| 2002 |
FOXC1 transcriptional regulation is mediated by two activation domains (extreme N- and C-terminal regions) and a central phosphorylated transcriptional inhibitory domain (residues 215-366). Two regions in the forkhead domain are necessary for nuclear localization, with only the basic amino-acid-rich region being sufficient. FOXC1 is a phosphoprotein and phosphorylation of residues in the inhibitory domain reduces transactivation; removal of the inhibitory domain produces a hyperactive, hypophosphorylated protein. |
Deletion mutagenesis, reporter-gene transactivation assays, nuclear-localization assays, phosphorylation analysis in cell-based experiments |
The Journal of biological chemistry |
High |
11782474
|
| 2006 |
FOXC1 and PITX2A physically interact; this interaction requires the C-terminal activation domain of FOXC1 and the homeodomain of PITX2A. PITX2A and FOXC1 colocalize within a common nuclear subcompartment. PITX2A negatively regulates FOXC1 transactivity, placing both proteins in a common developmental pathway for anterior segment morphogenesis. |
Co-immunoprecipitation, immunofluorescence colocalization, reporter-gene transactivation assays, domain-deletion analysis |
Human molecular genetics |
High |
16449236
|
| 2007 |
FOXC1 directly regulates FOXO1A transcription by binding to a conserved element in the FOXO1A promoter in vivo. Reduced FOXC1 expression decreases FOXO1A expression in human trabecular meshwork cells and zebrafish eyes, and increases cell death in response to oxidative stress, establishing FOXC1 as a mediator of cellular homeostasis through FOXO1A. |
Inducible FOXC1 expression with protein synthesis blockade (to identify direct targets), ChIP at the FOXO1A promoter, siRNA and morpholino knockdown, cell viability/death assays under oxidative stress |
Human molecular genetics |
High |
17993506
|
| 2006 |
FGF19 is a direct transcriptional target of FOXC1 in the eye. FOXC1 positively regulates FGF19 expression in corneal and periocular mesenchymal cells; FGF19 then signals through FGFR4 to promote MAPK phosphorylation in the developing and mature cornea. |
Chromatin enrichment (nickel-agarose), cell-culture overexpression/knockdown, zebrafish embryo experiments, MAPK phosphorylation assays |
Human molecular genetics |
High |
17000708
|
| 2008 |
Human p32 protein interacts with FOXC1 via the forkhead domain; p32 inhibits FOXC1-mediated transcriptional activation in a dose-dependent manner without affecting FOXC1 DNA-binding. The disease-causing F112S FOXC1 mutation impairs interaction with p32, suggesting disrupted protein-protein interaction as a disease mechanism. |
Yeast two-hybrid screen, Ni2+ pull-down, co-immunoprecipitation, immunofluorescence colocalization, EMSA, dual-luciferase reporter assays in human trabecular meshwork cells |
Investigative ophthalmology & visual science |
High |
18676636
|
| 2003 |
The L86F missense mutation in helix 1 of the FOXC1 forkhead domain does not affect nuclear localization but reduces DNA binding and significantly reduces transcriptional transactivation. The analogous L86P mutation more severely disrupts function, establishing the importance of helix 1 for FOXC1 structure and activity. |
Site-directed mutagenesis, nuclear localization assays, DNA-binding assays, transactivation reporter assays |
Investigative ophthalmology & visual science |
Medium |
14578375
|
| 2015 |
