TET2 Cancer Research Results

TET2, tet oncogene family member 2: Click to Expand ⟱
Source: CGL-Driver Genes
Type: TSG
TET2 (Ten-Eleven Translocation 2) is a gene that encodes an enzyme involved in the process of DNA demethylation, which is crucial for regulating gene expression and maintaining genomic stability.
TET2 is a critical epigenetic regulator whose dysregulation—mainly through mutations—plays a significant role in the development and progression of various cancers, particularly in hematologic malignancies. Its impact on DNA methylation and subsequent gene expression changes makes it a key player in oncogenesis and a potential target for epigenetic therapies. The prognostic implications of TET2 mutations are context-dependent, contributing valuable information regarding disease progression, patient outcomes, and treatment response.

Loss-of-function mutations or reduced activity of TET2 can lead to aberrant DNA methylation patterns, which may result in inappropriate gene silencing (including of tumor suppressor genes) or activation of oncogenes. This disruption in the normal epigenetic landscape contributes to the development and progression of various cancers, particularly hematological malignancies such as myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML), and acute myeloid leukemia (AML).
Scientific Papers found: Click to Expand⟱
3435- aLinA,    Alpha-linolenic acid-mediated epigenetic reprogramming of cervical cancer cell lines
- in-vitro, Cerv, HeLa - in-vitro, Cerv, SiHa - in-vitro, Cerv, C33A
DNMTs↓, ALA increased DNA demethylase, HMTs, and HATs while decreasing global DNA methylation, DNMT, HDMs, and HDACs mRNA expression/activity in all cervical cancer cell lines.
HDAC↓,
HATs↑,
hTERT/TERT↓, ALA downregulated hTERT oncogene while upregulating the mRNA expression of TSGs (Tumor Suppressor Genes) CDH1, RARβ, and DAPK in all the cell lines.
CDH1↑,
RARβ↑,
DNMT1↓, In HeLa, ALA treatment reduced DNMT1 mRNA expression by 2.3-fold, 2.9-fold, and 3.3-fold at 20, 40, and 80 μM, respectively,
DNMT3A↓, ALA also reduced DNMT3B mRNA expression: in HeLa by 3.5-fold and 3.2-fold at 40 and 80 μM, i
TET2↑, ALA treatment induced TET2 mRNA expression, with an increase of 3.6-fold in HeLa at 80 μM.
HDAC1↓, ALA treatment in HeLa resulted in a significant reduction in HDAC1 mRNA expression, with decreases of 2.3-fold and 3.8-fold at 40 and 80 μM,
HDAC8↓, Treatment with ALA at 80 μM also led to reductions in HDAC8 mRNA expression by 2.4-fold, 2.0-fold, and 2.0-fold in HeLa, SiHa, and C33A, respectively.
SIRT1↓, ALA additionally decreased SIRT1 mRNA expression in HeLa by 2.4-fold and 2.5-fold at 40 and 80 μM, respectively.
HMTs↑,
EZH2↓, In HeLa, ALA treatment decreased EZH2 mRNA expression by 2.9-fold, 4.2-fold, and 4.2-fold at 20, 40, and 80 µM, respectively.

3426- TQ,    Thymoquinone-Induced Reactivation of Tumor Suppressor Genes in Cancer Cells Involves Epigenetic Mechanisms
- in-vitro, BC, MDA-MB-468 - in-vitro, AML, JK
UHRF1↓, (UHRF1), DNMT1,3A,3B, G9A, HDAC1,4,9, KDM1B, and KMT2A,B,C,D,E, were downregulated in TQ-treated Jurkat cells
DNMT1↓,
DNMT3A↓,
DNMTs↓,
HDAC1↓,
HDAC4↓,
HDAC↓,
DLC1↑, several TSGs, such as DLC1, PPARG, ST7, FOXO6, TET2, CYP1B1, SALL4, and DDIT3, known to be epigenetically silenced in various tumors, including acute leukemia, were upregulated,
PPARγ↑,
FOXO↑,
TET2↑,
CYP1B1↑,
G9a↓, expression of UHRF1, DNMT1, G9a, and HDAC1 genes in both cancer cell (Jurkat cells and MDA-MB-468 cells) lines depends on the TQ dose

