TNFRSF25/DR3/APO3/LARD/TRAMP/WSL1 Cancer Research Results

TNFRSF25/DR3/APO3/LARD/TRAMP/WSL1, - Tumor Necrosis Factor Receptor Superfamily Member 25 / Death Receptor 3: Click to Expand ⟱
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TNFRSF25 - Tumor Necrosis Factor Receptor Superfamily Member 25 / Death Receptor 3

Abbreviation: TNFRSF25, DR3

Alternative Names: Death Receptor 3, APO-3, LARD, TRAMP, WSL-1, TR3

Type: Tumor necrosis factor receptor superfamily member / death receptor / immune signaling receptor

Function: DR3 is a type I transmembrane receptor containing an intracellular death domain. Its principal ligand is TL1A/TNFSF15. DR3 signaling can recruit adaptor proteins including TRADD and activate caspase-dependent apoptosis, necroptosis, NF-κB, JNK, and immune-cell activation pathways.

Cancer: ↕ Context-dependent. DR3 activation can induce apoptosis or necroptosis in cancer cells and can enhance antitumor immune responses. However, DR3 can also activate NF-κB-dependent survival or inflammatory signaling, and certain splice variants have been associated with invasion and metastasis in selected cancers.

Favorable Direction in Cancer: Context-dependent. ↑ DR3 death-signaling can be favorable where it promotes apoptosis or necroptosis, whereas ↓ DR3 signaling may be favorable in tumors where DR3 promotes survival, inflammation, invasion, or metastasis.

