Database for Annotation, Visualization and Integrated Discovery 2.1
National Institute of Allergy and Infectious Disease
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erb-b2 receptor tyrosine kinase 3(ERBB3) erb-b2 receptor tyrosine kinase 3(ERBB3) Related Genes Homo sapiens
GENERIF_SUMMARY AP-2gamma is important in the regulation of Erbb-3 expression in human mammary epithelial and lung fibroblast cells, Epidermal growth factor contains both positive and negative determinants for interaction with ErbB-2/ErbB-3 heterodimers, Role of the N-terminus of epidermal growth factor in binding studied by phage display., structure reveals a contact between domains II and IV that constrains the relative orientations of ligand-binding domains, Nrdp1/FLRF is a ubiquitin ligase promoting ubiquitination and degradation of this epidermal growth factor receptor family member, role of overexpression in lung cancer development in conjunction with erb-B-2 overexpression, the ErbB-3 affinity of a ligand determines whether it can form only ErbB-2/ErbB-3 complexes or also ErbB-3 homodimers., Activation of ErbB3 pathway may contribute to the development of dedifferentiated carcinomas, Expression of epidermal growth factor receptor, erbB2, and erbB3, but not erbB4, was detected throughout the epidermis. Labeling for erbB2 and erbB3 accentuated in upper spinous layers, These results suggest that ErbB3 expression alone does not uniquely confer IFN-alpha growth responsiveness, but instead may amplify proliferation rates in MM cells that have acquired atypical expression of this receptor., ErbB2/ErbB3 dimer functions as an oncogenic unit to drive breast tumor cell proliferation., ERBB2 and ERBB3 expression is inhibited by quercetin, resulting in decreased autophosphorylation and cell growth, Overexpression of ErbB3 is associated with transitional cell carcinoma of the bladder, ErbB3 is involved in IFN-alpha-induced proliferation of myeloma cells., heterodimer formation with heregulin regulates erbB2 receptor, This review summarizes evidence of defective expression of erbB3 in the prefrontal cortex of schizophrenic patients, implicating erbB3 involvement in the pathogenesis of schizophrenia., ErbB3 is an obligate heterodimerization partner because of its inability to homodimerize., before extracellular signal-regulated kinase activation and aquaporin synthesis, the membrane-bound prohormone neuregulin 1-beta is cleaved and binds to human epidermal growth factor receptor 3, calculated binding free energies between the N-SH2 domain of PI-3 kinase and P-peptides generated by erbb3 showed excellent qualitative agreement with SPR data with a correlation coefficient of 0.91, most of the ErbB3-ECD on the cell surface is apparently kept in an open conformation through oligomerization, ErbB3 proteins are promising targets for therapy, and siRNAs may be useful for this purpose., Potential of anti-HER3 antibodies for the therapy of breast cancer and other malignancies characterized by overexpression of HER3., Inhibition of HER2/HER3 signaling protects against pulmonary fibrosis and improves survival., Transcriptional activity of eztrogen receptor beta was altered in a manner similar to ERalpha by activation of ErbB2/ErbB3., Cell proliferation was increased when ErbB2 and ErbB3 were both overexpressed., the most notable changes consisted in the overexpression of ErbB3 by Schwann cells of nerves from Charcot-Marie-tooth disease type 1A patients, ERBB3 is the pivotal element of the Erbb pathway promoting tumorigenesis by heterodimerization with NEU or EGFR, but the NEU/EGFR dimer does not appear to play a significant role in prostate cancer, HER2 overexpression was the best single predictive marker, but combinations of HER3, HER2 markers provided additional predictive information., The high frequency of ErbB3 nuclear localization in hormone-refractory tissues indicates that ErbB3 warrants further study to understand its association with prostate cancer disease progression., HER3 and HER4 has been related to a favourable prognosis in bladder cancer., Muc4 potentiates neuregulin signaling by increasing the cell-surface populations of ErbB2 and ErbB3, ErbB3 has six binding sites for PI3K. All three Y-E-Y motifs contain a binding site for PI3K at the first tyrosine residue. 2 motifs contain a binding site for Grb2 at the second tyrosine., the neuregulin/ERBB3 signaling pathway is constitutively activated in clear cell sarcoma of soft tissue, Sox10-regulated overexpression of ErbB3 may be driving growth in pilocytic astrocytoma., failure to find genetic association suggests that the differential expression of ERBB3 in schizophrenia may be environmentally driven, or involve cis- or trans-acting genetic factors beyond the boundaries of the gene itself, enhanced signaling from the HER2/neu-HER3 pathway has a role in growth of tumors treated with fulvestrant in the presence of physiologic estradiol, Neuregulin 1-induced protein stability cascade involving USP8 and Nrdp1 mediates the down-regulation of ErbB3, there were no significant association between the polymorphisms or haplotypes of ERBB3 and schizophrenia; study shows that ERBB3 does not play a major role in conferring susceptibility to schizophrenia in the Japanese population, findings show that amplification of MET causes gefitinib resistance in lung cancer by driving ERBB3 (HER3)-dependent activation