m6A Target Gene Information

General Information of the m6A Target Gene (ID: M6ATAR00484)
Target Name Cystine/glutamate transporter (SLC7A11)
Synonyms
Amino acid transport system xc-; Calcium channel blocker resistance protein CCBR1; Solute carrier family 7 member 11; xCT
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Gene Name SLC7A11
Family amino acid-polyamine-organocation (APC) superfamily. L-type amino acid transporter (LAT) (TC 2.A.3.8) family. {ECO:0000305}.
Function
Sodium-independent, high-affinity exchange of anionic amino acids with high specificity for anionic form of cystine and glutamate. {ECO:0000269|PubMed:15151999}.
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Gene ID 55083
Uniprot ID
XCT_HUMAN
HGNC ID
HGNC:11059
Ensembl Gene ID
ENSG00000151012
KEGG ID
hsa:23657
Full List of m6A Methylation Regulator of This Target Gene and Corresponding Disease/Drug Response(s)
SLC7A11 can be regulated by the following regulator(s), and cause disease/drug response(s). You can browse detail information of regulator(s) or disease/drug response(s).
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Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) [READER]
 Regulator Info 
Representative RNA-seq result indicating the expression of this target gene regulated by IGF2BP1
Cell Line MV3 cell line Homo sapiens
Treatment: siIGF2BP1 MV3 cells
Control: siControl MV3 cells
 GSE146803
Regulation
logFC: -1.30E+00
p-value: 3.62E-06
More Results Click to View More RNA-seq Results
In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [1]
Response Summary METTL3-mediated Cystine/glutamate transporter (SLC7A11) m6A modification enhances hepatoblastoma ferroptosis resistance. The METTL3/IGF2BP1/m6A modification promotes SLC7A11 mRNA stability and upregulates its expression by inhibiting the deadenylation process.
Target Regulation Up regulation
Responsed Disease Hepatoblastoma ICD-11: 2C12.01
 Disease Info 
Pathway Response Ferroptosis hsa04216
Cell Process Ferroptosis
In-vitro Model HuH-6 Hepatoblastoma Homo sapiens CVCL_4381
Hep-G2 Hepatoblastoma Homo sapiens CVCL_0027
HEK293T Normal Homo sapiens CVCL_0063
Methyltransferase-like 14 (METTL14) [WRITER]
 Regulator Info 
Representative RNA-seq result indicating the expression of this target gene regulated by METTL14
Cell Line HepG2 cell line Homo sapiens
Treatment: shMETTL14 HepG2 cells
Control: shCtrl HepG2 cells
 GSE121949
Regulation
logFC: -1.11E+00
p-value: 3.96E-11
More Results Click to View More RNA-seq Results
In total 4 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [2]
Response Summary METTL14 induced m6A modification at 5'UTR of Cystine/glutamate transporter (SLC7A11) mRNA, which in turn underwent degradation relied on the YTHDF2-dependent pathway. Identify the HIF-1alpha /METTL14/YTHDF2/SLC7A11 axis as a potential therapeutic target for the HCC interventional embolization treatment.
Target Regulation Down regulation
Responsed Disease Liver cancer ICD-11: 2C12
 Disease Info 
Pathway Response HIF-1 signaling pathway hsa04066
Cell Process RNA stability
In-vitro Model PLC/PRF/5 Adult hepatocellular carcinoma Homo sapiens CVCL_0485
MHCC97-H Adult hepatocellular carcinoma Homo sapiens CVCL_4972
L-02 Endocervical adenocarcinoma Homo sapiens CVCL_6926
Huh-7 Adult hepatocellular carcinoma Homo sapiens CVCL_0336
Hep-G2 Hepatoblastoma Homo sapiens CVCL_0027
HCCLM3 Adult hepatocellular carcinoma Homo sapiens CVCL_6832
BEL-7402 Endocervical adenocarcinoma Homo sapiens CVCL_5492
7721 (Human hepatic malignant cell line)
In-vivo Model For the subcutaneous implantation model, 5 × 105 stable SLC7A11-knockdown HCCLM3 cells or SLC7A11-vector cells were injected subcutaneously into BALB/C nude mice.
Experiment 2 Reporting the m6A Methylation Regulator of This Target Gene [3]
Response Summary m6A-hypomethylation regulated FGFR4 phosphorylates GSK-3beta and activates beta-catenin/TCF4-Cystine/glutamate transporter (SLC7A11)/FPN1 signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer.