FOXC1 activates Smoothened-independent Hedgehog signaling in basal-like breast cancer by direct physical interaction between the N-terminal domain of FOXC1 (aa 1-68) and an internal region (aa 898-1168) of Gli2. This interaction enhances Gli2's DNA-binding and transcription-activating capacity, promoting cancer stem cell properties. |
Domain-mapping pulldown assays, reporter assays, ChIP, FOXC1 knockdown/overexpression with Gli2 rescue, xenograft models |
Cell reports |
High |
26565916
|
| 2017 |
FOXC1 directly binds the WNT5A promoter to activate its expression. WNT5A then activates NF-κB signaling to induce MMP7 expression, constituting a non-canonical WNT5A-NF-κB-MMP7 pathway essential for FOXC1-driven invasiveness in triple-negative breast cancer. enChIP-MS identified heterogeneous nuclear ribonucleoproteins as FOXC1-interacting proteins involved in WNT5A transcription. |
Pathway PCR array, ChIP (direct binding to WNT5A promoter), enChIP coupled with mass spectrometry, WNT5A and MMP7 KO/OE rescue experiments, xenograft lung metastasis models |
Oncogene |
High |
29249801
|
| 2011 |
BRCA1 and GATA3 form a transcriptional co-repressor complex on the FOXC1 distal promoter to repress FOXC1 expression; BRCA1 requires GATA3 for recruitment to this region. A mutant BRCA1 protein cannot localize to the FOXC1 promoter or repress FOXC1 expression. This repression is not FOXC1-specific, as FOXC2, CXCL1, and p-cadherin are co-repressed similarly. |
Co-immunoprecipitation of BRCA1-GATA3, ChIP at the FOXC1 promoter, reporter assays, mutant BRCA1 functional analysis |
Oncogene |
High |
22120723
|
| 2015 |
FOXC1 interacts physically and functionally with Gli2 to stimulate expression of Ihh target genes (PTHrP and Col10a1) during endochondral ossification. An Axenfeld-Rieger syndrome-associated missense mutation in FOXC1 impairs the Gli2-FOXC1 association and Ihh function. Loss of Foxc1 function in Foxc1(ch/ch) mice delays endochondral ossification and reduces Ihh target gene expression. |
In vivo microarray, co-immunoprecipitation of FOXC1-Gli2, dominant-negative FOXC1 overexpression, Foxc1 hypomorphic mouse model, ARS missense mutation functional analysis |
Nature communications |
High |
25808752
|
| 2014 |
Foxc1 is preferentially expressed in CAR (CXCL12-abundant reticular) mesenchymal progenitor cells in bone marrow. Conditional deletion of Foxc1 in mesenchymal or CAR cells depletes haematopoietic stem/progenitor cells, reduces CXCL12 and stem cell factor expression in CAR cells, and causes adipocytic conversion of marrow, establishing Foxc1 as a transcriptional regulator of the haematopoietic stem cell niche. |
Conditional and inducible Cre-mediated Foxc1 knockout in mice, flow cytometry of HSPCs, qPCR/in situ hybridization for CXCL12/SCF, histological analysis |
Nature |
High |
24590069
|
| 2016 |
Foxc1 reinforces quiescence in self-renewing hair follicle stem cells by transcriptionally activating Nfatc1 and BMP signaling, two key quiescence-governing mechanisms. Deletion of Foxc1 in activated (but not quiescent) stem cells causes failure to re-establish quiescence. |
Conditional Foxc1 deletion (Cre-lox) in hair follicle SCs, lineage tracing, gene expression analysis (Nfatc1, BMP targets), in vivo hair cycle phenotyping |
Science (New York, N.Y.) |
High |
26912704
|
| 2014 |
SDF1α is a direct transcriptional target of Foxc1 expressed in head mesenchyme. Loss of Foxc1 reduces SDF1α levels, impairing cerebellar radial glial proliferation and Purkinje cell migration; SDF1α rescues the Foxc1-/- cerebellar phenotype. Conditional deletion of SDF1α receptor Cxcr4 in neural progenitors (Nes-Cre) mimics the Foxc1-/- cerebellar phenotype. |