3427- TQ,    Chemopreventive and Anticancer Effects of Thymoquinone: Cellular and Molecular Targets
ROS⇅, It appears that the cellular and/or physiological context(s) determines whether TQ acts as a pro-oxidant or an anti-ox- idant in vivo
Fas↑, Figure 2, cell death
DR5↑,
TRAIL↑,
Casp3↑,
Casp8↑,
Casp9↑,
P53↑,
mTOR↓,
Bcl-2↓,
BID↓,
CXCR4↓,
JNK↑,
p38↑,
MAPK↑,
LC3II↑,
ATG7↑,
Beclin-1↑,
AMPK↑,
PPARγ↑, cell survival
eIF2α↓,
P70S6K↓,
VEGF↓,
ERK↓,
NF-kB↓,
XIAP↓,
survivin↓,
p65↓,
DLC1↑, epigenetic
FOXO↑,
TET2↑,
CYP1B1↑,
UHRF1↓,
DNMT1↓,
HDAC1↓,
IL2↑, inflammation
IL1↓,
IL6↓,
IL10↓,
IL12↓,
TNF-α↓,
iNOS↓,
COX2↓,
5LO↓,
AP-1↓,
PI3K↓, invastion
Akt↓,
cMET↓,
VEGFR2↓,
CXCL1↓,
ITGA5↓,
Wnt↓,
β-catenin/ZEB1↓,
GSK‐3β↓,
Myc↓,
cycD1/CCND1↓,
N-cadherin↓,
Snail↓,
Slug↓,
Vim↓,
Twist↓,
Zeb1↓,
MMP2↓,
MMP7↓,
MMP9↓,
JAK2↓, cell proliferiation
STAT3↓,
NOTCH↓,
cycA1/CCNA1↓,
CDK2↓,
CDK4↓,
CDK6↓,
CDC2↓,
CDC25↓,
Mcl-1↓,
E2Fs↓,
p16↑,
p27↑,
P21↑,
ChemoSen↑, Such chemo-potentiating effects of TQ in different cancer cells have been observed with 5-fluorouracil in gastric cancer and colorectal cancer models

632- VitC,    High-Dose Vitamin C: Preclinical Evidence for Tailoring Treatment in Cancer Patients
- Review, NA, NA
SVCT-2∅, vitamin C entry into cells is tightly regulated by SVCT
ROS↑, well-recognized pro-oxidant effects
Hif1a↓, HIF-1α proteasomal degradation
PARP∅, Moreover, vitamin C action at DNA levels may provide the rationale basis for combination therapies with PARP inhibitors and hypomethylating agents.
TET2↑, However, the ability of vitamin C to restore TET2 activity seems to depend on N- and C-terminal lysine acetylation and type of TET2 mutations

3142- VitC,    Vitamin C promotes apoptosis in breast cancer cells by increasing TRAIL expression
- in-vitro, BC, MDA-MB-231 - in-vitro, BC, MCF-7 - in-vitro, Nor, MCF12A
TET2↑, Vitamin C serves as a cofactor for TET methylcytosine dioxygenases to increase 5hmC generation.
Apoptosis↑, vitamin C treatment induced apoptosis in MDA-MB-231 cells, which was verified in two additional breast cancer cell lines.
TRAIL↑, Vitamin C upregulated TRAIL transcripts (2.3-fold increase) and increased TRAIL protein levels.
BAX↑, apoptosis promoted by vitamin C was associated with Bax and caspases activation, Bcl-xL sequestration, and cytochrome c release
Casp↑,
Cyt‑c↑,
HK2↓, downregulated genes (TFRC, PGK1, BNIP3, NDRG1, BNIP3L, ADM, PDK1, HK2)
PDK1↓,
BNIP3↓,

3148- VitC,    Antioxidants in brain tumors: current therapeutic significance and future prospects
- Review, Var, NA
*antiOx↑, At dietary concentrations, vitamin C exhibits an antioxidant mechanism and prevent tumorigenesis [74]. Vitamin C prevents DNA damage by reducing OS, thereby preventing carcinogenesis
*ROS↓,
chemoPv↑, Vitamin C exhibits both chemopreventive and chemotherapeutic roles via antioxidant and prooxidant mechanisms, respectively
ChemoSen↑,
TET2↑, activating ten-eleven translocation proteins (TETs)
eff↑, A regular supplement of vitamin C during pregnancy was found to reduce the risk of the fetus in developing pediatric brain tumors
OS↑, ascorbate demonstrated safety and chemotherapeutic efficacy in prolonging life span and improving quality of life
QoL↑,
eff↑, Vitamin C has been found to enhance the chemotherapeutic effects of methotrexate on glioblastoma cells

