ATF6 Cancer Research Results
ATF6, Activating Transcription Factor 6: Click to Expand ⟱
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| Type: protein |
ATF6 (Activating Transcription Factor 6) is a protein that plays a crucial role in the unfolded protein response (UPR), a cellular stress response pathway that is activated in response to endoplasmic reticulum (ER) stress.
High ATF6 expression is associated with poor prognosis, including shorter overall survival and increased risk of recurrence.
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Scientific Papers found: Click to Expand⟱
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in-vitro, |
BC, |
MCF-7 |
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in-vitro, |
BC, |
T47D |
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Bacteria↓, Nowadays, silver nanoparticles (AgNP) are widely used in the medical field mainly for their antibacterial properties
Apoptosis↑, AgNP of 2 (AgNP2) and 15 nm (AgNP15) induce apoptosis in human MCF-7 and T-47D breast cancer cells.
ER Stress↑, Treatment with AgNP2 and AgNP15 led to accumulation and aggregation of misfolded proteins causing an endoplasmic reticulum (ER) stress and activating the unfolded protein response (UPR).
UPR↑,
PERK↑, The three main ER sensors, PERK, IRE-1α and ATF-6, were rapidly activated in response to AgNP2 and AgNP15
IRE1↑,
ATF6↑,
ATF4↑, AgNP2 and AgNP15 induced upregulation of the transcription factors ATF-4 and GADD153/CHOP
CHOP↑,
Casp9↑, Moreover, the initiating caspase-9 and the effector caspase-7 were activated in response to these NPs.
Casp7↑,
Mcl-1↓, In contrast, a downregulation of Mcl-1 and xIAP protein expression as well as a processing of PARP were observed.
XIAP↓,
PARP↝,
selectivity↑, Of note, the non-cancerous MCF-10A cells were more resistant to both AgNP2 and AgNP15 when compared to MCF-7 and T-47D cell lines.
Apoptosis↑,
Ca+2↑, mitochondrial Ca(2+) overloading
ER Stress↑,
PERK↑, ER stress marker
IRE1↑, ER stress marker
cl‑ATF6↑, ATF6, ER stress marker
*ROS↑, Several studies have reported that AgNPs induce genotoxicity and cytotoxicity in both cancer and normal cell lines
Akt↓, high ROS levels, and reduced Akt and ERK signaling.
ERK↓,
DNAdam↑, increased ROS production, leading to oxidative DNA damage and apoptosis
Ca+2↑, The damage caused to the cell membrane is due to intracellular calcium overload, and further causes ROS overproduction and mitochondrial membrane potential variation
ROS↑,
MMP↓,
Cyt‑c↑, AgNPs induce apoptosis through release of cytochrome c into the cytosol and translocation of Bax to the mitochondria, and also cause cell cycle arrest in the G1 and S phases
TumCCA↑,
DNAdam↑, main result of AgNP toxicity is direct and oxidative DNA damage, ultimately causing apoptosis
Apoptosis↑,
P53↑, AgNPs induce apoptosis in spermatogonial stem cells through increased levels of ROS; mitochondrial dysfunction; upregulation of p53 expression; pErk1/2;
p‑ERK↑,
ER Stress↑, endoplasmic reticulum (ER) stress-induced apoptosis caused by AgNPs has attracted much research interest
cl‑ATF6↑, cleavage of activating transcription factor 6 (ATF6), and upregulation of glucose-regulated protein-78 and CCAAT/enhancer-binding protein-homologous protein (CHOP/GADD153)
GRP78/BiP↑,
CHOP↑,
UPR↑, In order to protect the cells against nanoparticle-mediated toxicity, the ER rapidly responds with the unfolded protein response (UPR), an important cellular self-protection mechanism
TumCP↓, Treatment of DU-145 prostate cancer cells with physiological concentrations of BA inhibits cell proliferation without causing apoptosis and activates eukaryotic initiation factor 2 (eIF2α).
eIF2α↑, Phosphorylation of eIF2α occurs following BA treatment of DU-145 and LNCaP prostate cells
ATF4↑, post-treatment increases in eIF2α protein at 30 min and ATF4 and ATF6 proteins at 1 h and 30 min, respectively
ATF6↑,
GADD34↑, The increase in ATF4 was accompanied by an increase in the expression of its downstream genes growth arrest and DNA damage-induced protein 34 (GADD34) and homocysteine-induced ER protein (Herp),
CHOP↓, but a decrease in GADD153/CCAAT/enhancer-binding protein homologous protein (CHOP), a pro-apoptotic gene.
