| 2008 |
SEMA3F forms a complex with NRP2 (neuropilin-2) and plexin A1, triggering a signaling cascade in which ABL2/ARG tyrosine kinase directly binds plexin A1 (but not a plexin A1 mutant lacking the cytoplasmic domain), phosphorylates and activates p190RhoGAP, which inactivates RhoA (GTP to GDP), resulting in cytoskeletal collapse and inhibition of cell migration in glioma cells and endothelial cells. |
Co-immunoprecipitation, direct binding assay with plexin A1 cytoplasmic domain mutant, siRNA knockdown of ABL2 and p190RhoGAP, RhoA activity assays, cell migration assays |
The Journal of biological chemistry |
High |
18660502
|
| 2003 |
SEMA3F inhibits cell attachment and spreading in breast cancer cells through neuropilin receptors (NRP1 in MCF7 cells, NRP2 in C100 cells), with antagonistic effects to VEGF; SEMA3F treatment caused redistribution of Rac1-GFP to the base of collapsing lamellipodia, indicating modulation of Rac1 localization rather than total GTP-bound Rac1 or RhoA levels. |
Cell attachment/spreading assays, blocking anti-NRP1/NRP2 antibodies, time-lapse microscopy with Rac1-GFP, GTPase pull-down assays (negative for total GTP-Rac1/RhoA changes) |
Neoplasia (New York, N.Y.) |
Medium |
12659673
|
| 2005 |
SEMA3F has a repulsive effect on motile breast cancer cells (C100) mediated through NRP2, and inhibits E-cadherin-mediated cell contacts in MCF7 cells expressing NRP1; SEMA3F suppresses cell spreading and proliferation. |
3D gradient migration assay, stripe assay, blocking anti-NRP1/NRP2 antibodies, loss of membrane-associated E-cadherin and beta-catenin assessed by imaging |
Neoplasia (New York, N.Y.) |
Medium |
15802023
|
| 2007 |
SEMA3F expression in lung cancer H157 cells decreases integrin-linked kinase (ILK) kinase activity, reduces activated αVβ3 integrin and adhesion to extracellular matrix, and down-regulates phospho-ERK1/2, phospho-AKT, and phospho-STAT3 signaling; downstream consequences include reduced HIF-1α protein (via inhibition of AKT-driven translation initiation, with no effect on HIF-1α mRNA or protein degradation) and reduced VEGF mRNA. |
Stable SEMA3F transfection (constitutive and inducible), ILK kinase activity assay, siRNA knockdown of ILK, phospho-protein analysis, conditioned medium experiments, nude mouse xenograft with microvessel density quantification |
Cancer research |
High |
17875711
|
| 2005 |
SEMA3F selectively suppresses in vivo tumorigenicity in NCI-H157 lung cancer cells (which express NRP2) but not in NCI-H460 cells (which express NRP1 but not NRP2), establishing NRP2 as the functionally required receptor for SEMA3F antitumor activity; this is associated with loss of activated αVβ3 integrin and loss of p42/p44 MAPK phosphorylation. |
Orthotopic rat lung cancer model, retroviral stable transfection, receptor expression analysis, integrin activation assay, MAPK phosphorylation assay |
Neoplasia (New York, N.Y.) |
High |
15967098
|
| 2015 |
SEMA3F acts predominantly through NRP2 to collapse lymphatic endothelial cells (LECs) and potently inhibit lymphangiogenesis in vivo; reconstitution of all plexin and neuropilin receptor combinations identified NRP2 as the principal signaling co-receptor in LECs; SEMA3F re-expression in HNSCC orthotopic mouse models diminishes lymphangiogenesis and lymph node metastasis. |
Recombinant SEMA3F protein treatment, reconstitution of plexin/neuropilin receptor combinations in LECs, in vivo lymphangiogenesis assays, orthotopic HNSCC mouse metastasis models |
Cancer research |
High |
25952650
|
| 2017 |
Sema3F-Neuropilin-2/PlexinA3 signaling mediates homeostatic synaptic downscaling in cortical neurons in response to increased neuronal activity; NRP2 physically associates with AMPA-type glutamate receptor (AMPAR) subunit GluA1, and Sema3F regulates this interaction to control cell surface AMPAR levels. |