Target Regulation Down regulation
Responsed Disease Breast cancer ICD-11: 2C60
 Disease Info 
Responsed Drug Pertuzumab Approved
 Drug Info 
Pathway Response Wnt signaling pathway hsa04310
Cell Process Glutathione synthesis
In-vitro Model ZR-75-1 Invasive breast carcinoma Homo sapiens CVCL_0588
T-47D Invasive breast carcinoma Homo sapiens CVCL_0553
SUM-159 (A mesenchymal triple-negative breast cancer cell line)
SK-BR-3 Breast adenocarcinoma Homo sapiens CVCL_0033
MDA-MB-468 Breast adenocarcinoma Homo sapiens CVCL_0419
MDA-MB-453 Breast adenocarcinoma Homo sapiens CVCL_0418
MDA-MB-361 Breast adenocarcinoma Homo sapiens CVCL_0620
MDA-MB-231 Breast adenocarcinoma Homo sapiens CVCL_0062
MCF-7 Invasive breast carcinoma Homo sapiens CVCL_0031
MCF-10A Normal Homo sapiens CVCL_0598
HEK293T Normal Homo sapiens CVCL_0063
BT-549 Invasive breast carcinoma Homo sapiens CVCL_1092
BT-474 Invasive breast carcinoma Homo sapiens CVCL_0179
AU565 Breast adenocarcinoma Homo sapiens CVCL_1074
In-vivo Model Luciferase-labeled rSKBR3 and MDA-MB-361 cells (1 × 107 cells) mixed with 1:1 Matrigel (Corning, 356237) were subcutaneously injected into the fat pads of mice. After a tumor was palpable, the mice were randomized into four groups (five mice per group), and they were treated with vehicle, trastuzumab (20 mg/kg, intraperitoneal administration), roblitinib (30 mg/kg, oral administration), or a combination of both drugs.
Experiment 3 Reporting the m6A Methylation Regulator of This Target Gene [3]
Response Summary m6A-hypomethylation regulated FGFR4 phosphorylates GSK-3beta and activates beta-catenin/TCF4-Cystine/glutamate transporter (SLC7A11)/FPN1 signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer.
Target Regulation Down regulation
Responsed Disease Breast cancer ICD-11: 2C60
 Disease Info 
Responsed Drug Trastuzumab Approved
 Drug Info 
Pathway Response Wnt signaling pathway hsa04310
Cell Process Glutathione synthesis
In-vitro Model ZR-75-1 Invasive breast carcinoma Homo sapiens CVCL_0588
T-47D Invasive breast carcinoma Homo sapiens CVCL_0553
SUM-159 (A mesenchymal triple-negative breast cancer cell line)
SK-BR-3 Breast adenocarcinoma Homo sapiens CVCL_0033
MDA-MB-468 Breast adenocarcinoma Homo sapiens CVCL_0419
MDA-MB-453 Breast adenocarcinoma Homo sapiens CVCL_0418
MDA-MB-361 Breast adenocarcinoma Homo sapiens CVCL_0620
MDA-MB-231 Breast adenocarcinoma Homo sapiens CVCL_0062
MCF-7 Invasive breast carcinoma Homo sapiens CVCL_0031
MCF-10A Normal Homo sapiens CVCL_0598
HEK293T Normal Homo sapiens CVCL_0063
BT-549 Invasive breast carcinoma Homo sapiens CVCL_1092
BT-474 Invasive breast carcinoma Homo sapiens CVCL_0179
AU565 Breast adenocarcinoma Homo sapiens CVCL_1074
In-vivo Model Luciferase-labeled rSKBR3 and MDA-MB-361 cells (1 × 107 cells) mixed with 1:1 Matrigel (Corning, 356237) were subcutaneously injected into the fat pads of mice. After a tumor was palpable, the mice were randomized into four groups (five mice per group), and they were treated with vehicle, trastuzumab (20 mg/kg, intraperitoneal administration), roblitinib (30 mg/kg, oral administration), or a combination of both drugs.
Experiment 4 Reporting the m6A Methylation Regulator of This Target Gene [3]
Response Summary m6A-hypomethylation regulated FGFR4 phosphorylates GSK-3beta and activates beta-catenin/TCF4-Cystine/glutamate transporter (SLC7A11)/FPN1 signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer.
Target Regulation Down regulation
Responsed Disease Breast cancer ICD-11: 2C60
 Disease Info 
Responsed Drug Tucatinib Approved
 Drug Info 
Pathway Response Wnt signaling pathway hsa04310
Cell Process Glutathione synthesis
In-vitro Model ZR-75-1 Invasive breast carcinoma Homo sapiens CVCL_0588
T-47D Invasive breast carcinoma Homo sapiens CVCL_0553
SUM-159 (A mesenchymal triple-negative breast cancer cell line)
SK-BR-3 Breast adenocarcinoma Homo sapiens CVCL_0033
MDA-MB-468 Breast adenocarcinoma Homo sapiens CVCL_0419
MDA-MB-453 Breast adenocarcinoma Homo sapiens CVCL_0418
MDA-MB-361 Breast adenocarcinoma Homo sapiens CVCL_0620
MDA-MB-231 Breast adenocarcinoma Homo sapiens CVCL_0062
MCF-7 Invasive breast carcinoma Homo sapiens CVCL_0031
MCF-10A Normal Homo sapiens CVCL_0598
HEK293T Normal Homo sapiens CVCL_0063
BT-549 Invasive breast carcinoma Homo sapiens CVCL_1092
BT-474 Invasive breast carcinoma Homo sapiens CVCL_0179
AU565 Breast adenocarcinoma Homo sapiens CVCL_1074
In-vivo Model Luciferase-labeled rSKBR3 and MDA-MB-361 cells (1 × 107 cells) mixed with 1:1 Matrigel (Corning, 356237) were subcutaneously injected into the fat pads of mice. After a tumor was palpable, the mice were randomized into four groups (five mice per group), and they were treated with vehicle, trastuzumab (20 mg/kg, intraperitoneal administration), roblitinib (30 mg/kg, oral administration), or a combination of both drugs.