GRP78/BiP↑, The increase in ATF6 was accompanied by an increase in expression of its downstream genes GRP78/BiP, calreticulin, Grp94, and EDEM.
GRP94↑,
Risk↓, Low boron status has been associated with increased cancer risk, low bone mineralization, and retinal degeneration
*BMD↑,
Ca+2↓, LNCaP and DU-145: BA binds to cADPR and inhibits cADPR-activated Ca2+ release from the endoplasmic reticulum (ER) in a dose-dependent manner [15, 16] and lowers ER luminal Ca2+ concentrations
*Half-Life↝, lood levels of BA are dynamic, rising rapidly after a meal with an elimination half-life from 4 to 27.8 h depending on dose
IRE1∅, BA does not activate IRE1
chemoP↑, Dietary boron has been connected to three seemingly unconnected observations, increased bone mass and strength [10, 74, 75], chemoprevention
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in-vitro, |
HCC, |
HepG2 |
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in-vitro, |
Nor, |
HL7702 |
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TumCCA↑, cell cycle arrest in the G1/G0 phase
SLC12A5↓,
ATF6↑,
CHOP↑,
GRP78/BiP↑,
Casp3↑,
ER Stress↝,
*toxicity↓, HL‐7702 cells(normal) treated with 22.6 and 45.7 mM borax for 24 h showed no notable abnormalities in cellular size and cytoplasmic volume compared to the control group
*eff↓, tumour blood vessels absorb much higher levels of boric acid than normal liver tissues
NAD↝, high affinity for the ribose moieties of NAD+
SAM-e↝, high affinity for S-adenosylmethione
PSA↓,
IGF-1↓,
Cyc↓, reduction in cyclins A–E
P21↓,
p‑MEK↓,
p‑ERK↓, ERK (P-ERK1/2)
ROS↑, induce oxidative stress by decreasing superoxide dismutase (SOD) and catalase (CAT)
SOD↓,
Catalase↓,
MDA↑,
GSH↓,
IL1↓, IL-1α
IL6↓,
TNF-α↓,
BRAF↝,
MAPK↝,
PTEN↝,
PI3K/Akt↝,
eIF2α↑,
ATF4↑,
ATF6↑,
NRF2↑,
BAX↑,
BID↑,
Casp3↑,
Casp9↑,
Bcl-2↓,
Bcl-xL↓,
DNAdam↑, It is generally agreed that DNA is the preferential and cytotoxic target for cisplatin and other platinating agents. able to induce similar numbers of single-strand and double-strand breaks on DNA
ER Stress↑, shown to cause activation of apoptotic caspases through activation of the endoplasmic reticulum (ER) stress pathway (
UPR↑, When the ER experiences stress such as starvation or treatment with inhibitors of N-glycosylation (e.g. tunicamycin), it cannot fold or transport proteins correctly, and the UPR is activated.
ATF4↑, regulatory components of the ER stress pathway, including ATF4, ATF6, XBP1, and BiP (Grp78), are upregulated
ATF6↑,
XBP-1↑,
GRP78/BiP↑,
NP/CIPN↝, Carboplatin is notably less neurotoxic than cisplatin at conventional doses, with a similar sensory neuropathy occurring in approximately 6% of patients
toxicity↝, Carboplatin rarely results in nephrotoxicity and peripheral neuropathy, with its major toxicity being myelosuppression
eff↑, exposure to buthiomine sulfoximine (BSO), which significantly depleted cellular glutathione concentration, resulted in a significant enhancement in cisplatin cytotoxicity [151].
