| 2022 |
Flot2 acts as a scaffolding protein that promotes cytoneme-based intercellular transport of Wnt3 in gastric cancer cells. Together with the Wnt co-receptor Ror2, Flot2 determines the number and length of Wnt3-carrying cytonemes. This mechanism is conserved: Flotillins are also necessary for Wnt8a cytonemes during zebrafish embryogenesis. |
Live imaging of cytonemes, genetic manipulation of Flot2 and Ror2, zebrafish embryogenesis model, functional proliferation/survival assays |
eLife |
High |
36040316
|
| 2021 |
FLOT2 interacts with and stabilizes EphA2 protein in glioma cells; FLOT2 knockdown reduces EphA2 levels, suppresses Akt and NF-κB activities, and induces apoptosis, cell cycle arrest, and EMT inhibition. Restoration of EphA2 rescues the suppressive effects of FLOT2 knockdown, placing FLOT2 upstream of EphA2 in a pro-oncogenic signaling axis. |
Co-immunoprecipitation, siRNA knockdown, Western blot, IHC, functional rescue assays |
Biochemical and biophysical research communications |
Medium |
33631676
|
| 2025 |
LAMP2 preferentially binds FLOT2 in cardiac endothelial cells following IL-4 exposure, and this LAMP2-FLOT2 interaction enhances autophagosome-lysosome fusion. Loss of FLOT2 reverses the LAMP2-mediated rescue of autophagic flux, leading to autophagosome accumulation. |
Co-immunoprecipitation, loss-of-function (FLOT2 knockdown), autophagic flux assays (including transmission electron microscopy and LC3/p62 markers), CLP mouse sepsis model |
Autophagy |
Medium |
40066518
|
| 2025 |
Flot2 directly interacts with synaptopodin in podocytes and protects it from proteasomal degradation via inhibition of K48-linked polyubiquitination. Podocyte-specific Flot2 knockout worsened albuminuria and podocyte injury in diabetic mice, while podocyte-specific overexpression was protective. |
Co-immunoprecipitation, conditional knockout and overexpression mouse models, ubiquitination assays, Western blot |
Metabolism: clinical and experimental |
High |
40681143
|
| 2023 |
Flot2 stabilizes the podocin-nephrin complex by recruiting podocin and nephrin into lipid rafts. Flot2 and podocin directly interact via their SPFH domains. Podocyte-specific Flot2 deletion worsened albuminuria and glomerular pathology in LPS/ADR-induced nephropathy, while podocyte-specific overexpression was protective. Flot2 was identified as a direct transcriptional target of KLF15. |
Co-immunoprecipitation, domain mapping (SPFH), conditional knockout and transgenic overexpression mouse models, sucrose density fractionation, ChIP/luciferase for KLF15 regulation |
International journal of biological sciences |
High |
36632460
|
| 2024 |
HDAC6 deacetylates FLOT2 at lysine 211 (K211), inhibiting its proteasomal degradation. Acetylation-mimicking mutation (K211R) slows FLOT2 degradation and increases its tumorigenic activity. HDAC6 and FLOT2 interact (confirmed by Co-IP), and HDAC6 knockdown increases FLOT2 acetylation and reduces FLOT2 protein levels via the proteasome. |
Co-immunoprecipitation, site-directed mutagenesis (K211R), cycloheximide chase assay, proteasome inhibitor (MG132) treatment, HDAC inhibitor (TSA) treatment, Western blot |
Journal of Central South University. Medical sciences |
High |
39174882
|
| 2024 |
HNRNPH1 stabilizes FLOT2 mRNA through an m6A-dependent mechanism: HNRNPH1 interacts with and protects METTL14 from STUB1-mediated degradation, leading to increased m6A modification of FLOT2 mRNA, which is then recognized by IGF2BP3 to further stabilize it. Restoration of METTL14 in HNRNPH1-depleted cells rescues FLOT2 expression and malignant phenotype, but not when FLOT2 is also knocked down. |
Co-immunoprecipitation, mRNA stability assays, m6A methylation analysis, rescue experiments with METTL14 and FLOT2, in vitro and in vivo functional assays |
Cellular oncology |
Medium |
39570559
|
| 2024 |
FTO demethylates m6A modifications in FLOT2 mRNA, stabilizing it and upregulating FLOT2 protein expression, which subsequently activates the PI3K/Akt/mTOR signaling pathway in DLBCL. FTO overexpression promotes and FTO silencing suppresses DLBCL malignant phenotypes through FLOT2. |
m6A methylation assays, mRNA stability assays, overexpression/silencing vectors, Western blot, functional assays (viability, apoptosis, invasion), rescue experiments with FLOT2 |