Foxc1-/- mouse cerebellar phenotyping, in vitro radial glial mitogen and chemoattractant assays with SDF1α, conditional Cxcr4 knockout, SDF1α rescue experiment |
eLife |
High |
25513817
|
| 2016 |
FOXC1 and FOXC2 are essential regulators of lymphangiogenesis via control of ERK signaling in lymphatic endothelial cells. LEC-specific deletion of Foxc1 and/or Foxc2 causes aberrant Ras regulator expression and ERK hyperactivation; pharmacological ERK inhibition in utero rescues the abnormal lymphatic phenotype. |
LEC-specific conditional Foxc1/Foxc2 knockout mice, ERK phosphorylation analysis, gene expression profiling, in utero ERK inhibitor treatment rescue |
The Journal of clinical investigation |
High |
27214551
|
| 2014 |
foxc1b-expressing mesenchymal cells differentiate into acta2-expressing vascular smooth muscle cells in zebrafish head. foxc1 is expressed upstream of acta2 and is required for acta2 expression; loss of foxc1 function blocks vSMC differentiation without affecting pericytes. |
Timelapse live imaging, CRISPR/morpholino loss-of-function, RNA-seq gene expression profiling, marker co-expression analysis |
Developmental biology |
High |
31199900
|
| 2020 |
FOXC1 and FOXC2 are induced by laminar (not oscillatory) shear stress in lymphatic endothelial cells. FOXC1 KD increases focal adhesions and actin stress fibers whereas FOXC2 KD disrupts cell junctions, both mediated by increased ROCK activation. ROCK inhibition rescues FOXC1-dependent cytoskeletal changes in vitro and FOXC2-dependent valve degeneration in vivo. |
Shear stress cell culture experiments, inducible endothelial-specific Foxc1/Foxc2 deletion in mice, siRNA knockdown, ROCK inhibitor rescue, cytoskeletal/junctional marker analysis |
eLife |
High |
32510325
|
| 2013 |
Foxc1 and Fgf8 genetically interact in jaw patterning; reduction of Fgf8 dosage modifies the syngnathic phenotype of Foxc1 null mice. Loss of Foxc1 causes ectopic osteoblast development in the maxillary prominence leading to bony fusion (syngnathia), establishing Foxc1 as a regulator of neural crest-derived osteogenic patterning in jaw development. |
Foxc1 null mouse phenotyping, Fgf8 compound genetic interaction, histology, in situ hybridization for osteogenic markers |
PLoS genetics |
Medium |
24385915
|
| 2005 |
FGF2 regulates Foxc1 expression in calvarial mesenchyme, and Foxc1 integrates BMP and FGF signaling pathways (required for BMP regulation of Msx2) independently of Twist or Noggin during calvarial bone development. |
Foxc1 null mouse analysis, FGF2 treatment of calvarial cells, expression analysis of Fgf receptors/Twist/Noggin/Msx2, osteogenic differentiation assays |
Developmental dynamics |
Medium |
15906377
|
| 2004 |
Foxc1 and Foxc2 regulate paraxial versus intermediate mesoderm cell fate specification. Mouse embryos lacking both genes show expansion of intermediate mesoderm markers into the paraxial domain and ectopic mesonephric tubules. Gain-of-function of Foxc1/Foxc2 in chick prospective intermediate mesoderm drives paraxial fate (Pax7, Paraxis expression). |
Foxc1/Foxc2 double knockout mouse embryo analysis, chick in ovo gain-of-function electroporation, in situ hybridization for mesoderm markers |
Developmental biology |
High |
15196959
|
| 2002 |
FOXC1 is a TGF-β1-responsive gene; TGF-β1 upregulates FOXC1 transcription. Ectopic FOXC1 expression in HeLa cells (which lack FOXC1) restores TGF-β1-mediated G0/G1 cell cycle arrest, placing FOXC1 as a downstream mediator of TGF-β1 growth-inhibitory signaling. |