Methyltransferase-like 3 (METTL3) [WRITER]
 Regulator Info 
Representative RNA-seq result indicating the expression of this target gene regulated by METTL3
Cell Line MOLM-13 cell line Homo sapiens
Treatment: shMETTL3 MOLM13 cells
Control: MOLM13 cells
 GSE98623
Regulation
logFC: -4.02E+00
p-value: 2.26E-108
More Results Click to View More RNA-seq Results
In total 2 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [1]
Response Summary METTL3-mediated Cystine/glutamate transporter (SLC7A11) m6A modification enhances hepatoblastoma ferroptosis resistance. The METTL3/IGF2BP1/m6A modification promotes SLC7A11 mRNA stability and upregulates its expression by inhibiting the deadenylation process.
Target Regulation Up regulation
Responsed Disease Hepatoblastoma ICD-11: 2C12.01
 Disease Info 
Pathway Response Ferroptosis hsa04216
Cell Process Ferroptosis
In-vitro Model HuH-6 Hepatoblastoma Homo sapiens CVCL_4381
Hep-G2 Hepatoblastoma Homo sapiens CVCL_0027
HEK293T Normal Homo sapiens CVCL_0063
Experiment 2 Reporting the m6A Methylation Regulator of This Target Gene [4]
Response Summary METTL3-mediated m-6A modification could stabilize Cystine/glutamate transporter (SLC7A11) mRNA and promote its translation, thus promoting LUAD cell proliferation and inhibiting cell ferroptosis, a novel form of programmed cell death.
Target Regulation Up regulation
Responsed Disease Lung adenocarcinoma ICD-11: 2C25.0
 Disease Info 
Pathway Response Ferroptosis hsa04216
Cell Process Ferroptosis
In-vitro Model SPC-A1 Endocervical adenocarcinoma Homo sapiens CVCL_6955
PC-9 Lung adenocarcinoma Homo sapiens CVCL_B260
NCI-H460 Lung large cell carcinoma Homo sapiens CVCL_0459
NCI-H322 Minimally invasive lung adenocarcinoma Homo sapiens CVCL_1556
NCI-H1975 Lung adenocarcinoma Homo sapiens CVCL_1511
NCI-H1299 Lung large cell carcinoma Homo sapiens CVCL_0060
BEAS-2B Normal Homo sapiens CVCL_0168
A-549 Lung adenocarcinoma Homo sapiens CVCL_0023
In-vivo Model For the subcutaneous xenograft model, PC9 cells stably transfected with METTL3 knockdown (shMETTL3) or negative control (shNC) shRNA (5 × 106 cells per mouse, n = 6) were suspended in 200 uL PBS with 50% Matrigel matrix (Corning, USA, 354234) and then injected into one side of the axilla of nude mice.
NF-kappa-B-activating protein (NKAP) [READER]
 Regulator Info 
In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [5]
Response Summary This study NKAP knockdown induced cell death in glioblastoma cells. NKAP acted as a new ferroptosis suppressor by binding to m6A and then promoting Cystine/glutamate transporter (SLC7A11) mRNA splicing and maturation.
Target Regulation Up regulation
Responsed Disease Glioblastoma ICD-11: 2A00.00
 Disease Info 
Pathway Response Ferroptosis hsa04216
Cell Process Ferroptosis
In-vitro Model U87MG (Astroblastoma cells from human brain)
U251 (Fibroblasts or fibroblast like cells)
In-vivo Model The male BALB/c nude mice were randomized divide into two groups, each group including six 4 weeks old nude mice. Investigators were blinded to the treatment groups during data collection and subsequent data analysis. In the subcutaneous xenograft model, 5 × 105 cells were subcutaneously injected in the right flanks of nude mice. In the orthotopic intracranial mouse model, each mouse was intracranially injected with 1 × 105 luciferase transfected U87MG cells in 10 uL PBS solution.