Co-immunoprecipitation of NRP2 with GluA1, genetic loss-of-function (Npn-2 and PlexA3 knockout mice), electrophysiology for homeostatic scaling, surface AMPAR quantification |
Neuron |
High |
29154130
|
| 2020 |
CRMP2 mediates Sema3F-dependent axon pruning in hippocampus and visual cortex and dendritic spine remodeling; crmp2-/- mice display defects consistent with impaired Sema3F (not Sema3A) signaling, and CRMP2 was shown to mediate Sema3F signaling in primary neurons. |
crmp2 knockout mice, in vitro primary neuron Sema3F signaling assay, histological analysis of axon pruning and spine remodeling, behavioral assays |
EMBO reports |
High |
31919978
|
| 2012 |
RORα directly regulates transcription of SEMA3F, as established by chromatin immunoprecipitation and luciferase reporter assays; knockdown of SEMA3F in RORα-expressing cancer cells rescued aggressive 3D phenotypes and tumor invasion, placing SEMA3F downstream of RORα as the effector of its tumor-suppressive activity. |
Chromatin immunoprecipitation (ChIP), luciferase reporter assay, siRNA knockdown of SEMA3F, 3D culture invasion assay, nude mouse tumor growth |
Cancer research |
High |
22350413
|
| 2015 |
SEMA3F inhibits invasion and metastasis of colorectal cancer cells through PI3K-AKT-dependent down-regulation of the ASCL2-CXCR4 axis; the CXCR4 antagonist AMD3100 attenuated SEMA3F knockdown-induced invasion in vitro and in vivo, placing CXCR4 downstream of SEMA3F/PI3K-AKT/ASCL2. |
SEMA3F knockdown and overexpression in CRC cells, PI3K-AKT pathway inhibitors, CXCR4 antagonist (AMD3100) rescue experiments, in vitro invasion assay, in vivo metastasis model |
The Journal of pathology |
Medium |
25866254
|
| 2017 |
In the extraembryonic yolk sac, Sema3F signals to inhibit the phosphorylation-dependent degradation of Myc, which drives expression of the proangiogenic microRNA cluster 17/92 and suppresses Thrombospondin-1 (Thbs1); in Sema3f-null yolk sacs, miR-17/92 transcription is impaired, Thbs1 synthesis is increased, and Vegf signaling is inhibited in yolk sac endothelial cells — establishing a proangiogenic (rather than antiangiogenic) role for Sema3F in extraembryonic tissue. |
Sema3f knockout mice, exogenous recombinant Sema3F treatment of differentiated F9 cells, Myc phosphorylation assays, miRNA expression analysis, Thbs1 protein quantification, in vivo vascular phenotyping |
Arteriosclerosis, thrombosis, and vascular biology |
High |
28729362
|
| 2007 |
SEMA3F directly binds to the cytoplasmic loop domain of connexin 43 (Cx43), as demonstrated by yeast two-hybrid assay; SEMA3F siRNA knockdown in IAR20 cells reduced Cx43 localization in the plasma membrane and gap junctional intercellular communication (GJIC), establishing SEMA3F as a regulator of Cx43 membrane localization and function. |
Yeast two-hybrid complementation and screening, immunolocalization, siRNA knockdown, GJIC functional assay |
The Journal of membrane biology |
Medium |
17665084
|
| 2010 |
Sema3F is secreted by early-arriving olfactory sensory neuron (OSN) axons and deposited at the anterodorsal olfactory bulb, where it repels Nrp2-positive axons arriving later; complementary graded expression of Nrp2 and Sema3F by OSNs and sequential axon arrival together establish topographic order along the dorsal-ventral axis of the olfactory bulb. |
Mouse genetic models with complementary Nrp2/Sema3F expression analysis, axon tracing, olfactory bulb topography mapping |
Cell |
High |
20550939
|
| 2003 |
Ectopic Sema3F expression in COS1 cell clusters placed on embryonic neocortical slices reduced migration of Nrp2-positive GABAergic neurons from the ganglionic eminence; combining Sema3A and Sema3F expression almost completely blocked migration, and ectopic Sema3F in vivo diverted Dlx2-positive cells to the upper intermediate zone — establishing Sema3F/Nrp2 as a regulator of cortical GABAergic interneuron migration. |
