HCSGD entry for ERBB2
1. General information
| Official gene symbol | ERBB2 |
|---|---|
| Entrez ID | 2064 |
| Gene full name | v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, neuro/glioblastoma derived oncogene homolog (avian) |
| Other gene symbols | CD340 HER-2 HER-2/neu HER2 MLN 19 NEU NGL TKR1 |
| Links to Entrez Gene | Links to Entrez Gene |
2. Neighbors in the network
3. Gene ontology annotation
GO ID | GO term | Evidence | Category |
|---|---|---|---|
| GO:0001042 | RNA polymerase I core binding | IDA | molecular_function |
| GO:0001934 | Positive regulation of protein phosphorylation | IEA ISS | biological_process |
| GO:0004713 | Protein tyrosine kinase activity | IDA IEA IGI TAS | molecular_function |
| GO:0004714 | Transmembrane receptor protein tyrosine kinase activity | IDA IEA | molecular_function |
| GO:0004716 | Receptor signaling protein tyrosine kinase activity | IEA | molecular_function |
| GO:0004888 | Transmembrane signaling receptor activity | IDA | molecular_function |
| GO:0005006 | Epidermal growth factor-activated receptor activity | NAS | molecular_function |
| GO:0005515 | Protein binding | IPI | molecular_function |
| GO:0005524 | ATP binding | IEA | molecular_function |
| GO:0005634 | Nucleus | IDA | cellular_component |
| GO:0005886 | Plasma membrane | NAS TAS | cellular_component |
| GO:0006351 | Transcription, DNA-templated | IEA | biological_process |
| GO:0006468 | Protein phosphorylation | TAS | biological_process |
| GO:0007165 | Signal transduction | IDA | biological_process |
| GO:0007166 | Cell surface receptor signaling pathway | IDA | biological_process |
| GO:0007167 | Enzyme linked receptor protein signaling pathway | TAS | biological_process |
| GO:0007169 | Transmembrane receptor protein tyrosine kinase signaling pathway | IDA IEA TAS | biological_process |
| GO:0007173 | Epidermal growth factor receptor signaling pathway | TAS | biological_process |
| GO:0007399 | Nervous system development | TAS | biological_process |
| GO:0007411 | Axon guidance | TAS | biological_process |
| GO:0007422 | Peripheral nervous system development | IEA | biological_process |
| GO:0007507 | Heart development | IEA TAS | biological_process |
| GO:0007528 | Neuromuscular junction development | IEA | biological_process |
| GO:0008022 | Protein C-terminus binding | IPI | molecular_function |
| GO:0008045 | Motor neuron axon guidance | IEA | biological_process |
| GO:0008283 | Cell proliferation | TAS | biological_process |
| GO:0008543 | Fibroblast growth factor receptor signaling pathway | TAS | biological_process |
| GO:0010008 | Endosome membrane | IDA | cellular_component |
| GO:0014065 | Phosphatidylinositol 3-kinase signaling | IDA | biological_process |
| GO:0016020 | Membrane | IEA | cellular_component |
| GO:0016021 | Integral component of membrane | NAS | cellular_component |
| GO:0016323 | Basolateral plasma membrane | IDA | cellular_component |
| GO:0016324 | Apical plasma membrane | IEA | cellular_component |
| GO:0018108 | Peptidyl-tyrosine phosphorylation | IDA IGI NAS TAS | biological_process |
| GO:0019838 | Growth factor binding | IDA | molecular_function |
| GO:0019903 | Protein phosphatase binding | IPI | molecular_function |
| GO:0023014 | Signal transduction by phosphorylation | TAS | biological_process |