Gene cloning from TGF-β1-treated cells, FOXC1 cDNA transfection rescue assay in HeLa cells, cell cycle analysis (G0/G1 arrest readout) |
Genomics |
Medium |
12408963
|
| 2017 |
NF-κB is a pivotal mediator of EGF/EGFR-induced FOXC1 transcription; NF-κB-p65 enhances FOXC1 promoter activity and directly binds to the FOXC1 promoter region. Loss or inhibition of NF-κB diminishes FOXC1 expression in basal-like breast cancer cells. |
Luciferase reporter assays, EMSA, biotinylated oligonucleotide precipitation assay, ChIP at the FOXC1 promoter, NF-κB knockdown/inhibition |
Cell communication and signaling : CCS |
Medium |
28629477
|
| 2018 |
FOXC1 directly binds the beta-catenin promoter to activate its transcription, as demonstrated by luciferase reporter and ChIP assays. Overexpression of beta-catenin reverses CSC-like property inhibition by FOXC1 knockdown, and beta-catenin knockdown attenuates FOXC1-induced CSC properties in NSCLC. |
Luciferase reporter assay, ChIP at beta-catenin promoter, FOXC1 KD/OE with beta-catenin rescue/KD epistasis, sphere-formation and tumorigenicity assays |
Journal of experimental & clinical cancer research : CR |
Medium |
30189871
|
| 2018 |
FOXC1 directly binds the promoter region of the FBP1 gene and negatively regulates its transcriptional activity, reprogramming glycolytic metabolism (Warburg effect) to promote colorectal cancer cell proliferation. |
ChIP at FBP1 promoter, luciferase reporter assay, FOXC1 OE/KD with metabolic readouts (glucose consumption, lactate production), in vivo xenograft |
Oncogene |
Medium |
30171256
|
| 2019 |
p38 MAPK phosphorylates FOXC1 at Ser241 and Ser272, maintaining FOXC1 protein stability by inhibiting ubiquitination-mediated degradation. FOXC1 is dephosphorylated by protein phosphatase 2A. Stabilized FOXC1 transcriptionally activates MMP10, SOX4, and SOX13 to promote colorectal cancer metastasis. |
Site-directed mutagenesis of Ser241/272, co-immunoprecipitation of p38-FOXC1, ubiquitination assays, PP2A dephosphorylation assay, ChIP at MMP10 promoter, in vitro and in vivo metastasis assays |
The Journal of pathology |
High |
31650548
|
| 2021 |
FOXC1 and RUNX1 physically interact through their Forkhead and Runt domains, respectively, and co-occupy primed/active enhancers near differentiation genes in AML. FOXC1 stabilizes association of RUNX1, HDAC1, and Groucho repressor TLE3 at these enhancers to suppress their activity; FOXC1 knockdown causes loss of repressor proteins, gain of CEBPA binding, enhancer acetylation, and upregulation of differentiation genes including KLF2, while redistributing RUNX1/TLE3/HDAC1 from enhancers to promoters to repress self-renewal genes MYC and MYB. |
Integrated proteomics (mass spectrometry), ChIP-seq, ATAC-seq, Co-IP of FOXC1-RUNX1 with domain mapping, FOXC1 KD with transcriptomic and epigenomic readouts |
Cell reports |
High |
34551306
|
| 2016 |
FOXC1 expression is regulated by BMP4-induced SMAD activity; SMAD proteins bind the mouse Foxc1 promoter approximately 300 bp upstream of the transcription start site. In progenitor cells, Foxc1 is required for BMP4-induced osteogenic differentiation; its knockdown in preosteoblasts (MC3T3) accelerates osteoblast differentiation and mineralization. |
BMP4 treatment, ChIP demonstrating SMAD binding to Foxc1 promoter, luciferase reporter of SMAD-responsive Foxc1 promoter fragment, siRNA knockdown with osteogenic differentiation assays |
Journal of cellular biochemistry |
Medium |
26666591
|
| 2021 |