TrxR1⇅, Both cisplatin and transplatin show this inhibition of TxrR1 [161], as does oxaliplatin but not carboplatin [162]
*antiOx↑, Curcumin is a plant polyphenol in turmeric root and a potent antioxidant
*NRF2↑, regulation by nuclear factor erythroid 2-related factor 2, thereby suppressing reactive oxygen species (ROS) and exerting anti-inflammatory, anti-infective and other pharmacological effects
*ROS↓,
*Inflam↓,
ROS↑, Of note, curcumin induces oxidative stress in tumors. curcumin-induced accumulation of ROS in tumors to kill tumor cells has been noted in several studies
p‑ERK↑, Curcumin promoted ERK/JNK phosphorylation, causing elevated ROS levels and triggering mitochondria-dependent apoptosis
ER Stress↑, Curcumin triggered disturbances in Ca2+ homeostasis, leading to endoplasmic reticulum stress, mitochondrial damage and apoptosis
mtDam↑,
Apoptosis↑,
Akt↓, Curcumin inhibited the AKT/mTOR/p70S6K signaling pathway
mTOR↓,
HO-1↑, Curcumin-induced HO-1 overexpression led to a disturbed intracellular iron distribution and triggered the Fenton reaction
Fenton↑,
GSH↓, Non-small cell lung cancer: Curcumin induced a decrease in GSH and an increase in ROS levels and iron accumulation
Iron↑,
p‑JNK↑, Curcumin causes mitochondrial damage by promoting phosphorylation of ERK and JNK, resulting in the increased release of ROS and cytochrome c into the cytoplasm, thereby triggering a mitochondrion-dependent pathway of apoptosis
Cyt‑c↑,
ATF6↑, thyroid cancer with curcumin, both activating transcription factor (ATF) 6 and the ER stress marker C/EBP homologous protein (CHOP) were activated by curcumin and Ca2+-ATPase activity was also affected.
CHOP↑,
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in-vitro, |
PC, |
PANC1 |
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in-vitro, |
PC, |
Bxpc-3 |
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in-vitro, |
Nor, |
hTERT-HPNE |
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in-vivo, |
NA, |
NA |
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AMPK↑, We found that the AMPK/mTOR signaling pathway was enhanced after fisetin treatment
mTOR↑,
UPR↑, RNA-seq analysis revealed that the unfolded protein response pathway, which is activated by ER stress, was enriched
ER Stress↑, Fisetin induced ER stress in pancreatic cancer cells
selectivity↑, results showed that fisetin was less cytotoxic to normal cells compared with pancreatic cancer cells
TumCP↓, fisetin inhibited the proliferation of PANC-1 cells
PERK↑, expression of PERK, ATF4, and ATF6 were also upregulated by fisetin
ATF4↑,
ATF6↑,
tumCV↓, GA treatment significantly reduced cell viabilities of NSCLC cells in a concentration-dependent manner.
ROS↑, GA treatment increased intracellular ROS level,
GRP78/BiP↑, expression levels of GRP (glucose-regulated protein) 78
CHOP↑, CHOP (C/EBP-homologous protein),
ATF6↑, ATF (activating transcription factor) 6 and caspase 12,
Casp12↑,
p‑PERK↑, phosphorylation levels of PERK
ER Stress↑, Induced Endoplasmic Reticulum (ER) Stress-Mediated Apoptosis
Apoptosis↑, Luteolin induced apoptotic cell death and activation of caspase-12, -9, and -3
TumCD↑,
Casp12↑,
Casp9↑,
Casp3↑,
ER Stress↑, Luteolin also induced expression of endoplasmic reticulum (ER) stress-associated proteins, including C/EBP homologous protein (CHOP) and glucose-regulated proteins (GRP) 94 and 78, cleavage of ATF6α, and phosphorylation of eIF2α
CHOP↑,
GRP78/BiP↑,
GRP94↑,
cl‑ATF6↑,
p‑eIF2α↑,
MMP↓, rapid reduction of mitochondrial membrane potential by luteolin
JNK↓, luteolin induced activation of mitogen-activated protein kinases such as JNK, p38, and ERK
p38↑,
ERK↑,
Cyt‑c↑, cytochrome c release.
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in-vitro, |
Ovarian, |
PA1 |
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in-vitro, |
Ovarian, |
SKOV3 |
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ROS↑, PEITC caused increased ROS-accumulation and inhibited proliferation selectively in ovarian cancer cells, and glutathione (GSH) depletion in SKOV-3.