| GO:0030307 | Positive regulation of cell growth | IMP | biological_process |
| GO:0030879 | Mammary gland development | TAS | biological_process |
| GO:0031410 | Cytoplasmic vesicle | IEA | cellular_component |
| GO:0032321 | Positive regulation of Rho GTPase activity | IEA ISS | biological_process |
| GO:0032886 | Regulation of microtubule-based process | IDA | biological_process |
| GO:0033088 | Negative regulation of immature T cell proliferation in thymus | IEA | biological_process |
| GO:0038095 | Fc-epsilon receptor signaling pathway | TAS | biological_process |
| GO:0042060 | Wound healing | IDA | biological_process |
| GO:0042552 | Myelination | IEA | biological_process |
| GO:0042802 | Identical protein binding | IPI | molecular_function |
| GO:0043125 | ErbB-3 class receptor binding | TAS | molecular_function |
| GO:0043235 | Receptor complex | IDA TAS | cellular_component |
| GO:0043406 | Positive regulation of MAP kinase activity | IDA | biological_process |
| GO:0045087 | Innate immune response | TAS | biological_process |
| GO:0045727 | Positive regulation of translation | IMP | biological_process |
| GO:0045765 | Regulation of angiogenesis | NAS | biological_process |
| GO:0045785 | Positive regulation of cell adhesion | IDA | biological_process |
| GO:0045943 | Positive regulation of transcription from RNA polymerase I promoter | IMP | biological_process |
| GO:0045945 | Positive regulation of transcription from RNA polymerase III promoter | IDA | biological_process |
| GO:0046777 | Protein autophosphorylation | IDA | biological_process |
| GO:0046982 | Protein heterodimerization activity | IDA IPI NAS | molecular_function |
| GO:0046983 | Protein dimerization activity | NAS | molecular_function |
| GO:0048011 | Neurotrophin TRK receptor signaling pathway | TAS | biological_process |
| GO:0048015 | Phosphatidylinositol-mediated signaling | NAS TAS | biological_process |
| GO:0048471 | Perinuclear region of cytoplasm | IEA | cellular_component |
| GO:0050679 | Positive regulation of epithelial cell proliferation | IDA | biological_process |
| GO:0070372 | Regulation of ERK1 and ERK2 cascade | IMP | biological_process |
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4. Expression levels in datasets
- Meta-analysis result
| p-value up | p-value down | FDR up | FDR down |
|---|---|---|---|
| 0.7039193496 | 0.1224928840 | 0.9999902473 | 0.6716948333 |
- Individual experiment result
( "-" represent NA in the specific microarray platform )
( "-" represent NA in the specific microarray platform )
| Data source | Up or down | Log fold change |
|---|---|---|
| GSE11954 | Down | -0.1572489675 |
| GSE13712_SHEAR | Down | -0.1236048239 |
| GSE13712_STATIC | Down | -0.2347200057 |
| GSE19018 | Up | 0.0602823718 |
| GSE19899_A1 | Down | -0.3169518931 |
| GSE19899_A2 | Down | -0.2653048856 |
| PubMed_21979375_A1 | Down | -0.5991207396 |
| PubMed_21979375_A2 | Up | 0.0244293220 |
| GSE35957 | Up | 0.1706330577 |
| GSE36640 | Up | 0.3617738796 |
| GSE54402 | Down | -0.8628673626 |
| GSE9593 | Up | 0.2710424786 |
| GSE43922 | Down | -0.5811450060 |
| GSE24585 | Up | 0.0261184182 |
| GSE37065 | Down | -0.1713720526 |
| GSE28863_A1 | Up | 0.4866365649 |
| GSE28863_A2 | Up | 0.2941470665 |
| GSE28863_A3 | Down | -0.2337191989 |