Slice culture assay with COS1 cell clusters expressing Sema3F, in vivo ectopic Sema3F expression, Dlx2 immunolabeling, neuropilin expression analysis |
The Journal of comparative neurology |
Medium |
12454988
|
| 2005 |
SEMA3F promoter methylation at position −3850 to −3644 nt significantly correlates with loss of SEMA3F expression in lung cancer cell lines; however, histone deacetylase inhibition (Trichostatin A) was more effective than demethylation (5-aza-2'-deoxycytidine) in reactivating SEMA3F, indicating chromatin remodeling via HDAC inhibition is sufficient to activate SEMA3F transcription. |
Southern blot, methylation-specific PCR, Trichostatin A and 5-aza-2'-deoxycytidine treatment, transcriptional initiation site mapping |
Biochimica et biophysica acta |
Medium |
16005989
|
| 2021 |
Loss-of-function variants in SEMA3F and its receptor PLXNA3 cause idiopathic hypogonadotropic hypogonadism (IHH); SEMA3F and PLXNA3 are expressed along the olfactory nerve and vomeronasal/terminal nerve during early human fetal development, and PLXNA1-A3 are expressed in early migratory GnRH neurons, establishing SEMA3F/PLXNA signaling as required for GnRH neuron guidance in humans. |
Exome sequencing of 216 IHH patients, functional assays in HEK293T cells with WT vs. variant plasmids, fluorescent IHC in human fetal nasal region and nasal/forebrain junction |
Genetics in medicine |
Medium |
33495532
|
| 2025 |
Missense variants in SEMA3F associated with human nonsyndromic hearing loss decreased furin-mediated processing of SEMA3F and abolished SEMA3F-induced collapse of filamentous actin cytoskeleton in endothelial cells; inner ear-specific Sema3f knockout mice exhibited hearing loss with abnormal spiral ganglion neuron projections into outer hair cell regions. |
Inner ear-specific Sema3f knockout mice, auditory brainstem response and DPOAE testing, spiral ganglion neuron tracing, in vitro furin cleavage assay, F-actin collapse assay in HUVECs with patient variants |
Molecules and cells |
High |
39909336
|
| 2012 |
Sema3F down-regulates p53 expression in primary hippocampal neurons, contributing to growth cone collapse; p53 overexpression partially rescued Sema3F-induced growth cone collapse, while p53 inhibition or siRNA knockdown alone caused collapse, establishing p53 as a required downstream mediator of growth cone structure. |
Primary hippocampal neuron culture, Sema3F treatment, p53 siRNA and inhibitor, p53 overexpression rescue, growth cone morphology quantification |
International journal of clinical and experimental pathology |
Low |
22977659
|
| 2025 |
A bispecific antibody dimerizing NRP2 and PLXNA1 mimics SEMA3F-mediated NRP2-dependent signaling (receptor dimerization, phospho-AKT reduction, oncogene expression suppression, cell proliferation inhibition); structural studies showed the antibody binds PLXNA1/NRP2 at sites distinct from the SEMA3F-binding site but allows proper spacing for receptor complex formation and signaling. |
Cell-based receptor dimerization assay, phospho-AKT assay, cell proliferation assay, structural studies of antibody-receptor binding |
The Journal of biological chemistry |
Medium |
41391772
|
| 2025 |
In TIE2-mutant endothelial cells (venous malformation model), Sema3F (and Sema3A) are overexpressed and act as chemorepellents to inhibit wild-type endothelial cell sprouting and lumen formation; shRNA-mediated silencing of Sema3F (or Sema3A) in TIE2-mutant EC rescued the chemorepellent phenotype, restored wild-type EC migration and sprouting, and normalized vessel size in vivo. |
Xenograft murine VM model, 3D fibrin gel lumen formation assay, cell migration confrontation assay, RNA-sequencing, shRNA knockdown of Sema3F/Sema3A, in vivo vessel morphology analysis |
bioRxivpreprint |
Medium |
|