TumCP↓,
GSH↓, One of the generating ROS mechanisms by PEITC is a depletion of GSH
selectivity↑, However, PEITC did not cause any effect in normal ovarian epithelial cells and peripheral blood mononuclear cells
UPR↑, PEITC Induces Unfolded Protein Response, Attenuated by NAC, in Ovarian Cancer Cells
CHOP↑, The key regulator of UPR-mediated apoptosis, CHOP/GADD153 and endoplasmic reticulum resident chaperone BiP/GRP78 were parallely up-regulated
ER Stress↑,
GRP78/BiP↑,
PERK↑, with activation of two major sensors of the UPR [PERK and ATF-6 in PA-1; PERK, and IRE1α in SKOV-3) in response to ROS accumulation induced by PEITC (5 μM)
ATF6↑,
eff↓, ROS scavenger, N-acetyl-L-cysteine (NAC), attenuated the effect of PEITC on UPR signatures (P-PERK, IRE1α, CHOP/GADD153, and BiP/GRP78)
TumCG↓, PEITC Inhibits Growth of Ovarian Cancer Cells without Inhibiting the Growth of Normal PBMC Cells
Apoptosis↑, PEITC Induces Apoptotic Cell Death in Ovarian Cancer Cell Lines
toxicity↓, IC50 value of PEITC for endothelial cells was more than 100 μM, suggesting cancer cell-specific cell death by PEITC (28). PEITC is a well-known ROS inducer in cancer cells without any potential adverse effect on normal cells (
Apoptosis↑, The apoptosis rate in the quercetin group increased significantly in comparison with the blank control group,
cycD1/CCND1↓, Cyclin D1 showed a tendency to decrease progressively
Casp3↑, Caspase-3, GRP78, and CHOP expression levels in the quercetin intervention group rose significantly in comparison with the blank control group
GRP78/BiP↑,
CHOP↑,
tumCV↓, viability of the cervical cancer HeLe cells was inhibited by quercetin in a dose-dependent manner
IRE1↑, The IRE1, p-Perk, and c-ATF6 levels in the quercetin intervention group (20, 40, and 80 μmol/L) rose gradually in comparison with the blank control group
p‑PERK↑,
c-ATF6↑,
ER Stress↑, quercetin can induce ERS to initiate HeLe cell apoptosis.
UPR↑, treatment with RES lead to the activation of all 3 branches of the UPR
IRE1↑, with early splicing of XBP-1 indicative of IRE1 activation, phosphorylation of eIF2α consistent with ER resident kinase (PERK) activation, activating transcription factor 6 (ATF6) splicing
p‑eIF2α↑,
PERK↑,
ATF6↑,
GRP78/BiP↑, increase in expression levels of the downstream molecules GRP78/BiP, GRP94 and CHOP/GADD153 in human Burkitt's lymphoma Raji and Daudi cell lines.
GRP94↑,
CHOP↑,
GADD34↑, RES induces a pathway initiated by phosphorylation of eIF2α and followed by the upregulation of GADD34 and ATF4.
ATF4↑,
XBP-1↑, RES increased XBP-1 expression both in Raji and in Daudi cells
Ca+2↑, RES was found to significantly increase cytosolic Ca2+
ER Stress↑, RES was able to induce ER stress and activated all 3 branches of the UPR.
GSK‐3β↑, resveratrol suppressed the hexosamine biosynthetic pathway and interrupted protein glycosylation through GSK3β activation
Akt↓, Akt attenuation in response to resveratrol.
CHOP↑, Resveratrol-mediated disruption of protein glycosylation induced cellular apoptosis as indicated by the up-regulation of GADD153, followed by the activation of ER-stress sensors (PERK and ATF6α).
ER Stress↑,
PERK↑,
ATF6↑,
UPR↑, Disruption of protein glycosylation causes the accumulation of aberrant of proteins in the endoplasmic reticulum (ER) which in turn activates unfolded protein responses (UPR) in the ER, leading to severe stressful conditions
GlucoseCon↓, Previous studies have shown that resveratrol (RSV) impairs glucose consumption via Akt/GLUT1 axis in cancer [
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in-vitro, |
Bladder, |
T24/HTB-9 |
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in-vitro, |
Bladder, |
253J |
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in-vitro, |
Nor, |
SV-HUC-1 |
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TumCP↓, TQ has a significant cytotoxicity on bladder cancer cells and can inhibit their proliferation and induce apoptosis.
Apoptosis↑,
ER Stress↑, The protein changes of Bcl-2, Bax, cytochrome c and endoplasmic reticulum stress-related proteins (GRP78, CHOP, and caspase-12) revealed that the anticancer effect of TQ was associated with mitochondrial dysfunction and the endoplasmic reticulum stre
cl‑Casp3↑, TQ increased the cleaved subunits of caspase-3, caspase-8, caspase-7 and PARP (Fig. 2B) and increased caspase-3 activity (Fig. 2C) in a dose-dependent manner.