FOXC1 governs corneal epithelial fate by directly binding lineage-specific open promoters or enhancers marked by H3K4me2. FOXC1 depletion activates the keratinization pathway and reprograms corneal epithelial cells into skin-like cells, disrupts collagen metabolism and interferon signaling, and causes loss of IRF1 and PAX6 expression. |
ATAC-seq, H3K4me2 ChIP-seq, FOXC1 KD in corneal epithelial cells and patient samples, transcriptomic analysis |
Signal transduction and targeted therapy |
High |
33414365
|
| 2021 |
Foxc1 expression in chondrocytes is directly regulated by SOX9 activity. Foxc1 promotes chondrocyte differentiation; chondrocyte-specific deletion of Foxc1 and Foxc2 disrupts growth plate organization, reduces chondrocyte proliferation, and delays hypertrophy, with genome-wide disruption of chondrogenesis/ossification gene expression. |
SOX9 regulation of Foxc1 promoter, conditional chondrocyte-specific Foxc1/Foxc2 knockout in mice, skeletal phenotyping, differential gene expression (RNA-seq), in vitro chondrogenesis assays in ESCs |
The Journal of biological chemistry |
High |
34331943
|
| 2021 |
Foxc1 promotes chondrogenesis in the face by establishing chromatin accessibility at cartilage-associated gene enhancers co-enriched for Sox9 and Fox binding motifs. In zebrafish lacking Foxc1 paralogs, there is a global decrease in chondrocyte chromatin accessibility coincident with loss of dorsal facial cartilages; transgenesis confirmed that Foxc1-dependent elements function as stage- and region-specific enhancers. |
ATAC-seq during zebrafish neural crest-to-chondrocyte differentiation, Foxc1 mutant zebrafish analysis, transgenic enhancer reporter assays |
eLife |
High |
33501917
|
| 2017 |
FOXC1 loss of function in zebrafish reduces retinal ganglion cell number in the retinal ganglion cell layer and produces a thinner optic nerve. Foxc1 is required for expression of atoh7, a gene necessary for RGC differentiation; markers of differentiated RGCs (pou4f2) are downregulated without increased cell death, indicating a differentiation rather than survival defect. |
CRISPR-induced foxc1b null mutation, morpholino foxc1a knockdown, cell counting in RGC layer, optic nerve thickness measurement, atoh7 and pou4f2 expression analysis |
Vision research |
Medium |
30684501
|
| 2021 |
FOXC1 promotes HCC proliferation and metastasis by transcriptionally upregulating DNMT3B, which induces DNA hypermethylation of the CTH (cystathionine γ-lyase) promoter to silence CTH, thereby inhibiting cysteine metabolism and increasing ROS levels. ROS in turn activates the ERK1/2-ELK1 pathway to further upregulate FOXC1, forming a positive feedback loop. |
Amino acid arrays, ROS measurement assays, bisulfite genomic sequencing, methylation-specific PCR, ChIP (FOXC1 on DNMT3B promoter), luciferase reporter, CTH overexpression/knockdown rescue, in vivo xenograft metastasis |
Journal of experimental & clinical cancer research : CR |
High |
33522955
|
| 2023 |
FOXC1 and FOXC2 directly bind regulatory elements of CXCL12 and RSPO3 loci in blood endothelial cells and lymphatic endothelial cells, respectively. EC/LEC-specific deletion of Foxc1 and/or Foxc2 impairs vascular regrowth after intestinal ischemia-reperfusion and reduces CXCL12 (in BECs) and Wnt activator RSPO3 (in LECs), thereby suppressing Wnt/ISC activation; CXCL12 and RSPO3 treatment rescues intestinal damage in respective mutants. |
EC/LEC-specific conditional Foxc1/Foxc2 knockout mice, intestinal I/R injury model, ChIP at CXCL12 and RSPO3 loci, cytokine/growth factor rescue experiments, Wnt signaling readouts in ISCs |
EMBO reports |
High |
37154714