Interpretation Note: Do not confuse DR3/TNFRSF25 with DcR3/TNFRSF6B. DcR3 is a soluble decoy receptor and is a distinct target.
Scientific Papers found: Click to Expand⟱
8235- LCA,    Anticancer effects of licochalcones: A review of the mechanisms
- Review, Var, NA
mt-Apoptosis↑, licochalcones can activate the mitochondrial apoptosis pathway and the death receptor pathway, promote autophagy-related protein expression, inhibit cell cycle protein expression,
TumAuto↑,
TumCMig↓, regulate cancer migration-related protein expression via multiple signaling pathways, including EGFR/ERK, PI3K/Akt/mTOR, p38/JNK, JAK2/STAT3, MEK/ERK, Wnt/β-catenin, and MKK4/JNK signaling pathways.
LC3‑Ⅱ/LC3‑Ⅰ↑, increasing the LC3-II/LC3-I ratio, as well as the levels of the autophagy-related proteins ATG5, ATG7, and P62.
ATG5↑,
ATG7↑,
p62↑,
CHOP/DDIT3↑, LA-induced increases in CHOP expression also promote autophagy
ER Stress↑, LA-induced autophagy in lung cancer cells is associated with the induction of endoplasmic reticulum stress
UPR↑, LA (10 μM) enhances the expression of miR-144-3p, causes unfolded protein response,
ATG3↑, triggers autophagy by promoting the accumulation and expression of ATG1, ATG3, ATG6, and ATG16 via activation of the PERK/ATF4/CHOP signaling pathway
Beclin-1/ATG6↑,
ATG16L1↑,
PERK↑,
ATF4↑,
ATP↓, LA (2.5–25 μM) inhibited ATP production and caused mitochondrial dysfunction in H1299 and H322 lung cancer cells by inhibiting hypoxia-induced HIF-1α accumulation and the expression of target genes GLUT1 and PDK1
Hif1a↓,
GLUT1↓,
PDK1 / PDPK1↓,
Bcl-xL↓, induce apoptosis in H460 and A549 lung cancer cells by decreasing the levels of Bcl-xL and Bcl-2 while increasing the levels of Bad, Bax, cleaved PARP, and caspase-3
Bcl-2↓,
BAD↑,
BAX↑,
Casp3↑,
survivin↓, LA (5–50 μM) downregulated the expression of survivin by inhibiting the EGFR signaling pathway and its downstream kinases ERK1/2 and AKT in H3255, HCC827, H1975, and A549 lung cancer cells
EGFR↓,
ERK↓,
Akt↓,
mtDam↑, LB (5–15 μM) inhibited the EGFR and MET signaling pathways and induced mitochondrial dysfunction and endoplasmic reticulum stress in HCC827 lung cancer cells, which induced the loss of MMP, release of cytochrome c, and increased expression of casp
MMP↓,
Cyt‑c↑,
Casp↑,
MDM2↓, By inhibiting the expression of MDM2, cyclin B1, CDC2, and CDC25C, LA (10–15 μM) led to cell cycle arrest of H460 and A549 lung cancer cells at the G2/M phase
CycB/CCNB1↓,
CDC2↓,
CDC25↓,
TumCCA↑,
TumCP↓, decreases in the proliferation of lung cancer cells by LA were related to the inhibition of the Wnt/β-catenin signaling pathway
Wnt↓,
β-catenin/ZEB1↓,
Sp1/3/4↓, LA (2–20 μM) inhibited the AKT signaling pathway and the expression of the downstream transcription factor Sp1, which reduced the levels of MMP-1 and MMP-3 and inhibited the migration and invasion of A549 and H460 lung cancer cells
MMP-10↓,
MMP3↓,
TumCI↓,
Imm↑, Activation of the immune system
PD-L1↓, LA (10–50 μM) inhibited the expression of PD-L1 and thereby induced the production of reactive oxygen species (ROS) in A549 lung cancer cells, which inhibited the phosphorylation of 4EBP1, activated the PERK/eIF2α pathway,
ROS↑,
4E-BP1↓,
eIF2α↓,
PI3K↓, By inhibiting the PI3K/Akt/mTOR signaling pathway, LA (5–20 μM) activated the mitochondrial apoptosis pathway
mTOR↓,
p‑cMET↑, LA (1–50 μM) induced endoplasmic reticulum stress in HepG2 cells by inducing phosphorylation of VEGFR2, c-Met receptor, and PLCγ1 and enhancing the cytosolic Ca2+ release from the endoplasmic reticulum, which subsequently induced ROS accumulation
Ca+2↑,
RUBCN↓, LA-induced (5–50 μM) downregulation of PDK1 and rubicon by activating the ULK1/Atg13 signaling pathway and increasing the expression of TSC1/2, PRAS40, CTMP, and PP2A.
ATG13↑,
TSC1↑,
TSC2↑,
PRAS40↑,
PP2A↑,
ULK1/ATG1↑,
THEM4/CTMP↑,
DR5↑, LA activates the death receptor pathway and caspase cascade by increasing the expression of DR3, DR5, and Fas.
Fas↑,
TNFRSF25/DR3/APO3/LARD/TRAMP/WSL1↑,
PKCδ↓, LA also decreases the expression of the survival factor PKCε, p70S6K, and Akt.
P70S6K↓,
VEGF↓, Via downregulation of VEGF-A, LE (7–14 mg/kg) inhibited angiogenesis in cancer tissue in a xenograft mouse model using MDA-MB 231 breast cancer cells
angioG↓,
HK2↓, Moreover, the inhibitory effect of LA (10–50 μM) on the AKT signaling pathway can downregulate the expression of hexokinase 2A and inhibit glycolysis, thereby inducing apoptosis of MKN45 and SGC7901 cells
Glycolysis↓,
TrxR1↓, LA (10–40 μM) can enhance the production of intracellular ROS by inhibiting the expression of thioredoxin reductase-1, which activates the mitochondrial apoptosis pathway and induces apoptosis in HCT-116 cells
APAF1↑, By increasing intracellular Ca2+ and ROS levels, decreasing mitochondrial membrane potential, upregulating Apaf-1, caspase-9, caspase-3, and cleaved PARP levels, and elevating the Bax/Bcl-2 ratio, LA (10–80 μM) induced T24 cells apoptosis
cl‑PARP↑,
Bax:Bcl2↑,
ABCG2↓, By reducing the expression of BCRP, LA (10–100 μM) reduced the BCRP-mediated efflux of doxorubicin and temozolomide in BCRP-MDCKII cells.
BioEnh↑, Inhibition of BCRP expression can promote increased intestinal (re)uptake of antineoplastic drugs and decrease their hepatic metabolization, thereby enhancing their bioavailability.