3120- VitC,    Upregulation of TET activity with ascorbic acid induces epigenetic modulation of lymphoma cells
- in-vitro, lymphoma, NA
TET2↑, ascorbic acid (AA) is a cofactor for TET with a binding site at the catalytic domain, and enhances TET activity
Smad1↑, AA treatment increased the expression of SMAD1, a tumor suppressor gene known to be suppressed by methylation, and increased chemosensitivity of lymphoma cells.
ChemoSen↑,
other↝, AA treatment produced a progressive decrease in DNA methylation and an increase in the hydroxymethylation fraction in a dose-dependent manner, correlating with the increase in TET activity

3113- VitC,    Vitamin C enhances NF-κB-driven epigenomic reprogramming and boosts the immunogenic properties of dendritic cells
- in-vitro, Nor, NA
TET2↑, intravenous vitamin C treatment in mice abrogates cancer progression through direct TET2 function restoration in cancer cells
NF-kB↑, Vitamin C triggers extensive demethylation at NF-κB/p65 binding sites

3114- VitC,    Restoration of TET2 Function Blocks Aberrant Self-Renewal and Leukemia Progression
- in-vitro, AML, NA
TET2↑, Treatment with vitamin C, a cofactor of Fe2+ and α-KG-dependent dioxygenases, mimics TET2 restoration by enhancing 5-hydroxymethylcytosine formation in Tet2-deficient mouse HSPCs
eff↑, enhances the efficacy of PARP inhibition in suppressing leukemia progression.
ROS↑, High levels of vitamin C can lead to reactive oxygen species (ROS) production via the Fenton reaction
Fenton↑,
Hif1a↓, One study suggested that vitamin C decreases viability of human leukemia cell lines by promoting downregulation of HIF1α and the anti-apoptotic genes, BCL2, BCL2L1, and MCL1

3118- VitC,    Vitamin C boosts DNA demethylation in TET2 germline mutation carriers
- Trial, Nor, NA
TET2↑, vitamin C reinforces the DNA demethylation cascade,

3119- VitC,    Ascorbic acid–induced TET activation mitigates adverse hydroxymethylcytosine loss in renal cell carcinoma
- in-vitro, RCC, NA
TET2↑, Ascorbic acid–induced TET activation
TumCG↓, Pharmacologic AA treatment led to reduced growth of ccRCC in vitro and reduced tumor growth in vivo, with increased intratumoral 5hmC.
tumCV↓, We observed acute loss in viability with high-dose AA that was reversed in the presence of catalase cotreatment, suggesting that the acute cytotoxicity with short-term exposure of high-dose AA (millimolar concentration) is primarily mediated by H2O2

3121- VitC,  immuno,    Ascorbic acid induced TET2 enzyme activation enhances cancer immunotherapy efficacy in renal cell carcinoma
- in-vivo, RCC, A498 - in-vitro, RCC, 786-O
TET2↑, Ascorbic acid induced TET2 enzyme activation enhances cancer immunotherapy efficacy in renal cell carcinoma
eff↑, Therefore, we speculated that restoring 5hmC levels in RCC promoting TET2 activity may have a synergistic effect with immune checkpoint therapy.
eff↑, Vitamin C sensitizes renal cell carcinoma to anti-PD-L1 treatment

3122- VitC,    Ascorbic Acid Promotes Plasma Cell Differentiation through Enhancing TET2/3-Mediated DNA Demethylation
TET2↑, ascorbic acid (vitamin C), an essential nutrient, is able to promote plasma cell differentiation and humoral immune response by enhancing TET2/3-mediated DNA demethylation
TET3↑,

3123- VitC,    Ascorbic Acid Enhances Tet-Mediated 5-Methylcytosine Oxidation and Promotes DNA Demethylation in Mammals
- in-vitro, Nor, mESC
*TET2↑, Here, we demonstrate that a vital nutrient ascorbic acid (AA), or vitamin C (Vc), can directly enhance the catalytic activity of Tet dioxygenases for the oxidation of 5-methylcytosine (5mC)
other↝, In mouse embryonic stem cells, AA significantly increases the levels of all 5mC oxidation products, particularly 5-formylcytosine and 5-carboxylcytosine (by more than an order of magnitude), leading to a global loss of 5mC (∼40%).

3124- VitC,    Ascorbic acid improves parthenogenetic embryo development through TET proteins in mice
- in-vivo, Nor, NA
TET2↑, Our results revealed that Vc stimulated the expression of TET proteins in PA embryos.
TET1↑,
TET3↑, present study suggest that up-regulated expression of TET proteins improves PA embryo development by increasing 5hmC levels.


