TFE3 Cancer Research Results

TFE3, Transcription Factor E3: Click to Expand ⟱
Source:
Type:

TFE3 - Transcription Factor E3

Type: MiT/TFE-family transcription factor / autophagy-lysosome regulator

Function: TFE3 is a transcription factor that regulates lysosomal biogenesis, autophagy, nutrient sensing, mitochondrial and metabolic adaptation, and cellular stress responses. Under nutrient-rich conditions, mTORC1-dependent phosphorylation promotes cytoplasmic retention of TFE3. During starvation or lysosomal stress, TFE3 translocates to the nucleus and activates CLEAR-network genes involved in lysosomal and autophagic function.

Cancer: ↑ Frequently activated or overexpressed in selected cancers and can promote tumor-cell survival, metabolic adaptation, autophagy, lysosomal function, invasion, migration, and treatment resistance. TFE3 gene fusions are oncogenic drivers in TFE3-rearranged renal cell carcinoma. However, MiT/TFE signaling can have context-dependent tumor-suppressive effects in some tissues.

Alzheimer's Disease: ↕ Context-dependent. TFE3 activation can promote autophagy and lysosomal biogenesis and enhance clearance of pathogenic proteins, which is potentially neuroprotective. However, increased TFE3/autophagy signaling can also occur as a compensatory response in Alzheimer's disease when downstream lysosomal clearance remains impaired, so TFE3 expression alone does not directly indicate effective autophagic flux.
Scientific Papers found: Click to Expand⟱
8027- IVM,    Progress in Understanding the Molecular Mechanisms Underlying the Antitumour Effects of Ivermectin
- Review, Var, NA
*AntiP↑, Ivermectin was soon adopted in 1987 as a human medicine that was originally used for the treatment of onchocerciasis, a parasitic infection.
TumCD↑, Ivermectin causes cell death in cancer cell lines by inducing PAK1-mediated cytostatic autophagy,
PAK1↑,
TumAuto↑,
Casp↑, caspase-dependent apoptosis and immunogenic cell death (ICD) through the modulation of some pathways, including the WNT-T cell factor (TCF), Hippo and Akt/mTOR pathways.
ICD↑,
TCF↝, Ivermectin Serves as a WNT-T Cell Factor (TCF) Pathway Response Blocker
Hippo↓,
Akt↓, Ivermectin inhibits the Akt/mTOR signalling pathway by increasing the ubiquitination-mediated degradation of PAK1,
mTOR↓,
angioG↓, In addition, ivermectin induces the multidrug resistance protein (MDR), has potent anti-mitotic activity, targets angiogenesis and inhibits cancer stem-like cells (CSCs).
CSCs↓, Ivermectin Is an Inhibitor of CSCs
MMP↓, collapse of the mitochondrial membrane potential (ΔΨm) and the release of cytochrome c,
Cyt‑c↑,
Apoptosis↑, ivermectin induces apoptosis in glioblastoma and HeLa cells by enhancing cytochrome c release, upregulating Bax and p53 expression, downregulating Bcl-2 expression and decreasing the levels of cyclin E, cyclin D1, CDK2, CDK6 and CDK4
BAX↑,
P53↑,
Bcl-2↓,
cycE/CCNE↓,
cycD1/CCND1↓,
CDK2↓,
CDK6↓,
CDK4↓,
YAP/TEAD↓, Ivermectin Inhibits Proliferation by Inhibiting Yea-Associated Protein 1 (YAP1)
TFE3↑, Ivermectin treatment increases TFE3(Ser321) dephosphorylation, activates TFE3 nuclear translocation and stimulates activation of the TFE3 reporter in human melanoma cells
mTORC1↓, Ivermectin treatment also clearly decreases phosphorylation of the mTORC1 substrate p-70S6K, which results in induction of mTORC1 deactivation.
mitResp↓, Ivermectin Inhibits Mitochondrial Respiration
OCR↓, inhibitory effect of ivermectin on the basal oxygen consumption rate (OCR) and maximum OCR in U87, T98G
compI↓, ivermectin inhibits mitochondrial respiration by decreasing the activity of respiratory complex I enzyme
MMP↓, ivermectin decreased the mitochondrial membrane potential,
ROS↑, Consistently, obviously increased levels of ROS and mitochondrial superoxide as well as decreased ATP levels were also found in glioblastoma, HBMECs and chronic myeloid leukaemia (CML) cells treated with ivermectin
SOD2↑,
ATP↓,
eff↓, (ALCAR, a mitochondrial fuel) and N-acetyl-l-cysteine (NAC, an antioxidant) reversed the inhibitory effects of ivermectin in renal cell carcinoma (RCC) cells, which indicates that mitochondria are the target of ivermectin.
mitA↓, Ivermectin Exerts Anti-Mitotic Activity
P-gp/ABCB1↓, Ivermectin Is a P-Glycoprotein (P-Gp) Inhibitor
TumVol↓, After 10 to 42 days, treatment with ivermectin can reduced the tumour volume by more than 50%.

