HER-2 Signaling in Breast Cancer
Breast cancer tumorigenesis is a multi-step process where each step correlates with one or more distinct mutations in regulatory genes. Based on the set of genes that are mutated, breast cancer can be classified into hereditary or sporadic forms. HER-2/ERBB2 (Human Epidermal Growth Factor Receptor-2) mutations play a role in sporadic breast cancer. HER-2 is overexpressed in 25-30% of breast cancer cases. Overexpression of HER-2 occurs either through gene amplification or transcriptional deregulation...
Pathway Summary
Breast cancer tumorigenesis is a multi-step process where each step correlates with one or more distinct mutations in regulatory genes. Based on the set of genes that are mutated, breast cancer can be classified into hereditary or sporadic forms. HER-2/ERBB2 (Human Epidermal Growth Factor Receptor-2) mutations play a role in sporadic breast cancer. HER-2 is overexpressed in 25-30% of breast cancer cases. Overexpression of HER-2 occurs either through gene amplification or transcriptional deregulation.HER-2 is a member of the EGFR family; the other members include - EGFR/HER-1, HER-3/ERBB3 and HER-4/ERBB4. These transmembrane receptors undergo dimerization and transphosphorylation upon ligand binding. HER-2 can homodimerize or form heterodimers with HER-1 or HER-3. Overexpression of HER-2 changes the composition of the HER family dimers, significantly increasing HER-2 homo- and heterodimers. Moreover, HER-2 containing dimers have a prolonged signaling ability and evade signal attenuation, thus exacerbating the effects of receptor overexpression.HER-2 homodimers and heterodimers initiate various signaling pathways that influence breast cancer development. The most important oncogenic signaling function of the HER-2-HER-3 heterodimer is activation of the PI3K/AKT pathway. AKT mediates the downstream activation or inhibition of a number of proteins that are involved in cell growth, proliferation, survival, invasion and metastasis. The HER-2-HER-1 heterodimer mediates its signaling via Ras, PI3K and PLC-γ, resulting in cell hyperproliferation, cell migration and consequently tumorigenesis. Activation of HER-3 homodimers result in association with PAR6 and aPKC, which causes the dissociation of PAR3 from the active PAR3-PAR6-aPKC complex, leading to proliferation and protection against apoptosis. One important treatments for HER-2 positive breast cancer is Trastuzumab, a humanized monoclonal antibody binds the extracellular region of HER-2, causing de-activation, downregulation, and cell-killing by immune system effects. (Updated 09/04/2020)
HER-2 Signaling in Breast Cancer Genes list
Explore Genes related to HER-2 Signaling in Breast Cancer
AAASaladin WD repeat nucleoporin AHCTF1AT-hook containing transcription factor 1 AKT1AKT serine/threonine kinase 1 AKT1S1AKT1 substrate 1 AKT2AKT serine/threonine kinase 2 AKT3AKT serine/threonine kinase 3 ARAFA-Raf proto-oncogene, serine/threonine kinase AREGamphiregulin ARF1ADP ribosylation factor 1 ARF3ADP ribosylation factor 3 ARF4ADP ribosylation factor 4 ARF5ADP ribosylation factor 5 ARF6ADP ribosylation factor 6 BADBCL2 associated agonist of cell death BCL2L11BCL2 like 11 BIRC5baculoviral IAP repeat containing 5 BLKBLK proto-oncogene, Src family tyrosine kinase BRAFB-Raf proto-oncogene, serine/threonine kinase CASP3caspase 3 CASP6caspase 6 CASP7caspase 7 CASP9caspase 9 CCND1cyclin D1 CCNE1cyclin E1 CCNE2cyclin E2 CDC42cell division cycle 42 CDK4cyclin dependent kinase 4 CDKN1Acyclin dependent kinase inhibitor 1A CDKN1Bcyclin dependent kinase inhibitor 1B CHUKcomponent of inhibitor