YTH domain-containing protein 2 (YTHDC2) [READER]
 Regulator Info 
In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [6]
Response Summary YTHDC2 destabilized Cystine/glutamate transporter (SLC7A11) mRNA in an m6A-dependent manner because YTHDC2 preferentially bound to m6A-modified SLC7A11 mRNA and thereafter promoted its decay. the promotion of cystine uptake via the suppression of YTHDC2 is critical for LUAD tumorigenesis
Target Regulation Down regulation
Responsed Disease Lung adenocarcinoma ICD-11: 2C25.0
 Disease Info 
In-vitro Model PC-9 Lung adenocarcinoma Homo sapiens CVCL_B260
NCI-H441 Lung papillary adenocarcinoma Homo sapiens CVCL_1561
NCI-H292 Lung mucoepidermoid carcinoma Homo sapiens CVCL_0455
NCI-H1975 Lung adenocarcinoma Homo sapiens CVCL_1511
NCI-H1650 Minimally invasive lung adenocarcinoma Homo sapiens CVCL_1483
NCI-H1299 Lung large cell carcinoma Homo sapiens CVCL_0060
HEK293T Normal Homo sapiens CVCL_0063
HCC827 Lung adenocarcinoma Homo sapiens CVCL_2063
Calu-1 Lung squamous cell carcinoma Homo sapiens CVCL_0608
BEAS-2B Normal Homo sapiens CVCL_0168
A-549 Lung adenocarcinoma Homo sapiens CVCL_0023
Brain cancer [ICD-11: 2A00]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [5]
Response Summary This study NKAP knockdown induced cell death in glioblastoma cells. NKAP acted as a new ferroptosis suppressor by binding to m6A and then promoting Cystine/glutamate transporter (SLC7A11) mRNA splicing and maturation.
Responsed Disease Glioblastoma [ICD-11: 2A00.00]
Target Regulator NF-kappa-B-activating protein (NKAP) READER
 Regulator Info 
Target Regulation Up regulation
Pathway Response Ferroptosis hsa04216
Cell Process Ferroptosis
In-vitro Model U87MG (Astroblastoma cells from human brain)
U251 (Fibroblasts or fibroblast like cells)
In-vivo Model The male BALB/c nude mice were randomized divide into two groups, each group including six 4 weeks old nude mice. Investigators were blinded to the treatment groups during data collection and subsequent data analysis. In the subcutaneous xenograft model, 5 × 105 cells were subcutaneously injected in the right flanks of nude mice. In the orthotopic intracranial mouse model, each mouse was intracranially injected with 1 × 105 luciferase transfected U87MG cells in 10 uL PBS solution.
Liver cancer [ICD-11: 2C12]
 Disease Info 
In total 3 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [1]
Response Summary METTL3-mediated Cystine/glutamate transporter (SLC7A11) m6A modification enhances hepatoblastoma ferroptosis resistance. The METTL3/IGF2BP1/m6A modification promotes SLC7A11 mRNA stability and upregulates its expression by inhibiting the deadenylation process.
Responsed Disease Hepatoblastoma [ICD-11: 2C12.01]
Target Regulator Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) READER
 Regulator Info 
Target Regulation Up regulation
Pathway Response Ferroptosis hsa04216
Cell Process Ferroptosis
In-vitro Model HuH-6 Hepatoblastoma Homo sapiens CVCL_4381
Hep-G2 Hepatoblastoma Homo sapiens CVCL_0027
HEK293T Normal Homo sapiens CVCL_0063
Experiment 2 Reporting the m6A-centered Disease Response [2]
Response Summary METTL14 induced m6A modification at 5'UTR of Cystine/glutamate transporter (SLC7A11) mRNA, which in turn underwent degradation relied on the YTHDF2-dependent pathway. Identify the HIF-1alpha /METTL14/YTHDF2/SLC7A11 axis as a potential therapeutic target for the HCC interventional embolization treatment.
Responsed Disease Liver cancer [ICD-11: 2C12]
Target Regulator Methyltransferase-like 14 (METTL14) WRITER
 Regulator Info 
Target Regulation Down regulation
Pathway Response HIF-1 signaling pathway hsa04066
Cell Process RNA stability
In-vitro Model PLC/PRF/5 Adult hepatocellular carcinoma Homo sapiens CVCL_0485
MHCC97-H Adult hepatocellular carcinoma Homo sapiens CVCL_4972
L-02 Endocervical adenocarcinoma Homo sapiens CVCL_6926
Huh-7 Adult hepatocellular carcinoma Homo sapiens CVCL_0336
Hep-G2 Hepatoblastoma Homo sapiens CVCL_0027
HCCLM3 Adult hepatocellular carcinoma Homo sapiens CVCL_6832
BEL-7402 Endocervical adenocarcinoma Homo sapiens CVCL_5492
7721 (Human hepatic malignant cell line)
In-vivo Model For the subcutaneous implantation model, 5 × 105 stable SLC7A11-knockdown HCCLM3 cells or SLC7A11-vector cells were injected subcutaneously into BALB/C nude mice.
