TCF-4 Cancer Research Results

TCF-4, Transcription Factor 4: Click to Expand ⟱
Source:
Type:
TCF4 gene (Transcription Factor 4) is a transcription factor that plays a crucial role in the Wnt/β-catenin signaling pathway, which is involved in cell proliferation, differentiation, and survival.
TCF4 gene has been found to be:
     Amplified in 15% of breast cancer cases
     Mutated in 10% of lung cancer cases
     Deleted in 20% of prostate cancer cases
     Methylated in 30% of colorectal cancer cases
Scientific Papers found: Click to Expand⟱
1012- EGCG,    Inhibition of beta-catenin/Tcf activity by white tea, green tea, and epigallocatechin-3-gallate (EGCG): minor contribution of H(2)O(2) at physiologically relevant EGCG concentrations
- in-vitro, Nor, HEK293
*H2O2↑,
*β-catenin/ZEB1↓,
*TCF-4↓,

2839- FIS,    Dietary flavonoid fisetin for cancer prevention and treatment
- Review, Var, NA
DNAdam↑, Fisetin induced DNA fragmentation, ROS generation, and apoptosis in NCI-H460 cells via a reduction in Bcl-2 and increase in Bax expression
ROS↑,
Apoptosis↑,
Bcl-2↓,
BAX↑,
cl‑Casp9↑, Fisetin treatment increased cleavage of caspase-9 and caspase-3 thereby increasing caspase-3 activation
cl‑Casp3↑,
Cyt‑c↑, leading to cytochrome-c release
lipid-P↓, Fisetin (25 mg/kg body weight) decreased histological lesions and levels of lipid peroxidation and modulated the enzymatic and nonenzymatic anti-oxidants in B(a)P-treated Swiss Albino mice
TumCG↓, We observed that fisetin treatment (5–20 μM) inhibits cell growth and colony formation in A549 NSC lung cancer cells.
TumCA↓, Another study showed that fisetin inhibits adhesion, migration, and invasion in A549 lung cancer cells by downregulating uPA, ERK1/2, and MMP-2
TumCMig↓,
TumCI↓,
uPA↓,
ERK↓,
MMP9↓,
NF-kB↓, Treatment with fisetin also decreased the nuclear levels of NF-kB, c-Fos, c-Jun, and AP-1 and inhibited NF-kB binding.
cFos↓,
cJun↓,
AP-1↓,
TumCCA↑, Our laboratory has previously shown that treatment of LNCaP cells with fisetin caused inhibition of PCa by G1-phase cell cycle arrest
AR↓, inhibited androgen signaling and tumor growth in athymic nude mice
mTORC1↓, induced autophagic cell death in PCa cells through suppression of mTORC1 and mTORC2
mTORC2↓,
TSC2↑, activated the mTOR repressor TSC2, commonly associated with inhibition of Akt and activation of AMPK
EGF↓, Fisetin also inhibits EGF and TGF-β induced YB-1 phosphorylation and EMT in PCa cells
TGF-β↓,
EMT↓, Fisetin also inhibits EGF and TGF-β induced YB-1 phosphorylation and EMT in PCa cells
P-gp↓, decrease the P-gp protein in multidrug resistant NCI/ADR-RES cells.
PI3K↓, Fisetin also inhibited the PI3K/AKT/NFkB signaling
Akt↓,
mTOR↓, Fisetin inhibited melanoma progression in a 3D melanoma skin model with downregulation of mTOR, Akt, and upregulation of TSC
eff↑, combinational treatment study of melatonin and fisetin demonstrated enhanced antitumor activity of fisetin
ROS↓, Fisetin inhibited ROS and augmented NO generation in A375 melanoma cells
ER Stress↑, induction of ER stress evidenced by increased IRE1α, XBP1s, ATF4, and GRP78 levels in A375 and 451Lu cells.
IRE1↑,
ATF4↑,
GRP78/BiP↑,
ChemoSen↑, combination of fisetin with sorafenib effectively inhibited EMT and augmented the anti-metastatic potential of sorafenib by reducing MMP-2 and MMP-9 proteins in melanoma cell xenografts
CDK2↓, Fisetin (0–60 μM) was shown to inhibit activity of CDKs dose-dependently leading to cell cycle arrest in HT-29 human colon cancer cells
CDK4↓, Fisetin treatment decreased activities of CDK2 and CDK4 via decreased levels of cyclin-E, cyclin-D1 and increase in p21 (CIP1/WAF1) levels.
cycE/CCNE↓,
cycD1/CCND1↓,
P21↑,
COX2↓, fisetin (30–120 μM) induces apoptosis in colon cancer cells by inhibiting COX-2 and Wnt/EGFR/NF-kB -signaling pathways
Wnt↓,
EGFR↓,
β-catenin/ZEB1↓, Fisetin treatment inhibited Wnt/EGFR/NF-kB signaling via downregulation of β-catenin, TCF-4, cyclin D1, and MMP-7
TCF-4↓,
MMP7↓,
RadioS↑, fisetin treatment was found to radiosensitize human colorectal cancer cells which are resistant to radiotherapy
eff↑, Combined treatment of fisetin with NAC increased cleaved caspase-3, PARP, reduced mitochondrial membrane potential with induction of caspase-9 in COLO25 cells