Showing Research Papers: 1 to 15 of 15

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 15

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

Fenton↑, 1,   ROS↑, 2,   ROS⇅, 1,  

Mitochondria & Bioenergetics ⓘ

CDC2↓, 1,   CDC25↓, 1,   XIAP↓, 1,  

Core Metabolism/Glycolysis ⓘ

AMPK↑, 1,   ATG7↑, 1,   HK2↓, 1,   PDK1↓, 1,   PPARγ↑, 2,   RARβ↑, 1,   SIRT1↓, 1,  

Cell Death ⓘ

Akt↓, 1,   Apoptosis↑, 1,   BAX↑, 1,   Bcl-2↓, 1,   BID↓, 1,   Casp↑, 1,   Casp3↑, 1,   Casp8↑, 1,   Casp9↑, 1,   Cyt‑c↑, 1,   DR5↑, 1,   Fas↑, 1,   hTERT/TERT↓, 1,   iNOS↓, 1,   JNK↑, 1,   MAPK↑, 1,   Mcl-1↓, 1,   Myc↓, 1,   p27↑, 1,   p38↑, 1,   survivin↓, 1,   TRAIL↑, 2,  

Transcription & Epigenetics ⓘ

EZH2↓, 1,   HATs↑, 1,   other↝, 2,   TET3↑, 2,   tumCV↓, 1,  

Protein Folding & ER Stress ⓘ

eIF2α↓, 1,  

Autophagy & Lysosomes ⓘ

Beclin-1↑, 1,   BNIP3↓, 1,   LC3II↑, 1,  

DNA Damage & Repair ⓘ

CYP1B1↑, 2,   DNMT1↓, 3,   DNMT3A↓, 2,   DNMTs↓, 2,   G9a↓, 1,   p16↑, 1,   P53↑, 1,   PARP∅, 1,   UHRF1↓, 2,  

Cell Cycle & Senescence ⓘ

CDK2↓, 1,   CDK4↓, 1,   cycA1/CCNA1↓, 1,   cycD1/CCND1↓, 1,   E2Fs↓, 1,   P21↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

cMET↓, 1,   ERK↓, 1,   FOXO↑, 2,   GSK‐3β↓, 1,   HDAC↓, 2,   HDAC1↓, 3,   HDAC4↓, 1,   HDAC8↓, 1,   HMTs↑, 1,   mTOR↓, 1,   NOTCH↓, 1,   P70S6K↓, 1,   PI3K↓, 1,   STAT3↓, 1,   TumCG↓, 1,   Wnt↓, 1,  

Migration ⓘ

5LO↓, 1,   AP-1↓, 1,   CDH1↑, 1,   DLC1↑, 2,   ITGA5↓, 1,   MMP2↓, 1,   MMP7↓, 1,   MMP9↓, 1,   N-cadherin↓, 1,   Slug↓, 1,   Smad1↑, 1,   Snail↓, 1,   TET1↑, 1,   Twist↓, 1,   Vim↓, 1,   Zeb1↓, 1,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature ⓘ

Hif1a↓, 2,   VEGF↓, 1,   VEGFR2↓, 1,  

Barriers & Transport ⓘ

SVCT-2∅, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,   CXCL1↓, 1,   CXCR4↓, 1,   IL1↓, 1,   IL10↓, 1,   IL12↓, 1,   IL2↑, 1,   IL6↓, 1,   JAK2↓, 1,   NF-kB↓, 1,   NF-kB↑, 1,   p65↓, 1,   TNF-α↓, 1,  

Hormonal & Nuclear Receptors ⓘ

CDK6↓, 1,  

Drug Metabolism & Resistance ⓘ

ChemoSen↑, 3,   eff↑, 5,   TET2↑, 14,  

Clinical Biomarkers ⓘ

EZH2↓, 1,   hTERT/TERT↓, 1,   IL6↓, 1,   Myc↓, 1,  

Functional Outcomes ⓘ

chemoPv↑, 1,   OS↑, 1,   QoL↑, 1,  
Total Targets: 120

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 1,   ROS↓, 1,  

Drug Metabolism & Resistance ⓘ

TET2↑, 1,  
Total Targets: 3

Scientific Paper Hit Count for: TET2, tet oncogene family member 2
12 Vitamin C (Ascorbic Acid)
2 Thymoquinone
1 alpha Linolenic acid
1 immunotherapy
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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