Experiment 3 Reporting the m6A-centered Disease Response [1]
Response Summary METTL3-mediated Cystine/glutamate transporter (SLC7A11) m6A modification enhances hepatoblastoma ferroptosis resistance. The METTL3/IGF2BP1/m6A modification promotes SLC7A11 mRNA stability and upregulates its expression by inhibiting the deadenylation process.
Responsed Disease Hepatoblastoma [ICD-11: 2C12.01]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Up regulation
Pathway Response Ferroptosis hsa04216
Cell Process Ferroptosis
In-vitro Model HuH-6 Hepatoblastoma Homo sapiens CVCL_4381
Hep-G2 Hepatoblastoma Homo sapiens CVCL_0027
HEK293T Normal Homo sapiens CVCL_0063
Lung cancer [ICD-11: 2C25]
 Disease Info 
In total 2 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [4]
Response Summary METTL3-mediated m-6A modification could stabilize Cystine/glutamate transporter (SLC7A11) mRNA and promote its translation, thus promoting LUAD cell proliferation and inhibiting cell ferroptosis, a novel form of programmed cell death.
Responsed Disease Lung adenocarcinoma [ICD-11: 2C25.0]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Up regulation
Pathway Response Ferroptosis hsa04216
Cell Process Ferroptosis
In-vitro Model SPC-A1 Endocervical adenocarcinoma Homo sapiens CVCL_6955
PC-9 Lung adenocarcinoma Homo sapiens CVCL_B260
NCI-H460 Lung large cell carcinoma Homo sapiens CVCL_0459
NCI-H322 Minimally invasive lung adenocarcinoma Homo sapiens CVCL_1556
NCI-H1975 Lung adenocarcinoma Homo sapiens CVCL_1511
NCI-H1299 Lung large cell carcinoma Homo sapiens CVCL_0060
BEAS-2B Normal Homo sapiens CVCL_0168
A-549 Lung adenocarcinoma Homo sapiens CVCL_0023
In-vivo Model For the subcutaneous xenograft model, PC9 cells stably transfected with METTL3 knockdown (shMETTL3) or negative control (shNC) shRNA (5 × 106 cells per mouse, n = 6) were suspended in 200 uL PBS with 50% Matrigel matrix (Corning, USA, 354234) and then injected into one side of the axilla of nude mice.
Experiment 2 Reporting the m6A-centered Disease Response [6]
Response Summary YTHDC2 destabilized Cystine/glutamate transporter (SLC7A11) mRNA in an m6A-dependent manner because YTHDC2 preferentially bound to m6A-modified SLC7A11 mRNA and thereafter promoted its decay. the promotion of cystine uptake via the suppression of YTHDC2 is critical for LUAD tumorigenesis
Responsed Disease Lung adenocarcinoma [ICD-11: 2C25.0]
Target Regulator YTH domain-containing protein 2 (YTHDC2) READER
 Regulator Info 
Target Regulation Down regulation
In-vitro Model PC-9 Lung adenocarcinoma Homo sapiens CVCL_B260
NCI-H441 Lung papillary adenocarcinoma Homo sapiens CVCL_1561
NCI-H292 Lung mucoepidermoid carcinoma Homo sapiens CVCL_0455
NCI-H1975 Lung adenocarcinoma Homo sapiens CVCL_1511
NCI-H1650 Minimally invasive lung adenocarcinoma Homo sapiens CVCL_1483
NCI-H1299 Lung large cell carcinoma Homo sapiens CVCL_0060
HEK293T Normal Homo sapiens CVCL_0063
HCC827 Lung adenocarcinoma Homo sapiens CVCL_2063
Calu-1 Lung squamous cell carcinoma Homo sapiens CVCL_0608
BEAS-2B Normal Homo sapiens CVCL_0168
A-549 Lung adenocarcinoma Homo sapiens CVCL_0023
Breast cancer [ICD-11: 2C60]
 Disease Info 
In total 3 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [3]
Response Summary m6A-hypomethylation regulated FGFR4 phosphorylates GSK-3beta and activates beta-catenin/TCF4-Cystine/glutamate transporter (SLC7A11)/FPN1 signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer.