2832- FIS,    Fisetin's Promising Antitumor Effects: Uncovering Mechanisms and Targeting for Future Therapies
- Review, Var, NA
MMP↓, fraction of cells with reduced mitochondrial membrane potential also increased, indicating that fisetin-induced apoptosis also destroys mitochondria.
mtDam↑,
Cyt‑c↑, Cytochrome c and Smac/DIABLO levels are also released when the mitochondrial membrane potential changes, and this results in the activation of the caspase cascade and the cleavage of poly [ADP-ribose] polymerase (PARP)
Diablo↑,
Casp↑,
cl‑PARP↑,
Bak↑, Fisetin induced apoptosis in HCT-116 human colon cancer cells by upregulating proapoptotic proteins Bak and BIM and downregulating antiapoptotic proteins B cell lymphoma (BCL)-XL and -2.
BIM↑,
Bcl-xL↓,
Bcl-2↓,
P53↑, fisetin through the activation of p53
ROS↑, over generation of ROS, which is also directly initiated by fisetin, the stimulation of AMPK
AMPK↑,
Casp9↑, activating caspase-9 collectively, then activating caspase-3, leading to apopotosis
Casp3↑,
BID↑, Bid, AIF and the increase of the ratio of Bax to Bcl-2, causing the activation of caspase 3–9
AIF↑,
Akt↓, The inhibition of the Akt/mTOR/MAPK/
mTOR↓,
MAPK↓,
Wnt↓, Fisetin has been shown to degrade the Wnt/β/β-catenin signal
β-catenin/ZEB1↓,
TumCCA↑, fisetin triggered G1 phase arrest in LNCaP cells by activating WAF1/p21 and kip1/p27, followed by a reduction in cyclin D1, D2, and E as well as CDKs 2, 4, and 6
P21↑,
p27↑,
cycD1/CCND1↓,
cycE/CCNE↓,
CDK2↓,
CDK4↓,
CDK6↓,
TumMeta↓, reduces PC-3 cells' capacity for metastasis
uPA↓, fisetin decreased MMP-2 protein, messenger RNA (mRNA), and uPA levels through an ERK-dependent route
E-cadherin↑, Fisetin can upregulate the epithelial marker E-cadherin, downregulate the mesenchymal marker vimentin, and drastically lower the EMT regulator twist protein level at noncytotoxic dosages, studies have revealed.
Vim↓,
EMT↓,
Twist↓,
DNAdam↑, Fisetin induces apoptosis in the human nonsmall lung cancer cell line NCI-H460, which causes DNA breakage, the growth of sub-G1 cells, depolarization of the mitochondrial membrane, and activation of caspases 9, 3, which are involved in prod of iROS
ROS↓, fisetin therapy has been linked to a reduction in ROS, according to other research.
COX2↓, Fisetin lowered the expression of COX-1 protein, downregulated COX-2, and decreased PGE2 production
PGE2↓,
HSF1↓, Fisetin is a strong HSF1 inhibitor that blocks HSF1 from binding to the hsp70 gene promoter.
cFos↓, NF-κB, c-Fos, c-Jun, and AP-1 nuclear levels were also lowered by fisetin treatment
cJun↓,
AP-1↓,
Mcl-1↓, inhibition of Bcl-2 and Mcl-1 all contribute to an increase in apoptosis
NF-kB↓, Fisetin's ability to prevent NF-κB activation in LNCaP cells
IRE1↑, fisetin (20–80 µM) was accompanied by brief autophagy and the production of ER stress, which was shown by elevated levels of IRE1 α, XBP1s, ATF4, and GRP78 in A375 and 451Lu cells
ER Stress↑,
ATF4↑,
GRP78/BiP↑,
MMP2↓, lowering MMP-2 and MMP-9 proteins in melanoma cell xenografts
MMP9↓,
TCF-4↓, fisetin therapy reduced levels of β-catenin, TCF-4, cyclin D1, and MMP-7,
MMP7↓,
RadioS↑, fisetin treatment could radiosensitize human colorectal cancer cells that are resistant to radiotherapy.
TOP1↓, fisetin blocks DNA topoisomerases I and II in leukemia cells.
TOP2↓,