| GSE28863_A4 | Down | -0.0269253958 |
| GSE48662 | Up | 0.4269488677 |
5. Regulation relationships with compounds/drugs/microRNAs
- Compounds
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- Drugs
Name | Drug | Accession number |
|---|---|---|
| Trastuzumab | DB00072 | BTD00098 | BIOD00098 |
| IGN311 | DB04988 | - |
| XL647 | DB05007 | - |
| Trastuzumab emtansine | DB05773 | - |
| Pertuzumab | DB06366 | - |
| Afatinib | DB08916 | - |
- MicroRNAs
- mirTarBase
MiRNA_name | mirBase ID | miRTarBase ID | Experiment | Support type | References (Pubmed ID) |
|---|---|---|---|---|---|
| hsa-miR-559 | MIMAT0003223 | MIRT000036 | Luciferase reporter assay//Reporter assay;Other | Functional MTI | 19486885 |
| hsa-miR-548d-3p | MIMAT0003323 | MIRT000037 | Luciferase reporter assay//Reporter assay;Other | Functional MTI | 19486885 |
| hsa-miR-125b-5p | MIMAT0000423 | MIRT002939 | Western blot | Functional MTI | 19825990 |
| hsa-miR-125b-5p | MIMAT0000423 | MIRT002939 | Luciferase reporter assay//Northern blot//qRT-PCR//Western blot | Functional MTI | 17110380 |
| hsa-miR-125b-5p | MIMAT0000423 | MIRT002939 | Luciferase reporter assay//Microarray//Western blot | Functional MTI | 20864407 |
| hsa-miR-21-5p | MIMAT0000076 | MIRT004318 | qRT-PCR//Western blot | Functional MTI | 19419954 |
| hsa-miR-125a-5p | MIMAT0000443 | MIRT005118 | Luciferase reporter assay//Northern blot//qRT-PCR//Western blot | Functional MTI | 17110380 |
| hsa-miR-125a-5p | MIMAT0000443 | MIRT005118 | Luciferase reporter assay | Functional MTI | 21220473 |
| hsa-miR-331-3p | MIMAT0000760 | MIRT005805 | Luciferase reporter assay//Microarray//Western blot | Functional MTI | 20864407 |
| hsa-miR-205-5p | MIMAT0000266 | MIRT006982 | qRT-PCR//Western blot | Functional MTI | 21787752 |
| hsa-miR-199b-5p | MIMAT0000263 | MIRT007152 | Luciferase reporter assay//qRT-PCR//Western blot | Functional MTI | 23296799 |
| hsa-miR-199a-5p | MIMAT0000231 | MIRT007265 | Western blot | Functional MTI | 23437196 |
| hsa-miR-124-3p | MIMAT0000422 | MIRT023179 | Microarray | Functional MTI (Weak) | 18668037 |
| hsa-miR-326 | MIMAT0000756 | MIRT043637 | CLASH | Functional MTI (Weak) | 23622248 |
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- mirRecord
MicroRNA name | mirBase ID | Target site number | MiRNA mature ID | Test method inter | MiRNA regulation site | Reporter target site | Pubmed ID |
|---|---|---|---|---|---|---|---|
| hsa-miR-125a-5p | MIMAT0000443 | 1 | hsa-miR-125a-5p | {Western blot} | {overexpression by mature miRNA transfection} | 17110380 | |
| hsa-miR-125b-5p | MIMAT0000423 | 1 | hsa-miR-125b | {Western blot} | {overexpression by mature miRNA transfection} | 17110380 | |
| hsa-miR-331-3p | MIMAT0000760 | 2 | hsa-miR-331-3p | {Western blot} | {overexpression by miRNA precursor transfection} | 19584056 | |
| hsa-miR-331-3p | MIMAT0000760 | 1 | hsa-miR-331-3p | {Western blot} | {overexpression by miRNA precursor transfection} | 19584056 | |
| hsa-miR-548d-3p | MIMAT0003323 | 1 | hsa-miR-548d-3p | 19486885 | |||
| hsa-miR-559 | MIMAT0003223 | 1 | hsa-miR-559 | 19486885 |
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6. Text-mining results about the gene
Gene occurances in abstracts of cellular senescence-associated articles: 24 abstracts the gene occurs.