Responsed Disease Breast cancer [ICD-11: 2C60]
Target Regulator Methyltransferase-like 14 (METTL14) WRITER
 Regulator Info 
Target Regulation Down regulation
Responsed Drug Pertuzumab Approved
 Drug Info 
Pathway Response Wnt signaling pathway hsa04310
Cell Process Glutathione synthesis
In-vitro Model ZR-75-1 Invasive breast carcinoma Homo sapiens CVCL_0588
T-47D Invasive breast carcinoma Homo sapiens CVCL_0553
SUM-159 (A mesenchymal triple-negative breast cancer cell line)
SK-BR-3 Breast adenocarcinoma Homo sapiens CVCL_0033
MDA-MB-468 Breast adenocarcinoma Homo sapiens CVCL_0419
MDA-MB-453 Breast adenocarcinoma Homo sapiens CVCL_0418
MDA-MB-361 Breast adenocarcinoma Homo sapiens CVCL_0620
MDA-MB-231 Breast adenocarcinoma Homo sapiens CVCL_0062
MCF-7 Invasive breast carcinoma Homo sapiens CVCL_0031
MCF-10A Normal Homo sapiens CVCL_0598
HEK293T Normal Homo sapiens CVCL_0063
BT-549 Invasive breast carcinoma Homo sapiens CVCL_1092
BT-474 Invasive breast carcinoma Homo sapiens CVCL_0179
AU565 Breast adenocarcinoma Homo sapiens CVCL_1074
In-vivo Model Luciferase-labeled rSKBR3 and MDA-MB-361 cells (1 × 107 cells) mixed with 1:1 Matrigel (Corning, 356237) were subcutaneously injected into the fat pads of mice. After a tumor was palpable, the mice were randomized into four groups (five mice per group), and they were treated with vehicle, trastuzumab (20 mg/kg, intraperitoneal administration), roblitinib (30 mg/kg, oral administration), or a combination of both drugs.
Experiment 2 Reporting the m6A-centered Disease Response [3]
Response Summary m6A-hypomethylation regulated FGFR4 phosphorylates GSK-3beta and activates beta-catenin/TCF4-Cystine/glutamate transporter (SLC7A11)/FPN1 signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer.
Responsed Disease Breast cancer [ICD-11: 2C60]
Target Regulator Methyltransferase-like 14 (METTL14) WRITER
 Regulator Info 
Target Regulation Down regulation
Responsed Drug Trastuzumab Approved
 Drug Info 
Pathway Response Wnt signaling pathway hsa04310
Cell Process Glutathione synthesis
In-vitro Model ZR-75-1 Invasive breast carcinoma Homo sapiens CVCL_0588
T-47D Invasive breast carcinoma Homo sapiens CVCL_0553
SUM-159 (A mesenchymal triple-negative breast cancer cell line)
SK-BR-3 Breast adenocarcinoma Homo sapiens CVCL_0033
MDA-MB-468 Breast adenocarcinoma Homo sapiens CVCL_0419
MDA-MB-453 Breast adenocarcinoma Homo sapiens CVCL_0418
MDA-MB-361 Breast adenocarcinoma Homo sapiens CVCL_0620
MDA-MB-231 Breast adenocarcinoma Homo sapiens CVCL_0062
MCF-7 Invasive breast carcinoma Homo sapiens CVCL_0031
MCF-10A Normal Homo sapiens CVCL_0598
HEK293T Normal Homo sapiens CVCL_0063
BT-549 Invasive breast carcinoma Homo sapiens CVCL_1092
BT-474 Invasive breast carcinoma Homo sapiens CVCL_0179
AU565 Breast adenocarcinoma Homo sapiens CVCL_1074
In-vivo Model Luciferase-labeled rSKBR3 and MDA-MB-361 cells (1 × 107 cells) mixed with 1:1 Matrigel (Corning, 356237) were subcutaneously injected into the fat pads of mice. After a tumor was palpable, the mice were randomized into four groups (five mice per group), and they were treated with vehicle, trastuzumab (20 mg/kg, intraperitoneal administration), roblitinib (30 mg/kg, oral administration), or a combination of both drugs.
Experiment 3 Reporting the m6A-centered Disease Response [3]
Response Summary m6A-hypomethylation regulated FGFR4 phosphorylates GSK-3beta and activates beta-catenin/TCF4-Cystine/glutamate transporter (SLC7A11)/FPN1 signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer.
Responsed Disease Breast cancer [ICD-11: 2C60]
Target Regulator Methyltransferase-like 14 (METTL14) WRITER
 Regulator Info 
Target Regulation Down regulation
Responsed Drug Tucatinib Approved
 Drug Info 
Pathway Response Wnt signaling pathway hsa04310
Cell Process Glutathione synthesis
In-vitro Model ZR-75-1 Invasive breast carcinoma Homo sapiens CVCL_0588
T-47D Invasive breast carcinoma Homo sapiens CVCL_0553
SUM-159 (A mesenchymal triple-negative breast cancer cell line)
SK-BR-3 Breast adenocarcinoma Homo sapiens CVCL_0033
MDA-MB-468 Breast adenocarcinoma Homo sapiens CVCL_0419
MDA-MB-453 Breast adenocarcinoma Homo sapiens CVCL_0418
MDA-MB-361 Breast adenocarcinoma Homo sapiens CVCL_0620
MDA-MB-231 Breast adenocarcinoma Homo sapiens CVCL_0062
MCF-7 Invasive breast carcinoma Homo sapiens CVCL_0031
MCF-10A Normal Homo sapiens CVCL_0598
HEK293T Normal Homo sapiens CVCL_0063
BT-549 Invasive breast carcinoma Homo sapiens CVCL_1092
BT-474 Invasive breast carcinoma Homo sapiens CVCL_0179
AU565 Breast adenocarcinoma Homo sapiens CVCL_1074
In-vivo Model Luciferase-labeled rSKBR3 and MDA-MB-361 cells (1 × 107 cells) mixed with 1:1 Matrigel (Corning, 356237) were subcutaneously injected into the fat pads of mice. After a tumor was palpable, the mice were randomized into four groups (five mice per group), and they were treated with vehicle, trastuzumab (20 mg/kg, intraperitoneal administration), roblitinib (30 mg/kg, oral administration), or a combination of both drugs.
