General Information of the Ferroptosis Regulator (ID: REG10054)
Regulator Name Epidermal growth factor receptor (EGFR)
Synonyms
ERBB, ERBB1, HER1; Proto-oncogene c-ErbB-1; Receptor tyrosine-protein kinase erbB-1
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Gene Name EGFR
Gene ID 1956
Regulator Type Protein coding
Uniprot ID P00533
Sequence
MRPSGTAGAALLALLAALCPASRALEEKKVCQGTSNKLTQLGTFEDHFLSLQRMFNNCEV
VLGNLEITYVQRNYDLSFLKTIQEVAGYVLIALNTVERIPLENLQIIRGNMYYENSYALA
VLSNYDANKTGLKELPMRNLQEILHGAVRFSNNPALCNVESIQWRDIVSSDFLSNMSMDF
QNHLGSCQKCDPSCPNGSCWGAGEENCQKLTKIICAQQCSGRCRGKSPSDCCHNQCAAGC
TGPRESDCLVCRKFRDEATCKDTCPPLMLYNPTTYQMDVNPEGKYSFGATCVKKCPRNYV
VTDHGSCVRACGADSYEMEEDGVRKCKKCEGPCRKVCNGIGIGEFKDSLSINATNIKHFK
NCTSISGDLHILPVAFRGDSFTHTPPLDPQELDILKTVKEITGFLLIQAWPENRTDLHAF
ENLEIIRGRTKQHGQFSLAVVSLNITSLGLRSLKEISDGDVIISGNKNLCYANTINWKKL
FGTSGQKTKIISNRGENSCKATGQVCHALCSPEGCWGPEPRDCVSCRNVSRGRECVDKCN
LLEGEPREFVENSECIQCHPECLPQAMNITCTGRGPDNCIQCAHYIDGPHCVKTCPAGVM
GENNTLVWKYADAGHVCHLCHPNCTYGCTGPGLEGCPTNGPKIPSIATGMVGALLLLLVV
ALGIGLFMRRRHIVRKRTLRRLLQERELVEPLTPSGEAPNQALLRILKETEFKKIKVLGS
GAFGTVYKGLWIPEGEKVKIPVAIKELREATSPKANKEILDEAYVMASVDNPHVCRLLGI
CLTSTVQLITQLMPFGCLLDYVREHKDNIGSQYLLNWCVQIAKGMNYLEDRRLVHRDLAA
RNVLVKTPQHVKITDFGLAKLLGAEEKEYHAEGGKVPIKWMALESILHRIYTHQSDVWSY
GVTVWELMTFGSKPYDGIPASEISSILEKGERLPQPPICTIDVYMIMVKCWMIDADSRPK
FRELIIEFSKMARDPQRYLVIQGDERMHLPSPTDSNFYRALMDEEDMDDVVDADEYLIPQ
QGFFSSPSTSRTPLLSSLSATSNNSTVACIDRNGLQSCPIKEDSFLQRYSSDPTGALTED
SIDDTFLPVPEYINQSVPKRPAGSVQNPVYHNQPLNPAPSRDPHYQDPHSTAVGNPEYLN
TVQPTCVNSTFDSPAHWAQKGSHQISLDNPDYQQDFFPKEAKPNGIFKGSTAENAEYLRV
APQSSEFIGA

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Family Tyr protein kinase family
Function
Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses. Known ligands include EGF, TGFA/TGF-alpha, AREG, epigen/EPGN, BTC/betacellulin, epiregulin/EREG and HBEGF/heparin- binding EGF. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation on key cytoplasmic residues. The phosphorylated receptor recruits adapter proteins like GRB2 which in turn activates complex downstream signaling cascades. Activates at least 4 major downstream signaling cascades including the RAS-RAF-MEK-ERK, PI3 kinase-AKT, PLCgamma-PKC and STATs modules. May also activate the NF-kappa-B signaling cascade. Also directly phosphorylates other proteins like RGS16, activating its GTPase activity and probably coupling the EGF receptor signaling to the G protein-coupled receptor signaling. Also phosphorylates MUC1 and increases its interaction with SRC and CTNNB1/beta-catenin. Positively regulates cell migration via interaction with CCDC88A/GIV which retains EGFR at the cell membrane following ligand stimulation, promoting EGFR signaling which triggers cell migration. Plays a role in enhancing learning and memory performance. Plays a role in mammalian pain signaling (long-lasting hypersensitivity).