of nuclear factor kappa B kinase complex COPS6COP9 signalosome subunit 6 COX10cytochrome c oxidase assembly factor heme A:farnesyltransferase COX10 COX11cytochrome c oxidase copper chaperone COX11 COX15cytochrome c oxidase assembly homolog COX15 COX17cytochrome c oxidase copper chaperone COX17 COX4I1cytochrome c oxidase subunit 4I1 COX4I2cytochrome c oxidase subunit 4I2 COX5Acytochrome c oxidase subunit 5A COX5Bcytochrome c oxidase subunit 5B COX6A1cytochrome c oxidase subunit 6A1 COX6A2cytochrome c oxidase subunit 6A2 COX6B1cytochrome c oxidase subunit 6B1 COX6B2cytochrome c oxidase subunit 6B2 COX6Ccytochrome c oxidase subunit 6C COX7A1cytochrome c oxidase subunit 7A1 COX7A2cytochrome c oxidase subunit 7A2 COX7A2Lcytochrome c oxidase subunit 7A2 like COX7Bcytochrome c oxidase subunit 7B COX7B2cytochrome c oxidase subunit 7B2 COX7Ccytochrome c oxidase subunit 7C COX8Acytochrome c oxidase subunit 8A COX8Ccytochrome c oxidase subunit 8C DDX19BDEAD-box helicase 19B EGFepidermal growth factor EGFRepidermal growth factor receptor ELF1E74 like ETS transcription factor 1 ELF2E74 like ETS transcription factor 2 ELF3E74 like ETS transcription factor 3 ELF4E74 like ETS transcription factor 4 ELF5E74 like ETS transcription factor 5 ELK1ETS transcription factor ELK1 ELK3ETS transcription factor ELK3 ERASES cell expressed Ras ERBB2erb-b2 receptor tyrosine kinase 2 ERBB3erb-b2 receptor tyrosine kinase 3 ETS1ETS proto-oncogene 1, transcription factor ETS2ETS proto-oncogene 2, transcription factor FCER1AFc fragment of IgE receptor Ia FCER1GFc fragment of IgE receptor Ig FGRFGR proto-oncogene, Src family tyrosine kinase FOSFos proto-oncogene, AP-1 transcription factor subunit FOXO1forkhead box O1 FOXO3forkhead box O3 FRKfyn related Src family tyrosine kinase FYNFYN proto-oncogene, Src family tyrosine kinase GLE1GLE1 RNA export mediator GNB1LG protein subunit beta 1 like GRB2growth factor receptor bound protein 2 GSK3Aglycogen synthase kinase 3 alpha GSK3Bglycogen synthase kinase 3 beta H2BW2H2B.W histone 2 HBEGFheparin binding EGF like growth factor HCKHCK proto-oncogene, Src family tyrosine kinase HRASHRas proto-oncogene, GTPase IKBKBinhibitor of nuclear factor kappa B kinase subunit beta IKBKEinhibitor of nuclear factor kappa B kinase subunit epsilon IKBKGinhibitor of nuclear factor kappa B kinase regulatory subunit gamma IL1Ainterleukin 1 alpha ITGB1integrin subunit beta 1 ITGB2integrin subunit beta 2 ITGB3integrin subunit beta 3 ITGB4integrin subunit beta 4 ITGB5integrin subunit beta 5 ITGB6integrin subunit beta 6 ITGB7integrin subunit beta 7 ITGB8integrin subunit beta 8 JUNJun proto-oncogene, AP-1 transcription factor subunit KPNB1karyopherin subunit beta 1 KRASKRAS proto-oncogene, GTPase LCKLCK proto-oncogene, Src family tyrosine kinase LYNLYN proto-oncogene, Src family tyrosine kinase MAP2K1mitogen-activated protein kinase kinase 1 MAP2K2mitogen-activated protein kinase kinase 2 MAPK1mitogen-activated protein kinase 1 MAPK14mitogen-activated protein kinase 14 MAPK3mitogen-activated protein kinase 3 MDM2MDM2 proto-oncogene MIR21microRNA 21 MLST8MTOR associated protein, LST8 homolog MMP2matrix metallopeptidase 2 MRASmuscle RAS oncogene homolog MS4A2membrane spanning 4-domains A2 MT-CO1mitochondrially encoded cytochrome c oxidase I MT-CO2mitochondrially encoded cytochrome c oxidase II MT-CO3mitochondrially encoded cytochrome c oxidase III MTCL1microtubule crosslinking factor 1 MTORmechanistic target of rapamycin kinase MYCMYC proto-oncogene, bHLH transcription factor NDC1NDC1 transmembrane nucleoporin NFKB1nuclear factor kappa B subunit 1 NFKB2nuclear factor kappa B subunit 