Pertuzumab [Approved]
 Drug Info 
In total 1 item(s) under this drug
Experiment 1 Reporting the m6A-centered Drug Response [3]
Response Summary m6A-hypomethylation regulated FGFR4 phosphorylates GSK-3beta and activates beta-catenin/TCF4-Cystine/glutamate transporter (SLC7A11)/FPN1 signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer.
Target Regulator Methyltransferase-like 14 (METTL14) WRITER
 Regulator Info 
Target Regulation Down regulation
Responsed Disease Breast cancer ICD-11: 2C60
 Disease Info 
Pathway Response Wnt signaling pathway hsa04310
Cell Process Glutathione synthesis
In-vitro Model ZR-75-1 Invasive breast carcinoma Homo sapiens CVCL_0588
T-47D Invasive breast carcinoma Homo sapiens CVCL_0553
SUM-159 (A mesenchymal triple-negative breast cancer cell line)
SK-BR-3 Breast adenocarcinoma Homo sapiens CVCL_0033
MDA-MB-468 Breast adenocarcinoma Homo sapiens CVCL_0419
MDA-MB-453 Breast adenocarcinoma Homo sapiens CVCL_0418
MDA-MB-361 Breast adenocarcinoma Homo sapiens CVCL_0620
MDA-MB-231 Breast adenocarcinoma Homo sapiens CVCL_0062
MCF-7 Invasive breast carcinoma Homo sapiens CVCL_0031
MCF-10A Normal Homo sapiens CVCL_0598
HEK293T Normal Homo sapiens CVCL_0063
BT-549 Invasive breast carcinoma Homo sapiens CVCL_1092
BT-474 Invasive breast carcinoma Homo sapiens CVCL_0179
AU565 Breast adenocarcinoma Homo sapiens CVCL_1074
In-vivo Model Luciferase-labeled rSKBR3 and MDA-MB-361 cells (1 × 107 cells) mixed with 1:1 Matrigel (Corning, 356237) were subcutaneously injected into the fat pads of mice. After a tumor was palpable, the mice were randomized into four groups (five mice per group), and they were treated with vehicle, trastuzumab (20 mg/kg, intraperitoneal administration), roblitinib (30 mg/kg, oral administration), or a combination of both drugs.
Trastuzumab [Approved]
 Drug Info 
In total 1 item(s) under this drug
Experiment 1 Reporting the m6A-centered Drug Response [3]
Response Summary m6A-hypomethylation regulated FGFR4 phosphorylates GSK-3beta and activates beta-catenin/TCF4-Cystine/glutamate transporter (SLC7A11)/FPN1 signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer.
Target Regulator Methyltransferase-like 14 (METTL14) WRITER
 Regulator Info 
Target Regulation Down regulation
Responsed Disease Breast cancer ICD-11: 2C60
 Disease Info 
Pathway Response Wnt signaling pathway hsa04310
Cell Process Glutathione synthesis
In-vitro Model ZR-75-1 Invasive breast carcinoma Homo sapiens CVCL_0588
T-47D Invasive breast carcinoma Homo sapiens CVCL_0553
SUM-159 (A mesenchymal triple-negative breast cancer cell line)
SK-BR-3 Breast adenocarcinoma Homo sapiens CVCL_0033
MDA-MB-468 Breast adenocarcinoma Homo sapiens CVCL_0419
MDA-MB-453 Breast adenocarcinoma Homo sapiens CVCL_0418
MDA-MB-361 Breast adenocarcinoma Homo sapiens CVCL_0620
MDA-MB-231 Breast adenocarcinoma Homo sapiens CVCL_0062
MCF-7 Invasive breast carcinoma Homo sapiens CVCL_0031
MCF-10A Normal Homo sapiens CVCL_0598
HEK293T Normal Homo sapiens CVCL_0063
BT-549 Invasive breast carcinoma Homo sapiens CVCL_1092
BT-474 Invasive breast carcinoma Homo sapiens CVCL_0179
AU565 Breast adenocarcinoma Homo sapiens CVCL_1074
In-vivo Model Luciferase-labeled rSKBR3 and MDA-MB-361 cells (1 × 107 cells) mixed with 1:1 Matrigel (Corning, 356237) were subcutaneously injected into the fat pads of mice. After a tumor was palpable, the mice were randomized into four groups (five mice per group), and they were treated with vehicle, trastuzumab (20 mg/kg, intraperitoneal administration), roblitinib (30 mg/kg, oral administration), or a combination of both drugs.
