Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10258)
Regulator Name Protein LYRIC (MTDH)
Synonyms
AEG1, LYRIC; 3D3/LYRIC; Astrocyte elevated gene-1 protein; Lysine-rich CEACAM1 co-isolated protein; Metadherin; Metastasis adhesion protein
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Gene Name MTDH
Gene ID 92140
Regulator Type Protein coding
Uniprot ID Q86UE4
Sequence
MAARSWQDELAQQAEEGSARLREMLSVGLGFLRTELGLDLGLEPKRYPGWVILVGTGALG
LLLLFLLGYGWAAACAGARKKRRSPPRKREEAAAVPAAAPDDLALLKNLRSEEQKKKNRK
KLSEKPKPNGRTVEVAEGEAVRTPQSVTAKQPPEIDKKNEKSKKNKKKSKSDAKAVQNSS
RHDGKEVDEGAWETKISHREKRQQRKRDKVLTDSGSLDSTIPGIENTITVTTEQLTTASF
PVGSKKNKGDSHLNVQVSNFKSGKGDSTLQVSSGLNENLTVNGGGWNEKSVKLSSQISAG
EEKWNSVSPASAGKRKTEPSAWSQDTGDANTNGKDWGRSWSDRSIFSGIGSTAEPVSQST
TSDYQWDVSRNQPYIDDEWSGLNGLSSADPNSDWNAPAEEWGNWVDEERASLLKSQEPIP
DDQKVSDDDKEKGEGALPTGKSKKKKKKKKKQGEDNSTAQDTEELEKEIREDLPVNTSKT
RPKQEKAFSLKTISTSDPAEVLVKNSQPIKTLPPATSTEPSVILSKSDSDKSSSQVPPIL
QETDKSKSNTKQNSVPPSQTKSETSWESPKQIKKKKKARRET

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Function
Down-regulates SLC1A2/EAAT2 promoter activity when expressed ectopically. Activates the nuclear factor kappa-B (NF-kappa-B) transcription factor. Promotes anchorage-independent growth of immortalized melanocytes and astrocytes which is a key component in tumor cell expansion. Promotes lung metastasis and also has an effect on bone and brain metastasis, possibly by enhancing the seeding of tumor cells to the target organ endothelium. Induces chemoresistance.

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HGNC ID
HGNC:29608
KEGG ID hsa:92140
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
MTDH can regulate the following target(s), and cause disease/drug response(s). You can browse detail information of target(s) or disease/drug response(s).
Browse Target
Browse Disease
Phospholipid hydroperoxide glutathione peroxidase (GPX4) [Suppressor]
 Target Info 
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Target for Ferroptosis Suppressor
Responsed Disease Lung cancer ICD-11: 2C25
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 A-549 cells Lung adenocarcinoma Homo sapiens CVCL_0023
NCI-H1975 cells Lung adenocarcinoma Homo sapiens CVCL_1511
DMS53 cells Lung small cell carcinoma Homo sapiens CVCL_1177
DMS 273 cells Lung small cell carcinoma Homo sapiens CVCL_1176
KLE cells Endometrial adenocarcinoma Homo sapiens CVCL_1329
AN3CA cells Endometrial adenocarcinoma Homo sapiens CVCL_0028
RL95-2 cells Endometrial adenosquamous carcinoma Homo sapiens CVCL_0505
HEC-1-A cells Endometrial adenocarcinoma Homo sapiens CVCL_0293
Ishikawa cells Endometrial adenocarcinoma Homo sapiens CVCL_2529
MDA-MB-231 cells Breast adenocarcinoma Homo sapiens CVCL_0062
MCF-7 cells Breast carcinoma Homo sapiens CVCL_0031
Hec50 cells Endometrial adenocarcinoma Homo sapiens CVCL_2929
In Vivo Model
To generate tumor xenograft models, 5 x 106 MTDH WT and KO MDA-MB-231 cells were injected into the second and fifth mammary fat pads (both sides, total four sites) of the NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG, Jackson Laboratories, Bar Harbor, ME) immunodeficient female mice. To study the metastasis from this orthotopic mouse model, tumor volumes were allowed to grow to ~1000 mm3, after which livers were resected to examine incidence as well as tumor burden of liver metastasis.

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Response regulation Metadherin (MTDH) confers a therapy-resistant mesenchymal-high cell state and enhanced sensitivity to inducers of ferroptosis. Mechanistically, MTDH inhibited GPx4, as well as the solute carrier family 3 member 2 (SLC3A2, a system Xc-heterodimerization partner), at both the messenger RNA and protein levels in Lung adenocarcinoma.
4F2 cell-surface antigen heavy chain (SLC3A2) [Suppressor]
 Target Info 
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Target for Ferroptosis Suppressor
Responsed Disease Lung cancer ICD-11: 2C25
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 A-549 cells Lung adenocarcinoma Homo sapiens CVCL_0023
NCI-H1975 cells Lung adenocarcinoma Homo sapiens CVCL_1511
DMS53 cells Lung small cell carcinoma Homo sapiens CVCL_1177
DMS 273 cells Lung small cell carcinoma Homo sapiens CVCL_1176
KLE cells Endometrial adenocarcinoma Homo sapiens CVCL_1329
AN3CA cells Endometrial adenocarcinoma Homo sapiens CVCL_0028
RL95-2 cells Endometrial adenosquamous carcinoma Homo sapiens CVCL_0505
HEC-1-A cells Endometrial adenocarcinoma Homo sapiens CVCL_0293
Ishikawa cells Endometrial adenocarcinoma Homo sapiens CVCL_2529
MDA-MB-231 cells Breast adenocarcinoma Homo sapiens CVCL_0062
MCF-7 cells Breast carcinoma Homo sapiens CVCL_0031
Hec50 cells Endometrial adenocarcinoma Homo sapiens CVCL_2929
In Vivo Model
To generate tumor xenograft models, 5 x 106 MTDH WT and KO MDA-MB-231 cells were injected into the second and fifth mammary fat pads (both sides, total four sites) of the NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG, Jackson Laboratories, Bar Harbor, ME) immunodeficient female mice. To study the metastasis from this orthotopic mouse model, tumor volumes were allowed to grow to ~1000 mm3, after which livers were resected to examine incidence as well as tumor burden of liver metastasis.