2 NFKBIANFKB inhibitor alpha NFKBIBNFKB inhibitor beta NFKBIDNFKB inhibitor delta NFKBIENFKB inhibitor epsilon NRASNRAS proto-oncogene, GTPase NRG1neuregulin 1 NUP107nucleoporin 107 NUP133nucleoporin 133 NUP153nucleoporin 153 NUP155nucleoporin 155 NUP160nucleoporin 160 NUP188nucleoporin 188 NUP205nucleoporin 205 NUP214nucleoporin 214 NUP35nucleoporin 35 NUP37nucleoporin 37 NUP42nucleoporin 42 NUP43nucleoporin 43 NUP50nucleoporin 50 NUP54nucleoporin 54 NUP58nucleoporin 58 NUP62nucleoporin 62 NUP85nucleoporin 85 NUP88nucleoporin 88 NUP93nucleoporin 93 NUP98nucleoporin 98 and 96 precursor PARD3par-3 family cell polarity regulator PARD6Apar-6 family cell polarity regulator alpha PARD6Bpar-6 family cell polarity regulator beta PARD6Gpar-6 family cell polarity regulator gamma PDK1pyruvate dehydrogenase kinase 1 PGRprogesterone receptor PIK3C2Aphosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 alpha PIK3C2Bphosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 beta PIK3C2Gphosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 gamma PIK3C3phosphatidylinositol 3-kinase catalytic subunit type 3 PIK3CAphosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha PIK3CBphosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta PIK3CDphosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta PIK3CGphosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma PIK3R1phosphoinositide-3-kinase regulatory subunit 1 PIK3R2phosphoinositide-3-kinase regulatory subunit 2 PIK3R3phosphoinositide-3-kinase regulatory subunit 3 PIK3R4phosphoinositide-3-kinase regulatory subunit 4 PIK3R5phosphoinositide-3-kinase regulatory subunit 5 PIK3R6phosphoinositide-3-kinase regulatory subunit 6 PLCG1phospholipase C gamma 1 PRKCAprotein kinase C alpha PRKCBprotein kinase C beta PRKCDprotein kinase C delta PRKCEprotein kinase C epsilon PRKCGprotein kinase C gamma PRKCHprotein kinase C eta PRKCIprotein kinase C iota PRKCQprotein kinase C theta PRKCZprotein kinase C zeta PRKD1protein kinase D1 PRKD3protein kinase D3 PTENphosphatase and tensin homolog PTGS2prostaglandin-endoperoxide synthase 2 RAE1ribonucleic acid export 1 RAF1Raf-1 proto-oncogene, serine/threonine kinase RALARAS like proto-oncogene A RALBRAS like proto-oncogene B RAP1ARAP1A, member of RAS oncogene family RAP1BRAP1B, member of RAS oncogene family RAP2ARAP2A, member of RAS oncogene family RAP2BRAP2B, member of RAS oncogene family RASD1ras related dexamethasone induced 1 RASD2RASD family member 2 RB1RB transcriptional corepressor 1 RBL1RB transcriptional corepressor like 1 RBL2RB transcriptional corepressor like 2 RELREL proto-oncogene, NF-kB subunit RELARELA proto-oncogene, NF-kB subunit RELBRELB proto-oncogene, NF-kB subunit RHEBRas homolog, mTORC1 binding RPS6ribosomal protein S6 RPS6KB1ribosomal protein S6 kinase B1 RPS6KB2ribosomal protein S6 kinase B2 RPTORregulatory associated protein of MTOR complex 1 RRASRAS related RRAS2RAS related 2 SEC13SEC13 homolog, nuclear pore and COPII coat complex component SEH1LSEH1 like nucleoporin SMAD3SMAD family member 3 SMAD4SMAD family member 4 SOS1SOS Ras/Rac guanine nucleotide exchange factor 1 SOS2SOS Ras/Rho guanine nucleotide exchange factor 2 SP1Sp1 transcription factor SRCSRC proto-oncogene, non-receptor tyrosine kinase STAT3signal transducer and activator of transcription 3 TGFAtransforming growth factor alpha TP53tumor protein p53 TPRtranslocated promoter region, nuclear basket protein TSC1TSC complex subunit 1 TSC2TSC complex subunit 2 XIAPX-linked inhibitor of apoptosis YES1YES proto-oncogene 1, Src family tyrosine kinase
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