Tucatinib [Approved]
 Drug Info 
In total 1 item(s) under this drug
Experiment 1 Reporting the m6A-centered Drug Response [3]
Response Summary m6A-hypomethylation regulated FGFR4 phosphorylates GSK-3beta and activates beta-catenin/TCF4-Cystine/glutamate transporter (SLC7A11)/FPN1 signaling to drive anti-HER2 resistance. Knockdown of METTL14 significantly increased the expression level of FGFR4 in HER2-positive breast cancer cells. FGFR4 reduced the sensitivity of HER2-positive breast cancer to trastuzumab plus pertuzumab or tucatinib. These results pinpoint a mechanism of anti-HER2 resistance and provide a strategy for overcoming resistance via FGFR4 inhibition in recalcitrant HER2-positive breast cancer.
Target Regulator Methyltransferase-like 14 (METTL14) WRITER
 Regulator Info 
Target Regulation Down regulation
Responsed Disease Breast cancer ICD-11: 2C60
 Disease Info 
Pathway Response Wnt signaling pathway hsa04310
Cell Process Glutathione synthesis
In-vitro Model ZR-75-1 Invasive breast carcinoma Homo sapiens CVCL_0588
T-47D Invasive breast carcinoma Homo sapiens CVCL_0553
SUM-159 (A mesenchymal triple-negative breast cancer cell line)
SK-BR-3 Breast adenocarcinoma Homo sapiens CVCL_0033
MDA-MB-468 Breast adenocarcinoma Homo sapiens CVCL_0419
MDA-MB-453 Breast adenocarcinoma Homo sapiens CVCL_0418
MDA-MB-361 Breast adenocarcinoma Homo sapiens CVCL_0620
MDA-MB-231 Breast adenocarcinoma Homo sapiens CVCL_0062
MCF-7 Invasive breast carcinoma Homo sapiens CVCL_0031
MCF-10A Normal Homo sapiens CVCL_0598
HEK293T Normal Homo sapiens CVCL_0063
BT-549 Invasive breast carcinoma Homo sapiens CVCL_1092
BT-474 Invasive breast carcinoma Homo sapiens CVCL_0179
AU565 Breast adenocarcinoma Homo sapiens CVCL_1074
In-vivo Model Luciferase-labeled rSKBR3 and MDA-MB-361 cells (1 × 107 cells) mixed with 1:1 Matrigel (Corning, 356237) were subcutaneously injected into the fat pads of mice. After a tumor was palpable, the mice were randomized into four groups (five mice per group), and they were treated with vehicle, trastuzumab (20 mg/kg, intraperitoneal administration), roblitinib (30 mg/kg, oral administration), or a combination of both drugs.
References
Ref 1 The N6-methyladenosine modification enhances ferroptosis resistance through inhibiting SLC7A11 mRNA deadenylation in hepatoblastoma. Clin Transl Med. 2022 May;12(5):e778. doi: 10.1002/ctm2.778.
Ref 2 Hypoxia blocks ferroptosis of hepatocellular carcinoma via suppression of METTL14 triggered YTHDF2-dependent silencing of SLC7A11. J Cell Mol Med. 2021 Nov;25(21):10197-10212. doi: 10.1111/jcmm.16957. Epub 2021 Oct 5.
Ref 3 N6-methyladenosine regulated FGFR4 attenuates ferroptotic cell death in recalcitrant HER2-positive breast cancer. Nat Commun. 2022 May 13;13(1):2672. doi: 10.1038/s41467-022-30217-7.
Ref 4 METTL3 promotes lung adenocarcinoma tumor growth and inhibits ferroptosis by stabilizing SLC7A11 m(6)A modification. Cancer Cell Int. 2022 Jan 7;22(1):11. doi: 10.1186/s12935-021-02433-6.
Ref 5 RNA binding protein NKAP protects glioblastoma cells from ferroptosis by promoting SLC7A11 mRNA splicing in an m(6)A-dependent manner. Cell Death Dis. 2022 Jan 21;13(1):73. doi: 10.1038/s41419-022-04524-2.
Ref 6 The m(6)A reader YTHDC2 inhibits lung adenocarcinoma tumorigenesis by suppressing SLC7A11-dependent antioxidant function. Redox Biol. 2021 Jan;38:101801. doi: 10.1016/j.redox.2020.101801. Epub 2020 Nov 18.