1989- PTL,    Parthenolide and Its Soluble Analogues: Multitasking Compounds with Antitumor Properties
- Review, Var, NA
eff↑, therapeutical potential of PN has been increased by chemical design and synthesis of more soluble analogues including dimethylaminoparthenolide (DMAPT).
NF-kB↓, these compounds not only inhibit prosurvival transcriptional factors such as NF-κB and STATs
STAT↓,
ROS↑, increasing intracellular reactive oxygen species (ROS) production
Inflam↓, anti-inflammatory action of PN has been widely considered a consequence of its inhibitory effect on the transcription factors belonging to NF-κB family
Wnt↓, PN was recently shown to inhibit Wnt signaling by decreasing the levels of the transcription factors TCF4/LEF1
TCF-4↓,
LEF1↓,
GSH↓, Wen et al., who found that PN-induced apoptosis in hepatoma cells was accompanied with depletion of glutathione (GSH), generation of ROS, reduction of mitochondrial transmembrane potential and activation of caspases.
MMP↓,
Casp↑,
eff↓, These effects were effectively abrogated by the antioxidant N-acetyl-l-cysteine (NAC) and enhanced by the GSH synthesis inhibitor buthionine sulfoximine (BSO) confirming the role of oxidative stress in PN-induced apoptosis
CSCs↓, several studies showing the effect of PN in reducing the presence of CSCs in solid and hematological tumors


Showing Research Papers: 1 to 4 of 4

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 4

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

GSH↓, 1,   lipid-P↓, 1,   ROS↓, 2,   ROS↑, 3,  

Mitochondria & Bioenergetics ⓘ

AIF↑, 1,   EGF↓, 1,   MMP↓, 2,   mtDam↑, 1,  

Core Metabolism/Glycolysis ⓘ

AMPK↑, 1,  

Cell Death ⓘ

Akt↓, 2,   Apoptosis↑, 1,   Bak↑, 1,   BAX↑, 1,   Bcl-2↓, 2,   Bcl-xL↓, 1,   BID↑, 1,   BIM↑, 1,   Casp↑, 2,   Casp3↑, 1,   cl‑Casp3↑, 1,   Casp9↑, 1,   cl‑Casp9↑, 1,   Cyt‑c↑, 2,   Diablo↑, 1,   MAPK↓, 1,   Mcl-1↓, 1,   p27↑, 1,  

Kinase & Signal Transduction ⓘ

TSC2↑, 1,  

Transcription & Epigenetics ⓘ

cJun↓, 2,  

Protein Folding & ER Stress ⓘ

ER Stress↑, 2,   GRP78/BiP↑, 2,   HSF1↓, 1,   IRE1↑, 2,  

DNA Damage & Repair ⓘ

DNAdam↑, 2,   P53↑, 1,   cl‑PARP↑, 1,  

Cell Cycle & Senescence ⓘ

CDK2↓, 2,   CDK4↓, 2,   cycD1/CCND1↓, 2,   cycE/CCNE↓, 2,   P21↑, 2,   TumCCA↑, 2,  

Proliferation, Differentiation & Cell State ⓘ

cFos↓, 2,   CSCs↓, 1,   EMT↓, 2,   ERK↓, 1,   mTOR↓, 2,   mTORC1↓, 1,   mTORC2↓, 1,   PI3K↓, 1,   STAT↓, 1,   TCF-4↓, 3,   TOP1↓, 1,   TOP2↓, 1,   TumCG↓, 1,   Wnt↓, 3,  

Migration ⓘ

AP-1↓, 2,   E-cadherin↑, 1,   LEF1↓, 1,   MMP2↓, 1,   MMP7↓, 2,   MMP9↓, 2,   TGF-β↓, 1,   TumCA↓, 1,   TumCI↓, 1,   TumCMig↓, 1,   TumMeta↓, 1,   Twist↓, 1,   uPA↓, 2,   Vim↓, 1,   β-catenin/ZEB1↓, 2,  

Angiogenesis & Vasculature ⓘ

ATF4↑, 2,   EGFR↓, 1,  

Barriers & Transport ⓘ

P-gp↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 2,   Inflam↓, 1,   NF-kB↓, 3,   PGE2↓, 1,  

Hormonal & Nuclear Receptors ⓘ

AR↓, 1,   CDK6↓, 1,  

Drug Metabolism & Resistance ⓘ

ChemoSen↑, 1,   eff↓, 1,   eff↑, 3,   RadioS↑, 2,  

Clinical Biomarkers ⓘ

AR↓, 1,   EGFR↓, 1,  
Total Targets: 86

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

H2O2↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

TCF-4↓, 1,  

Migration ⓘ

β-catenin/ZEB1↓, 1,  
Total Targets: 3

Scientific Paper Hit Count for: TCF-4, Transcription Factor 4
2 Fisetin
1 EGCG (Epigallocatechin Gallate)
1 Parthenolide
Query results interpretion may depend on "conditions" listed in the research papers.
Such Conditions may include : 
  -low or high Dose
  -format for product, such as nano of lipid formations
  -different cell line effects
  -synergies with other products 
  -if effect was for normal or cancerous cells

Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:%  Target#:967  State#:%  Dir#:1
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