Archives of biochemistry and biophysics |
Medium |
38914215
|
| 2017 |
Flot2 promotes HCC tumor growth and metastasis by activating the Raf/MEK/ERK1/2 pathway, upregulating Twist, which drives cell cycle modulation and EMT induction. Forced overexpression of Flot2 promoted proliferation, migration, and invasion, while silencing inhibited these processes both in vitro and in vivo. |
Overexpression and siRNA knockdown, Western blot, in vitro functional assays, in vivo xenograft model, pathway analysis |
American journal of cancer research |
Medium |
28560058
|
| 2019 |
During neural differentiation of P19C6 cells, Flot2 expression and localization to lipid rafts increases. Fyn kinase co-localizes with Flot2 in lipid rafts and partially colocalizes after neural differentiation, suggesting Fyn phosphorylates Flot2 in lipid rafts during neural differentiation. |
Sucrose density gradient fractionation, immunofluorescence co-localization, Western blot of detergent-resistant membrane fractions |
BMC molecular and cell biology |
Medium |
31455216
|
| 2017 |
LXR agonist T0901317 decreases mRNA and protein expression of FLOT2 and its palmitoylating enzyme DHHC5 in MCF-7 breast cancer cells, and reduces Akt phosphorylation and its localization at the plasma membrane, indicating LXR-mediated transcriptional regulation of FLOT2 affects lipid raft integrity and downstream Akt signaling. |
LXR agonist treatment, RT-PCR, Western blot, Akt localization assay |
Anticancer research |
Low |
28739689
|
| 2022 |
FLOT2 promotes NPC progression by stabilizing STAT3 protein, which then transcriptionally activates CD109 expression. CD109 upregulation suppresses the TGF-β/Smad pathway. Rescue experiments showed CD109 reverses functional changes induced by FLOT2 alteration in vitro and in vivo. |
Co-immunoprecipitation, immunofluorescence, ChIP, dual-luciferase assay, qRT-PCR, Western blot, in vitro and in vivo functional assays |
iScience |
Medium |
38161417
|
| 2022 |
TBL1X interacts with TCF4 to trans-activate Flot2 expression. Flot2 in turn increases TBL1X expression by upregulating c-myc, a positive transcriptional regulator of TBL1X, forming a positive feedback loop that promotes NPC metastasis. |
Co-immunoprecipitation, luciferase reporter assay, qRT-PCR, Western blot, in vitro and in vivo functional assays |
International journal of biological sciences |
Medium |
35173544
|
| 2023 |
Flot2 deficiency in B cells leads to elevated effector B cell (Beff) cytokines (IL-6, IL-1β, CXCL10) without affecting regulatory B cell (Breg) cytokines (IL-10, TGF-β), exacerbating sepsis-induced lung injury and reducing survival. Flot2 acts as a suppressor of Beff inflammatory responses. |
B cell-specific Flot2 knockout mice and chimeric mice, RNA-seq, ELISA, in vivo CLP sepsis model |
Immunology |
Medium |
37688314
|
| 2025 |
FLOT2 interacts with PLCγ2 in osteoclast precursor cells; FLOT2 deficiency disrupts this interaction and inhibits osteoclastogenesis. Targeted ablation of Flot2 using CRISPR/Cas9 and siRNA suppressed osteoclastogenesis in vitro and prevented ovariectomy-induced osteoporosis in vivo without affecting physiological bone mass. |
CRISPR/Cas9 knockout, siRNA knockdown, Co-immunoprecipitation (FLOT2-PLCγ2), in vitro osteoclastogenesis assays, in vivo OVX mouse model |
Pharmacological research |
High |
40816424
|
| 2015 |
miR-449a directly targets the 3'UTR of Flot2 (validated by luciferase reporter assay), reducing Flot2 expression. Flot2 is necessary for TGF-β-induced EMT in gastric cancer cells; its silencing reduces mesenchymal markers and increases E-cadherin, suppressing invasion. |
Luciferase reporter assay, qRT-PCR, Western blot, invasion assays |
Diagnostic pathology |
Medium |
26576674
|
| 2023 |
Loss of Flot2 expression in deep cerebellar nuclei neurons of Npc1 knockout mice correlates with lipid raft disruption due to GM2 ganglioside sequestration. Treatment with miglustat (sphingolipid synthesis inhibitor) or N-acetyl-l-leucine restored Flot2 expression in Npc1-deficient mice. |
Npc1 knockout mouse model, immunostaining, single-nucleus RNA sequencing, pharmacological treatment |
Heliyon |
Low |
37539272
|