|
| 2024 |
FOXC1 in vascular endothelial cells transcriptionally regulates Slc3a2 and Slc7a5 (encoding the CD98/LAT1/4F2hc amino acid transporter), which controls intracellular amino acid transport and mTOR activation. EC-specific Foxc1 loss reduces mTOR activity and impairs retinal vascular growth; mTOR agonist MHY-1485 rescues perturbed angiogenesis. Foxc1 is also required for pericyte function in blood-retina barrier formation. |
EC-specific conditional Foxc1 KO mice, retinal flat-mount vascular analysis, Slc3a2/Slc7a5 expression analysis, mTOR activity assay, mTOR agonist rescue, oxygen-induced retinopathy model, pericyte marker analysis |
Nature communications |
High |
38755144
|
| 2015 |
Hypo- and hypermorphic FOXC1 mutations cause dominant glaucoma with remarkable phenotypic variability. Truncating mutations retaining the N-terminal activation domain (p.Y47X, p.Q106X) exhibit hyperactivity (gain-of-function); p.I126S causes partial loss-of-function through impaired protein stability, DNA binding, phosphorylation, and altered subcellular distribution. |
Transcriptional activity assays, protein stability assays, DNA-binding assays, subcellular localization analysis, phosphorylation analysis of patient-derived mutations |
PloS one |
Medium |
25786029
|
| 2019 |
FOXC1 transcriptionally activates TLR3 and TLR4 promoters by direct binding (shown by ChIP), with FOXC1 overexpression/knockdown bidirectionally regulating TLR3/4 mRNA and protein levels. FOXC1 overexpression has pro-inflammatory effects and worsens infarct size and heart function in a mouse myocardial ischemia model. |
In silico TF screening, dual-luciferase reporter for TLR3/4 promoters, ChIP of FOXC1 at TLR3/4 promoters, FOXC1 OE/KD, in vivo mouse MI model with functional cardiac readouts |
Journal of cellular and molecular medicine |
Medium |
31517441
|
| 2021 |
FOXC1 negatively regulates DKK1 expression by binding to its promoter, thereby de-repressing the Wnt signaling pathway. FOXC1 can also form a complex with unphosphorylated β-catenin in the cytoplasm, facilitating β-catenin nuclear translocation to regulate c-MYC expression and promote gastric cancer cell proliferation. |
ChIP at DKK1 promoter, Co-IP of FOXC1-β-catenin complex, luciferase reporter, FOXC1 KD/OE with Wnt pathway readouts and proliferation assays |
Frontiers in cell and developmental biology |
Medium |
33987183
|
| 2023 |
Foxc1 functions as a transcriptional activator of Ubqln1 (ubiquilin-1); Sirt1 promotes Foxc1 expression by deacetylating EZH2 and inhibiting its activity toward the Foxc1 locus. This Sirt1/Foxc1/Ubqln1 axis regulates proteostasis during cerebral ischemia-reperfusion injury. |
Co-IP, ChIP, dual-luciferase reporter assays, siRNA knockdown of Foxc1/Sirt1/Ubqln1, OGD/R and MCAO/R ischemia models |
International immunopharmacology |
Medium |
38452414
|
| 2023 |
FOXC1 overexpression inhibits microglial migration and neuroinflammation in sepsis-associated encephalopathy by increasing IκBα expression, thereby suppressing NF-κB (p65) activation and downstream pro-inflammatory cytokines (IL-1β, TNF-α); IκBα inhibition reverses the Foxc1-mediated effects in vitro. |
FOXC1 OE/KD in BV-2 microglia (LPS model), CLP mouse surgery model, Morris Water Maze cognitive assessment, Western blot (IκBα, p65, cytokines), IκBα inhibitor rescue |
Molecular medicine reports |
Medium |
35103290
|
| 2017 |
FOXC1 directly binds an upstream regulatory region of Fgfr1 and activates an Fgfr1 promoter element to specifically induce expression of the FGFR1-IIIc isoform following TGFβ1-induced EMT, promoting three-dimensional invasive migration that can be rescued by FGFR1 re-expression in FOXC1-knockdown cells. |