cl‑Casp8↑,
cl‑Casp7↑,
cl‑PARP↑,
Cyt‑c↑, can increase the release of cytochrome c
PERK↑, TQ increased the expression of PERK, IRE1 and ATF6 and the expression of downstream molecules such as p-eIF2a and ATF4 in a dose-dependent manner
IRE1↑,
ATF6↑,
p‑eIF2α↑,
ATF4↑,
GRP78/BiP↑, GRP78, IRE1, ATF6, ATF4 and CHOP was significantly increased after TQ treatment
CHOP↑,
Showing Research Papers: 1 to 16 of 16
* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 16
Pathway results for Effect on Cancer / Diseased Cells:
Redox & Oxidative Stress ⓘ
Catalase↓, 1, Fenton↑, 1, GSH↓, 3, HO-1↑, 1, Iron↑, 1, MDA↑, 1, NRF2↑, 1, ROS↑, 5, SAM-e↝, 1, SOD↓, 1, TrxR1⇅, 1,
Mitochondria & Bioenergetics ⓘ
p‑MEK↓, 1, MMP↓, 2, mtDam↑, 1, XIAP↓, 1,
Core Metabolism/Glycolysis ⓘ
AMPK↑, 1, GlucoseCon↓, 1, NAD↝, 1, PI3K/Akt↝, 1,
Cell Death ⓘ
Akt↓, 3, Apoptosis↑, 8, BAX↑, 1, Bcl-2↓, 1, Bcl-xL↓, 1, BID↑, 1, Casp12↑, 2, Casp3↑, 4, cl‑Casp3↑, 1, Casp7↑, 1, cl‑Casp7↑, 1, cl‑Casp8↑, 1, Casp9↑, 3, Cyt‑c↑, 4, GADD34↑, 2, JNK↓, 1, p‑JNK↑, 1, MAPK↝, 1, Mcl-1↓, 1, p38↑, 1, TumCD↑, 1,
Transcription & Epigenetics ⓘ
tumCV↓, 2,
Protein Folding & ER Stress ⓘ
ATF6↑, 12, cl‑ATF6↑, 3, c-ATF6↑, 1, CHOP↓, 1, CHOP↑, 11, eIF2α↑, 2, p‑eIF2α↑, 3, ER Stress↑, 13, ER Stress↝, 1, GRP78/BiP↑, 10, GRP94↑, 3, IRE1↑, 5, IRE1∅, 1, PERK↑, 7, p‑PERK↑, 2, UPR↑, 7, XBP-1↑, 2,
DNA Damage & Repair ⓘ
DNAdam↑, 3, P53↑, 1, PARP↝, 1, cl‑PARP↑, 1,
Cell Cycle & Senescence ⓘ
Cyc↓, 1, cycD1/CCND1↓, 1, P21↓, 1, TumCCA↑, 2,
Proliferation, Differentiation & Cell State ⓘ
BRAF↝, 1, ERK↓, 1, ERK↑, 1, p‑ERK↓, 1, p‑ERK↑, 2, GSK‐3β↑, 1, IGF-1↓, 1, mTOR↓, 1, mTOR↑, 1, PTEN↝, 1, TumCG↓, 1,
Migration ⓘ
Ca+2↓, 1, Ca+2↑, 3, TumCP↓, 4,
Angiogenesis & Vasculature ⓘ
ATF4↑, 7,
Barriers & Transport ⓘ
SLC12A5↓, 1,
Immune & Inflammatory Signaling ⓘ
IL1↓, 1, IL6↓, 1, PSA↓, 1, TNF-α↓, 1,
Drug Metabolism & Resistance ⓘ
eff↓, 1, eff↑, 1, selectivity↑, 3,
Clinical Biomarkers ⓘ
BRAF↝, 1, IL6↓, 1, PSA↓, 1,
Functional Outcomes ⓘ
chemoP↑, 1, NP/CIPN↝, 1, Risk↓, 1, toxicity↓, 1, toxicity↝, 1,
Infection & Microbiome ⓘ
Bacteria↓, 1,
Total Targets: 98
Pathway results for Effect on Normal Cells:
Redox & Oxidative Stress ⓘ
antiOx↑, 1, NRF2↑, 1, ROS↓, 1, ROS↑, 1,
Immune & Inflammatory Signaling ⓘ
Inflam↓, 1,
Drug Metabolism & Resistance ⓘ
eff↓, 1, Half-Life↝, 1,
Clinical Biomarkers ⓘ
BMD↑, 1,
Functional Outcomes ⓘ
toxicity↓, 1,
Total Targets: 9
Scientific Paper Hit Count for: ATF6, Activating Transcription Factor 6
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#:861 State#:% Dir#:2
wNotes=on sortOrder:rid,rpid
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