PubMed ID of the article | Sentenece the gene occurs |
|---|---|
| 26420857 | PURPOSE: Aberrant regulation of the EGF receptor family (EGFR, HER2, HER3, HER4) contributes to tumorigenesis and metastasis in epithelial cancers |
| 26420857 | Pan-HER represents a novel molecular targeted therapeutic composed of a mixture of six monoclonal antibodies against EGFR, HER2, and HER3 |
| 26260680 | RESULTS: Using breast cancer cells expressing p95HER2, a constitutively active fragment of the proto-oncogene HER2 that induces OIS, we show that the extracellular domains of a variety of membrane-bound proteins form part of the senescence secretome |
| 26168818 | Antiangiogenic and antitumor activities of berberine derivative NAX014 compound in a transgenic murine model of HER2/neu-positive mammary carcinoma |
| 26168818 | We recently demonstrated that BBR and its synthetic derivative 13-(4-chlorophenylethyl)berberine iodide, NAX014, exert antiproliferative activity against HER2-overexpressing breast cancer cells, inducing apoptosis, modulating the expression of cell cycle checkpoint molecules involved in cell senescence, and reducing both HER2 expression and phosphorylation on tumor cells |
| 26168818 | The results of the present study indicate that NAX014 is more effective than BBR in exerting anticancer activity delaying the development of mammary tumors in mice transgenic for the HER-2/neu oncogene |
| 25972601 | OIS can be triggered by ectopic overexpression of HER2, a receptor tyrosine kinase and the driving oncogene in a subtype of human breast cancer |
| 25972601 | RESULTS: We found that senescent cells arise constantly in different models of advanced breast cancers overexpressing HER2 and constitute approximately 5% of tumor cells |
| 25594009 | Targeting HER2(+) breast cancer: the TBK1/IKKepsilon axis |
| 25594009 | HER2(+) breast cancer (BC) is a highly aggressive subtype, affecting ~20% of BC patients |
| 25594009 | Current treatments include adjuvant or neoadjuvant chemotherapy plus anti-HER2 agents such as trastuzumab, a monoclonal antibody directed against HER2 |
| 25594009 | Consequently, there is an urgent need to identify novel drugs that can efficiently kill HER2(+) BC and/or potentiate the effect of existing anti-HER2 therapies |
| 25594009 | We performed a lenti-viral shRNA kinome screen on non-adherent mouse Her2/Neu tumorspheres and identified TBK1, a non-canonical IkappaB kinase (IKK), as the most potent target [1] |
| 25594009 | In addition, TBK1-II cooperated with lapatinib, a EGFR/HER2 inhibitor, to accelerate apoptosis in vitro and suppress tumor growth in a xenograft model of HER2(+) BC |
| 25594009 | Thus, TBK1/IKKepsilon inhibitors may improve treatment of HER2(+) BC in cooperation with anti-HER2 therapy |
| 25229978 | Acetylation-defective mutants of Ppargamma1 were associated with reduced lipid synthesis in ErbB2 overexpressing breast cancer cells |
| 24487029 | HER2(+) breast cancer is currently treated with chemotherapy plus anti-HER2 inhibitors |
| 24487029 | Therefore, there is an urgent need for new therapeutics that can target HER2(+) breast cancer and potentiate the effect of anti-HER2 inhibitors, in particular those that can target tumor-initiating cells (TIC) |
| 24487029 | Using tumorsphere formation as surrogate for TICs, we screened p53-mutant Her2/Neu(+) tumorsphere versus monolayer cells with a lentivirus short hairpin RNA kinome library |
| 24487029 | We identified kinases such as the mitogen-activated protein kinase and the TGFbetaR protein family, previously implicated in HER2(+) breast cancer, as well as autophagy factor ATG1/ULK1 and the noncanonical IkappaB kinase (IKK), TANK-binding kinase 1 (TBK1), which have not been previously linked to HER2(+) breast cancer |
| 24487029 | Knockdown of TBK1 or pharmacologic inhibition of TBK1 and the related protein, IKKepsilon, suppressed growth of both mouse and human HER2(+) breast cancer cells |
| 24487029 | In addition, TBK1/IKKepsilon inhibition cooperated with lapatinib, a HER2/EGFR1-targeted drug, to accelerate apoptosis and kill HER2(+) breast cancer cells both in culture and in xenografts |
| 24487029 | Our results suggest that patients with HER2(+) breast cancer may benefit from anti-TBK1/IKKepsilon plus anti-HER2 combination therapies and establish conditions that can be used to screen for additional TIC-specific inhibitors of HER2(+) breast cancer |
| 24074787 | Their distribution is highly linked to molecular tumor subtypes found in 26% of luminal tumors (17% of luminal A, 41% of luminal B), in 50% of HER2 amplified tumors, in 69% of molecular apocrine breast carcinomas and in 88% of basal-like carcinomas |