    Click to Show/Hide
Response regulation Metadherin (MTDH) confers a therapy-resistant mesenchymal-high cell state and enhanced sensitivity to inducers of ferroptosis. Mechanistically, MTDH inhibited GPx4, as well as the solute carrier family 3 member 2 (SLC3A2, a system Xc-heterodimerization partner), at both the messenger RNA and protein levels in Lung adenocarcinoma.
Lung cancer [ICD-11: 2C25]
 Disease Info 
In total 2 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Protein LYRIC (MTDH) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 A-549 cells Lung adenocarcinoma Homo sapiens CVCL_0023
NCI-H1975 cells Lung adenocarcinoma Homo sapiens CVCL_1511
DMS53 cells Lung small cell carcinoma Homo sapiens CVCL_1177
DMS 273 cells Lung small cell carcinoma Homo sapiens CVCL_1176
KLE cells Endometrial adenocarcinoma Homo sapiens CVCL_1329
AN3CA cells Endometrial adenocarcinoma Homo sapiens CVCL_0028
RL95-2 cells Endometrial adenosquamous carcinoma Homo sapiens CVCL_0505
HEC-1-A cells Endometrial adenocarcinoma Homo sapiens CVCL_0293
Ishikawa cells Endometrial adenocarcinoma Homo sapiens CVCL_2529
MDA-MB-231 cells Breast adenocarcinoma Homo sapiens CVCL_0062
MCF-7 cells Breast carcinoma Homo sapiens CVCL_0031
Hec50 cells Endometrial adenocarcinoma Homo sapiens CVCL_2929
In Vivo Model
To generate tumor xenograft models, 5 x 106 MTDH WT and KO MDA-MB-231 cells were injected into the second and fifth mammary fat pads (both sides, total four sites) of the NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG, Jackson Laboratories, Bar Harbor, ME) immunodeficient female mice. To study the metastasis from this orthotopic mouse model, tumor volumes were allowed to grow to ~1000 mm3, after which livers were resected to examine incidence as well as tumor burden of liver metastasis.

    Click to Show/Hide
Response regulation Metadherin (MTDH) confers a therapy-resistant mesenchymal-high cell state and enhanced sensitivity to inducers of ferroptosis. Mechanistically, MTDH inhibited GPx4, as well as the solute carrier family 3 member 2 (SLC3A2, a system Xc-heterodimerization partner), at both the messenger RNA and protein levels in Lung adenocarcinoma.
Experiment 2 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Protein LYRIC (MTDH) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 A-549 cells Lung adenocarcinoma Homo sapiens CVCL_0023
NCI-H1975 cells Lung adenocarcinoma Homo sapiens CVCL_1511
DMS53 cells Lung small cell carcinoma Homo sapiens CVCL_1177
DMS 273 cells Lung small cell carcinoma Homo sapiens CVCL_1176
KLE cells Endometrial adenocarcinoma Homo sapiens CVCL_1329
AN3CA cells Endometrial adenocarcinoma Homo sapiens CVCL_0028
RL95-2 cells Endometrial adenosquamous carcinoma Homo sapiens CVCL_0505
HEC-1-A cells Endometrial adenocarcinoma Homo sapiens CVCL_0293
Ishikawa cells Endometrial adenocarcinoma Homo sapiens CVCL_2529
MDA-MB-231 cells Breast adenocarcinoma Homo sapiens CVCL_0062
MCF-7 cells Breast carcinoma Homo sapiens CVCL_0031
Hec50 cells Endometrial adenocarcinoma Homo sapiens CVCL_2929
In Vivo Model
To generate tumor xenograft models, 5 x 106 MTDH WT and KO MDA-MB-231 cells were injected into the second and fifth mammary fat pads (both sides, total four sites) of the NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG, Jackson Laboratories, Bar Harbor, ME) immunodeficient female mice. To study the metastasis from this orthotopic mouse model, tumor volumes were allowed to grow to ~1000 mm3, after which livers were resected to examine incidence as well as tumor burden of liver metastasis.

    Click to Show/Hide
Response regulation Metadherin (MTDH) confers a therapy-resistant mesenchymal-high cell state and enhanced sensitivity to inducers of ferroptosis. Mechanistically, MTDH inhibited GPx4, as well as the solute carrier family 3 member 2 (SLC3A2, a system Xc-heterodimerization partner), at both the messenger RNA and protein levels in Lung adenocarcinoma.
References
Ref 1 Metadherin enhances vulnerability of cancer cells to ferroptosis. Cell Death Dis. 2019 Sep 17;10(10):682. doi: 10.1038/s41419-019-1897-2.