8244- LCA,    Licochalcone A from licorice root, an inhibitor of human hepatoma cell growth via induction of cell apoptosis and cell cycle arrest
- in-vitro, Liver, HepG2
TumCP↓, LCA inhibited the proliferation of HepG2 cells with IC50 (65.96 μM) for 24 h and IC50 (44.13 μM) for 48 h and caused significant morphological changes and also led to intracellular ROS generation.
ROS↑,
TumCCA↑, LCA affected HepG2 cell growth by terminating cell cycle development at G2/M transition and further induced the apoptosis process.
Apoptosis↑,
survivin↓, The mRNA expression of genes involved in cell cycles such as Survivin, Cyclin B1, and CDK1 were reduced
CycB/CCNB1↓,
CDK1↓,
WEE1↑, while, Weel, P21, Cyclin D1, and JNK1 showed increased mRNA expression.
P21↑,
cycD1/CCND1↑,
JNK↑,
TNFRSF25/DR3/APO3/LARD/TRAMP/WSL1↑, The anti-cancer action involved increased mRNA expression of DR3, DR5, caspases-3, caspases-8, caspases-10, Fas, Bad, Bax, Bcl-2, Bak, and PUMA
DR5↑,
Casp3↑,
Casp8↑,
Casp10↑,
Fas↑,
BAD↑,
BAX↑,
PUMA↑,
PKCδ↓, besides, decreased level of PKCε, p70S6K, and Akt.
P70S6K↓,
Akt↓,


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) ⓘ

ATG13↑, 1,   ATG16L1↑, 1,   RUBCN↓, 1,   THEM4/CTMP↑, 1,   TNFRSF25/DR3/APO3/LARD/TRAMP/WSL1↑, 2,   ULK1/ATG1↑, 1,   WEE1↑, 1,  

Redox & Oxidative Stress(tgid=1) ⓘ

ROS↑, 2,   TrxR1↓, 1,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

ATP↓, 1,   CDC2↓, 1,   CDC25↓, 1,   MMP↓, 1,   mtDam↑, 1,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

ATG7↑, 1,   Glycolysis↓, 1,   HK2↓, 1,   PDK1 / PDPK1↓, 1,  

Cell Death(tgid=5) ⓘ

Akt↓, 2,   APAF1↑, 1,   Apoptosis↑, 1,   mt-Apoptosis↑, 1,   BAD↑, 2,   BAX↑, 2,   Bax:Bcl2↑, 1,   Bcl-2↓, 1,   Bcl-xL↓, 1,   Casp↑, 1,   Casp10↑, 1,   Casp3↑, 2,   Casp8↑, 1,   Cyt‑c↑, 1,   DR5↑, 2,   Fas↑, 2,   JNK↑, 1,   MDM2↓, 1,   PUMA↑, 1,   survivin↓, 2,  

Kinase & Signal Transduction(tgid=6) ⓘ

Sp1/3/4↓, 1,   TSC2↑, 1,  

Protein Folding & ER Stress(tgid=8) ⓘ

CHOP/DDIT3↑, 1,   eIF2α↓, 1,   ER Stress↑, 1,   PERK↑, 1,   UPR↑, 1,  

Autophagy & Lysosomes(tgid=9) ⓘ

ATG3↑, 1,   ATG5↑, 1,   Beclin-1/ATG6↑, 1,   LC3‑Ⅱ/LC3‑Ⅰ↑, 1,   p62↑, 1,   TumAuto↑, 1,  

DNA Damage & Repair(tgid=10) ⓘ

cl‑PARP↑, 1,  

Cell Cycle & Senescence(tgid=11) ⓘ

CDK1↓, 1,   CycB/CCNB1↓, 2,   cycD1/CCND1↑, 1,   P21↑, 1,   TumCCA↑, 2,  

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

4E-BP1↓, 1,   p‑cMET↑, 1,   ERK↓, 1,   mTOR↓, 1,   P70S6K↓, 2,   PI3K↓, 1,   Wnt↓, 1,  

Migration(tgid=13) ⓘ

Ca+2↑, 1,   MMP-10↓, 1,   MMP3↓, 1,   PKCδ↓, 2,   TSC1↑, 1,   TumCI↓, 1,   TumCMig↓, 1,   TumCP↓, 2,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature(tgid=14) ⓘ

angioG↓, 1,   ATF4↑, 1,   EGFR↓, 1,   Hif1a↓, 1,   VEGF↓, 1,  

Barriers & Transport(tgid=15) ⓘ

GLUT1↓, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

Imm↑, 1,   PD-L1↓, 1,  

Protein Aggregation(tgid=19) ⓘ

PP2A↑, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

ABCG2↓, 1,   BioEnh↑, 1,  

Clinical Biomarkers(tgid=22) ⓘ

EGFR↓, 1,   PD-L1↓, 1,  

Functional Outcomes(tgid=23) ⓘ

PRAS40↑, 1,  
Total Targets: 87

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: TNFRSF25/DR3/APO3/LARD/TRAMP/WSL1, - Tumor Necrosis Factor Receptor Superfamily Member 25 / Death Receptor 3
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

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