| 24000115 | In this study, we investigated the efficacy of some new synthetic derivatives of berberine, a phytochemical isolated from Barberry and other plants, to induce growth arrest of HER-2/neu overexpressing SK-BR-3 breast cancer cells |
| 24000115 | Furthermore, berberine, NAX012 and NAX014, all reduced both HER-2/neu expression and phosphorylation on tumor cells, the NAX014 compound showing the higher effectiveness |
| 24000115 | These results provide novel information on the mechanisms involved in the anticancer effects of berberine and demonstrate the greater effectiveness of NAX012 and NAX014 analogs in inducing apoptosis and cellular senescence in HER-2/neu overexpressing tumor cell lines |
| 23634980 | Activating mutations and senescence secretome: new insights into HER2 activation, drug sensitivity and metastatic progression |
| 23634980 | HER2 amplification and overexpression is observed in approximately 20% of breast cancers and is strongly associated with poor prognosis and therapeutic responsiveness to HER2 targeted agents |
| 23634980 | A recent study by Bose and colleagues suggests that another subset of breast cancer patients without HER2 amplification but with activating HER2 mutation might also benefit from existing HER2-targeted agents and the authors functionally characterize these somatic mutations in experimental models |
| 23634980 | In a second study on HER2-driven breast cancer, Angelini and colleagues investigate how the constitutively active, truncated carboxy-terminal fragment of HER2, p95HER2, promotes metastatic progression through non-cellautonomous secretion of factors from senescent cells |
| 23634980 | These new findings advance our understanding of HER2 biology in the context of HER2 activation as well as offer new insights into our understanding of drug sensitivity and metastatic progression |
| 23288917 | Constitutive HER2 signaling promotes breast cancer metastasis through cellular senescence |
| 23288917 | Here, we show that the expression in different breast epithelial cell lines of p95HER2, a constitutively active fragment of the tyrosine kinase receptor HER2, results in either increased proliferation or senescence |
| 23288917 | This secretory phenotype is not a mere consequence of the senescence status and requires continuous HER2 signaling to be maintained |
| 23178160 | Progestin drives breast cancer growth by inducing p21(CIP1) expression through the assembly of a transcriptional complex among Stat3, progesterone receptor and ErbB-2 |
| 23178160 | We found that the synthetic progestin medroxyprogesterone acetate (MPA) upregulates p21(CIP1) protein expression via c-Src, signal transducer and activator of transcription 3 (Stat3) and ErbB-2 phosphorylation |
| 23178160 | Notably, we also found that ErbB-2 nuclear function plays a key role in MPA-induction of p21(CIP1) expression |
| 23178160 | Interestingly, we determined that progestin drives p21(CIP1) transcriptional activation via a novel nonclassical transcriptional mechanism in which progesterone receptor is recruited along with Stat3 and ErbB-2 to a Stat3 binding site at p21(CIP1) promoter |
| 23178160 | Our findings revealed that ErbB-2 functions as a coactivator of Stat3 in progestin induction of p21(CIP1) transcriptional activation |
| 23178160 | Moreover, we provided evidence that Stat3 and nuclear ErbB-2 are key players in progestin-induced p21(CIP1) regulation |
| 22178194 | As a model system we used MCF-7 breast cancer cells with doxycycline-inducible expression of NeuT, an oncogenic ERBB2 variant |
| 21930937 | HER2 overcomes PTEN (loss)-induced senescence to cause aggressive prostate cancer |
| 21930937 | In this study, we show that patients who develop prostate tumors with low levels of PTEN and high levels of HER2/3 have a poor prognosis |
| 21930937 | This is functionally relevant, as targeting Her2 activation to the murine prostate cooperates with Pten loss and drives CaP progression |
| 21930937 | Taken together, these data suggest that stratification of CaP patients for HER2/3 and PTEN status could identify patients with aggressive CaP who may respond favorably to MEK inhibition |
| 21627565 | In the present study, we investigated the expression of human telomerase reverse transcriptase (hTERT) and TA and their regulation, as well as apoptotic rates and correlation with the presence of human epidermal growth factor receptor 2 (HER2), in irradiated tumour-derived breast cancer cells |