RNA-seq (isoform analysis), ChIP at Fgfr1 upstream region, Fgfr1 promoter luciferase reporter, FOXC1 KD/OE, FGFR1 rescue experiment, 3D migration assay |
Molecular cancer research : MCR |
Medium |
28684636
|
| 2020 |
FOXC1 mediates LINC00301 expression in NSCLC by binding to the LINC00301 promoter (validated by ChIP). LINC00301 in turn binds EZH2 (at EZH2 aa 612-727, LINC00301 nt 83-123), causing H3K27me3 at the EAF2 promoter to silence EAF2, which stabilizes pVHL and thereby controls HIF1α levels. |
ChIP (FOXC1 on LINC00301 promoter), RNA pull-down, protein domain mapping, RIP, EMSA, Alpha protein-protein interaction assay, luciferase reporter |
Genome medicine |
Medium |
32878637
|
| 2024 |
Telomere shortening in cardiomyocytes leads to proximal telomeric chromatin decompaction (reduced TAD insulation), increasing FOXC1 accessibility and expression. Overexpression of FOXC1 in hiPSC-CMs induces aging markers, mitochondrial dysfunction, and contractile dysfunction; FOXC1 knockdown rescues these phenotypes. FOXC1 protein levels are negatively correlated with telomere lengths in heart failure patient cardiomyocytes. |
Hi-C (TAD analysis), RNA-seq, isogenic hiPSC-CM model with short vs normal telomeres, FOXC1 OE/KD with mitochondrial function and contractility readouts, patient sample FOXC1/telomere correlation |
Nucleic acids research |
Medium |
38634789
|
| 2016 |
Foxc1 regulates early cardiomyogenesis during a specific differentiation window (D4-D6) in ESC-derived cardiomyocytes, controlling early cardiomyogenic factors Isl1, Mef2c, and Nkx2.5. A novel direct Foxc1 target, Myh7 (MHCβ), was identified, establishing Foxc1 as a regulator of both cardiomyogenic specification and functional cardiomyocyte properties. |
Foxc1 KD/OE in ESC differentiation model, whole-transcriptome RNA-seq, electrophysiological characterization of ESC-derived cardiomyocytes, Myh7 as direct target (RNA-seq + expression analysis) |
Stem cells (Dayton, Ohio) |
Medium |
26824887
|
| 2025 |
Serine deprivation activates ERK1/2-ELK1 signaling to upregulate FOXC1 in colorectal cancer cells. Elevated FOXC1 promotes transcription of serine synthesis pathway enzymes PHGDH, PSAT1, and PSPH, supporting serine biosynthesis and 5-FU resistance through effects on purine metabolism and DNA damage repair. |
ChIP (FOXC1 at PHGDH/PSAT1/PSPH promoters), luciferase reporter, serine deprivation cell culture model, ERK1/2-ELK1 pathway inhibitor studies, 5-FU resistance assays |
Cell communication and signaling : CCS |
Medium |
39773485
|
| 2020 |
EZH2 represses FOXC1 expression by mediating H3K27me3 at the FOXC1 promoter in breast cancer cells. OGT (O-GlcNAc transferase) knockdown alters EZH2 binding to the FOXC1 promoter in a cell-context-dependent manner and is associated with increased histone H3 acetylation at the FOXC1 locus, modulating FOXC1 expression. |
ChIP (EZH2 and OGT at FOXC1 promoter), EZH2 inhibitor treatment (DZNeP, GSK343), OGT siRNA knockdown, H3K27me3 and H3 acetylation analysis |
Acta pharmacologica Sinica |
Medium |
33057161
|
| 2023 |
Icaritin inhibits endometrial cancer cell proliferation by suppressing O-GlcNAc modification (O-GlcNAcylation) of FOXC1, thereby reducing FOXC1 protein stability and activity. |
Western blot for O-GlcNAcylated FOXC1, icaritin treatment, FOXC1 KD/OE in cell proliferation/invasion assays, xenograft tumor model |
Phytomedicine |
Low |
37683586
|