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HGNC ID
HGNC:3236
KEGG ID hsa:1956
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
EGFR 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]
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
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
hTERT-HME1 cells Normal Homo sapiens CVCL_3383
H1650-ER1 cells Minimally invasive lung adenocarcinoma Homo sapiens CVCL_4V01
In Vivo Model
2.5 x 105 NCI-H1650 cells were inoculated 1:1 in Matrigel: PBS (100 mL) by subcutaneous injection into eight non-obese diabetic (NOD) severe combined immunodeficiency (SCID) gamma male mice. Tumors were allowed to engraft and grow for 30 days (tumor volume averaged ~200 mm3) and mice treated by intraperitoneal (i.p.) injection with 100 mg/kg cyst(e)inase or 100 mg/kg heat-inactivated cyst(e)inase (n = 4 ea.) on day 30, with a second dose given on day 33. Mice were necropsied 24 hr after the second dose.

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Response regulation In non-small-cell lung cancer (NSCLC) cells, active MAPK signaling downstream of active EGFR can sensitize cells to ferroptosis upon cystine depletion. Sensitization involves both impaired detoxification of lipid peroxides, due to reduced expression of GPX4, and generation of hydrogen peroxide, via NOX4.
NADPH oxidase 4 (NOX4) [Driver]
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Target for Ferroptosis Driver
Responsed Disease Lung cancer ICD-11: 2C25
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
hTERT-HME1 cells Normal Homo sapiens CVCL_3383
H1650-ER1 cells Minimally invasive lung adenocarcinoma Homo sapiens CVCL_4V01
In Vivo Model
2.5 x 105 NCI-H1650 cells were inoculated 1:1 in Matrigel: PBS (100 mL) by subcutaneous injection into eight non-obese diabetic (NOD) severe combined immunodeficiency (SCID) gamma male mice. Tumors were allowed to engraft and grow for 30 days (tumor volume averaged ~200 mm3) and mice treated by intraperitoneal (i.p.) injection with 100 mg/kg cyst(e)inase or 100 mg/kg heat-inactivated cyst(e)inase (n = 4 ea.) on day 30, with a second dose given on day 33. Mice were necropsied 24 hr after the second dose.

    Click to Show/Hide
Response regulation In non-small-cell lung cancer (NSCLC) cells, active MAPK signaling downstream of active EGFR can sensitize cells to ferroptosis upon cystine depletion. Sensitization involves both impaired detoxification of lipid peroxides, due to reduced expression of GPX4, and generation of hydrogen peroxide, via NOX4.
Lung cancer [ICD-11: 2C25]
In total 2 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Epidermal growth factor receptor (EGFR) Protein coding
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
hTERT-HME1 cells Normal Homo sapiens CVCL_3383
H1650-ER1 cells Minimally invasive lung adenocarcinoma Homo sapiens CVCL_4V01
In Vivo Model
2.5 x 105 NCI-H1650 cells were inoculated 1:1 in Matrigel: PBS (100 mL) by subcutaneous injection into eight non-obese diabetic (NOD) severe combined immunodeficiency (SCID) gamma male mice. Tumors were allowed to engraft and grow for 30 days (tumor volume averaged ~200 mm3) and mice treated by intraperitoneal (i.p.) injection with 100 mg/kg cyst(e)inase or 100 mg/kg heat-inactivated cyst(e)inase (n = 4 ea.) on day 30, with a second dose given on day 33. Mice were necropsied 24 hr after the second dose.

    Click to Show/Hide
Response regulation In non-small-cell lung cancer (NSCLC) cells, active MAPK signaling downstream of active EGFR can sensitize cells to ferroptosis upon cystine depletion. Sensitization involves both impaired detoxification of lipid peroxides, due to reduced expression of GPX4, and generation of hydrogen peroxide, via NOX4.
Experiment 2 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Epidermal growth factor receptor (EGFR) Protein coding
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
hTERT-HME1 cells Normal Homo sapiens CVCL_3383
H1650-ER1 cells Minimally invasive lung adenocarcinoma Homo sapiens CVCL_4V01
In Vivo Model
2.5 x 105 NCI-H1650 cells were inoculated 1:1 in Matrigel: PBS (100 mL) by subcutaneous injection into eight non-obese diabetic (NOD) severe combined immunodeficiency (SCID) gamma male mice. Tumors were allowed to engraft and grow for 30 days (tumor volume averaged ~200 mm3) and mice treated by intraperitoneal (i.p.) injection with 100 mg/kg cyst(e)inase or 100 mg/kg heat-inactivated cyst(e)inase (n = 4 ea.) on day 30, with a second dose given on day 33. Mice were necropsied 24 hr after the second dose.

    Click to Show/Hide
Response regulation In non-small-cell lung cancer (NSCLC) cells, active MAPK signaling downstream of active EGFR can sensitize cells to ferroptosis upon cystine depletion. Sensitization involves both impaired detoxification of lipid peroxides, due to reduced expression of GPX4, and generation of hydrogen peroxide, via NOX4.
References
Ref 1 Oncogene-Selective Sensitivity to Synchronous Cell Death following Modulation of the Amino Acid Nutrient Cystine. Cell Rep. 2017 Mar 14;18(11):2547-2556. doi: 10.1016/j.celrep.2017.02.054.