| 21627565 | MATERIALS AND METHODS: In 50 breast cancer tissue samples hTERT mRNA expression and TA were correlated with cell features (HER2, Estrogen and Progesterone Receptor status) |
| 21627565 | HER2 gene knockdown was performed using small interfering RNA technology |
| 21627565 | RESULTS: hTERT/TA were found increased only in irradiated HER2-positive cells, which were found to be more radioresistant, while HER2 knockdown led to hTERT/TA downregulation |
| 21627565 | HER2 was found to mediate hTERT expression through activation of Nuclear Factor-kappa B (NF-kappaB) and c-myc |
| 21627565 | CONCLUSIONS: The present study suggests that following irradiation, HER2 receptor activates hTERT/telomerase, increasing the breast cancer cells' survival potential, through sequential induction of transcription factors NF-kappaBeta and c-myc |
| 21297664 | Here, we investigated the role of Hsp72 in Her2 oncogene-induced neoplastic transformation and tumorigenesis |
| 21297664 | Expression of Her2 in untransformed MCF10A mammary epithelial cells caused transformation, as judged by foci formation in culture and tumorigenesis in xenografts |
| 21297664 | However, expression of Her2 in Hsp72-depleted cells failed to induce transformation |
| 21297664 | Further, we developed an animal model of Hsp72-dependent breast cancer associated with expression of Her2 |
| 21297664 | In young Hsp72 KO mice, expression of Her2 instead of mammary tissue hyperplasia led to suppression of duct development and blocked alveolar budding |
| 20622894 | Here, we show that HSF1 is required for the cell transformation and tumorigenesis induced by the human epidermal growth factor receptor-2 (HER2) oncogene responsible for aggressive breast tumors |
| 20622894 | Upon expression of HER2, untransformed human mammary epithelial MCF-10A cells underwent neoplastic transformation, formed foci in culture and tumors in nude mouse xenografts |
| 20622894 | However, expression of HER2 in MCF-10A cells with knockdown of HSF1 did not cause either foci formation or tumor growth in xenografts |
| 20585577 | Luminal, basal-like, "normal-like", and ERBB2+ subgroups were identified and were shown to have different prognoses |
| 19841470 | After having identified prosenescent and proapoptotic doses of epirubicin and rat MAb c-erbB2/Her-2/neu Ab-9 clone B10 (B10), an anti-erbB2 monoclonal antibody, we investigated the effects of the sequential treatment with prosenescent doses of both drugs on H9c2 cells and neonatal rat cardiomyocytes pretreated with or without the cardioprotective agent dexrazoxane |
| 19841470 | Data demonstrate that 1) the toxic effects of epirubicin mainly occur through NAD(P)H oxidase activation; 2) the erbB2 overexpression induced by epirubicin is a redox-sensitive mechanism largely dependent on NAD(P)H oxidase; 3) the loss of erbB2-related functions caused by B10 determines marginal cellular changes in untreated cells, but causes massive death by apoptosis in cells previously exposed to a prosenescent dose of epirubicin, 4) dexrazoxane promotes survival pathways, as demonstrated by the activation of Akt and the PI3K-dependent erbB2 overexpression; and 5) it also prevents epirubicin-induced senescence and renders epirubicin-treated cells more resistant to treatment with B10 |
| 17986575 | ER81 may mediate telomerase activation in telomerase-negative fibroblasts stimulated by oncogenes Her2/Neu, Ras, and Raf |
| 17100566 | The results may have two important implications for oncogene-blocking therapies: (i) downregulation of oncogenes, for instance HER2, MYC, RAS, RAF, BCR-ABL or WNT1, usually leads to a rapid tumor remission |
| 8893868 | Amplification and/or overexpression of the oncogenes epidermal growth factor receptor and erbB2 are associated with later stage disease |
| 8853900 | We show that forced expression of a number of cell cycle-regulatory genes, including erbB-2, v-ras, v-myc, B-myb, ld-1, and E2F-1, alone or in combinations, cannot induce terminally differentiated skeletal muscle cells (myotubes) to synthesize DNA |
| 8028398 | Cell aging of human diploid fibroblasts is associated with changes in responsiveness to epidermal growth factor and changes in HER-2 expression |
| 8028398 | Expression of the EGF receptor homologue HER-2 was also examined |
| 8028398 | The HER-2 mRNA level was significantly reduced in old cells |
| 8028398 | Moreover, HER-2 expression was stimulated by EGF addition in young cells but not in old cells |
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