophoblast cell periphery. siRNA knockdown of FERMT2 in HTR8-SVneo trophoblast cells significantly decreases cell-substrate attachment and invasion, demonstrating a role in integrin-mediated trophoblast invasion. |
siRNA knockdown, cell-substrate adhesion assays, Matrigel invasion assays, immunofluorescence localization |
BMC developmental biology |
Medium |
30382829
|
| 2020 |
FERMT2 directly interacts with APP to modulate its metabolism. FERMT2 underexpression impairs axonal growth, synaptic connectivity, and long-term potentiation in an APP-dependent manner. The rs7143400-T AD-risk allele in the FERMT2 3'UTR reduces FERMT2 expression through miR-4504 binding. |
Co-immunoprecipitation for FERMT2-APP interaction, genome-wide high-content screening, neuronal loss-of-function experiments (axon growth assay, LTP assay), luciferase reporter assay for miRNA binding |
Molecular psychiatry |
Medium |
33144711
|
| 2014 |
Mig-2 (FERMT2) attenuates cisplatin-induced apoptosis in glioma cells via AKT/JNK and AKT/p38 signaling pathways. The F3 subdomain of Mig-2 is necessary and sufficient for this anti-apoptotic effect; a mutant lacking F3 is inactive. Overexpression reduces cleaved caspases and p-JNK/p-p38 while increasing p-AKT. |
Plasmid overexpression, siRNA knockdown, domain deletion mutants (F3 subdomain), Western blotting, pharmacological inhibitors (SP600125, SB203580, LY294002), flow cytometry apoptosis assay |
Acta pharmacologica Sinica |
Medium |
25152024
|
| 2025 |
KINDLIN2 (FERMT2) is a substrate of caspases and calpain I. These proteolytic cleavages dissociate the F0 and F1 domains of KINDLIN2 and decrease its ability to control APP processing, representing a potential mechanism regulating synaptic function relevant to AD pathophysiology. |
In vitro caspase/calpain cleavage assays, domain dissociation analysis, APP processing assays following KINDLIN2 cleavage |
Neurobiology of aging |
Medium |
40273529
|
| 2025 |
FERMT2 promotes anoikis resistance in gastric cancer by suppressing ubiquitination of SOX2, thereby enhancing its stability and upregulating FN1 transcription and extracellular fibronectin matrix deposition. TGFbeta-RI forms a positive feedback loop with FERMT2 via TGFbeta-1/TGFbeta-RI signaling to drive this process. |
In vitro and in vivo functional assays, ubiquitination assay for SOX2, transcription assay for FN1, co-expression and knockdown experiments, peritoneal metastasis mouse model |
Gastric cancer |
Medium |
40024947
|
| 2026 |
FERMT2 is required for YAP/TAZ nuclear accumulation and transcriptional activity in breast cancer cells. FERMT2 regulates YAP/TAZ independently of the canonical Hippo pathway through integrin-mediated activation of FAK; glucocorticoid-driven FAK activation restores YAP/TAZ signaling in FERMT2-depleted cells. FERMT2 also modulates actin-dependent regulation of YAP/TAZ. |
CRISPR/Cas9 loss-of-function screens (in vitro and in vivo), FERMT2 knockout and silencing, YAP/TAZ nuclear localization assays, YAP/TAZ target gene expression, FAK phosphorylation assays, pharmacological FAK activation rescue, epistasis analysis |
Cell death and differentiation |
Medium |
41792242
|
| 2025 |
In gastric cancer-associated fibroblasts, FERMT2 maintains the myofibroblastic phenotype by acting as a competing endogenous RNA (ceRNA) for ZEB2, thereby promoting alpha-SMA transcription. FERMT2 drives GCAF secretion of TGF-beta1, which in turn induces FERMT2 in tumor cells. Tumor-derived FERMT2 upregulates COL6A1 and facilitates its transfer to GCAFs via exosomes, reinforcing a TGF-beta1/FERMT2/COL6A1 positive feedback loop. |
Bulk and single-cell transcriptomics, functional assays, proteomics, in vivo peritoneal metastasis model, ceRNA analysis, exosome isolation and transfer experiments |
International journal of biological sciences |
Low |
41079932
|