8040- IVM,    Ivermectin, a potential anticancer drug derived from an antiparasitic drug
- Review, Var, NA
Akt↓, inhibition by IVM of the Akt/mTOR pathway to induce autophagy and p-21-activated kinase 1(PAK1)was the target of IVM for breast cancer
mTOR↓,
TumAuto↑,
TumCP↓, IVM could inhibit the proliferation of the canine breast tumor cell lines CMT7364 and CIPp by blocking the cell cycle without increasing apoptosis, and the mechanism of IVM may be related to the inhibition of the Wnt pathway
TumCCA↑,
Wnt↓,
YAP/TEAD↓,
MMP↓, IVM could significantly reduce the mitochondrial membrane potential and inhibit mitochondrial respiration and ATP production.
mitResp↓,
ATP↓,
eff↓, acetyl-L-cysteine (NAC), could reverse IVM-induced inhibition
eff↑, it was found that IVM could enhance the drug activity of the anti-androgen drug enzalutamide in the prostate cancer cell line LNCaP and reverse the resistance of the prostate cancer cell line PC3 to docetaxel
ROS↑, induction of reactive oxygen species (ROS) production.
ChemoSen↑, IVM can enhance the efficacy of cisplatin to improve the treatment of epithelial ovarian cancer, and the mechanism is related to the inhibition of the Akt/mTOR pathway
PAK1↓, IVM also had a cytotoxic effect on a variety of nasopharyngeal cancer cells in vitro, and the mechanism is related to the reduction of PAK1 kinase activity to inhibit the MAPK pathway.
MAPK↓,
EMT↓, IVM could reduce the metastasis of lung cancer cells by inhibiting EMT.
Beclin-1/ATG6↑, IVM in the breast cancer cell lines MCF-7 and MDA-MB-231 significantly increased intracellular autophagic flux and the expression of key autophagy proteins such as LC3, Bclin1, Atg5
ATG5↑,
CSCs↓, Further studies showed that IVM could inhibit CSCs by regulating the PAK1-STAT3 axis
STAT3↝,
P-gp/ABCB1↓, Several studies have confirmed that IVM could reverse drug resistance by inhibiting P-gp and MDR-associated proteins
MDR1↓,
HSP27↓, Inhibit HSP27 Prostate cancer, Lung cancer Colorectal cancer
Chl↑, Activate chloride channels Leukemia
TFE3↑, Increase TFE3 Activity Melanoma


Showing Research Papers: 1 to 2 of 2

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 2

Pathway results for Effect on Cancer / Diseased Cells:


NA, unassigned(tgid=0) ⓘ

TFE3↑, 2,  

Redox & Oxidative Stress(tgid=1) ⓘ

compI↓, 1,   ICD↑, 1,   ROS↑, 2,   SOD2↑, 1,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

ATP↓, 2,   mitResp↓, 2,   MMP↓, 3,   OCR↓, 1,  

Cell Death(tgid=5) ⓘ

Akt↓, 2,   Apoptosis↑, 1,   BAX↑, 1,   Bcl-2↓, 1,   Casp↑, 1,   Cyt‑c↑, 1,   Hippo↓, 1,   MAPK↓, 1,   TumCD↑, 1,   YAP/TEAD↓, 2,  

Protein Folding & ER Stress(tgid=8) ⓘ

HSP27↓, 1,  

Autophagy & Lysosomes(tgid=9) ⓘ

ATG5↑, 1,   Beclin-1/ATG6↑, 1,   TumAuto↑, 2,  

DNA Damage & Repair(tgid=10) ⓘ

P53↑, 1,  

Cell Cycle & Senescence(tgid=11) ⓘ

CDK2↓, 1,   CDK4↓, 1,   cycD1/CCND1↓, 1,   cycE/CCNE↓, 1,   mitA↓, 1,   TumCCA↑, 1,  

Proliferation, Differentiation & Cell State(tgid=12) ⓘ

CSCs↓, 2,   EMT↓, 1,   mTOR↓, 2,   mTORC1↓, 1,   STAT3↝, 1,   TCF↝, 1,   Wnt↓, 1,  

Migration(tgid=13) ⓘ

Chl↑, 1,   PAK1↓, 1,   PAK1↑, 1,   TumCP↓, 1,  

Angiogenesis & Vasculature(tgid=14) ⓘ

angioG↓, 1,  

Barriers & Transport(tgid=15) ⓘ

P-gp/ABCB1↓, 2,  

Hormonal & Nuclear Receptors(tgid=20) ⓘ

CDK6↓, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

ChemoSen↑, 1,   eff↓, 2,   eff↑, 1,   MDR1↓, 1,  

Functional Outcomes(tgid=23) ⓘ

TumVol↓, 1,  
Total Targets: 49

Pathway results for Effect on Normal Cells:


NA, unassigned(tgid=0) ⓘ

AntiP↑, 1,  
Total Targets: 1

Scientific Paper Hit Count for: TFE3, Transcription Factor E3
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#:1750  State#:%  Dir#:2
  wNotes=on  sortOrder:rid,rpid

 

Home Page