of PI3K, a pathway thought to be specific to EGFR/ERBB family receptors, HER3 signaling pathway plays an important role in the biological behavior of certain non-small cell lung cancers., Increased expression of erbB3 may play an additional role in non-small-cell lung carcinomas especially in female, nonsmoker, adenocarcinoma, and with EGFR gene mutation., Nuclear localization of ErbB-3 may aid prostate cancer cell survival during androgen ablation and progression of prostate cancer in bone., p45-sErbB3 may mediate the bidirectional interactions between prostate cancer cells and bone via osteonectin, These data suggest that the distinct topography of receptors and their docking partners modulates signaling activities., analysis of EGFR, HER2 and HER3 expression in esophageal primary tumours and corresponding metastases, Ligand-induced structural transitions in ERBB3 extracellular domains are reported., Lethal congenital contractural syndrome type 2 is caused by aberrant splicing of ERBB3, which leads to a predicted truncated protein., results demonstrate that Bmx is a critical downstream target of the constitutively active PI 3-kinase in PTEN-deficient PCa cells and further show that Bmx is recruited by the EGF receptor and ErbB3 and activated in response to their respective ligands, ErbB3 and ErbB4 genes play different roles in carcinogenesis and development, and relate to the reccurrence of carcinoma., ErbB-3 expression was associated with better prognosis in invasive ductal carcinomas of the breast., N-glycosylation controls ErbB signaling by various mechanisms., disruption of surface HSP90/HER-2 interaction leads to inhibition of heregulin-induced HER-2-HER-3 heterodimer formation, reduced HER-2 phosphorylation, and impaired downstream kinase signaling., Strong HER3 staining was found in 26.7% of both the primary tumors and the corresponding metastases., HER3 gene amplification showed a univariate negative impact on disease-free survival, In human uterine leiomyomas, ERBB3 were also overexpressed., the alpha6beta4 integrin strongly influence Akt phosphorylation through ErbB-3 protein regulation, Elevated EGFR, Her2, and Erbb3 phosphotyrosine is dependent on FGFR2; shRNA to Erbb3 resulted in a loss of proliferation in gastric neoplasms., HRG-induced activation of ErbB3 via EGFR promotes tumor growth and metastasis of melanoma cells, Her3 showed significantly increased expression in differentiated thyroid cancer and correlated with lymph node metastasis,tumor type,and higher N stage, The apparent correlation between higher sErbB3 levels and longer time to bone metastasis suggests that sErbB3 participates in progression in bone of prostate cancer., Datas show that transforming growth factor beta engages TACE and ErbB3 to activate phosphatidylinositol-3 kinase/Akt in ErbB2-overexpressing breast cancer and desensitizes cells to trastuzumab., inhibition of HER3 may be more clinically relevant than inhibition of EGFR in HER2-amplified breast cancer and adding pertuzumab to trastuzumab may augment therapeutic benefit by blocking HER2/HER3 signaling, Our results provide novel insights into the role of HER3 in melanoma and point out new possibilities for therapeutic intervention, Akt1 activation accelerates MMTV-c-ErbB2 mammary tumourigenesis in mice without activation of ErbB3, Patients with HER2 nonamplified and HER1 through HER3-negative tumors showed significantly increased relapse-free and overall survival rates when treated with epirubucin-CMF., Protein kinase A-mediated gating of neuregulin-dependent ErbB2-ErbB3 activation has a role in the synergistic action of cAMP on Schwann cell proliferation, These data support a role for EBP1 in the development of hormone-refractory prostate cancer., ERBB3 receptors are apparently segregated from ERBB2 receptors in their resting state, and both ligand-activated ERBB3 and ERBB2 do not share the same microenvironment as inactive ERBB3, HER3 and HER4 gene transcription is associated with better prognosis in high-risk early breast cancer., HER3 overexpression is strongly associated with tumor progression and poor prognosis of patients with gastric cancer, The biological function and clinical implications of HRG, HER-3 and HER-4 in breast cancers negative/low expression of HER-2 remain unclear, repression of MUC4 expression resulted in diminution of the phosphorylation of ErbB2 and ErbB3, expression of ErbB3 and ErbB4 may identify a colorectal cancer subgroup with stage II and III colorectal cancer at higher risk of recurrence., Results showed that 45.8% of typical carcinoid and 28.6% of atypical carcinoid tumors express EGFR, 100% of the tumors lack expression of ErbB2, and 100% have moderate to intense staining for ErbB3 and ErbB4., Current data relating to the prognostic significance of HER3 and 4 receptors, as well as their impact on the activity of HER-targeting therapies in patients with breast cancer., Data demonstrate a more stable binding of heregulin to cells co-expressing HER3 and HER2 than those expressing HER3 alone., Data show that aberrant expression of ErbB2, ErbB3 and ErbB4 in the two resistant cell lines, suggesting the existence of an autocrine loop leading to constitutive activation of MAPK and PI3K/Akt survival pathways., Non-small cell lung carcinoma brain metastases have some significant differences in HER family receptor-related abnormalities from primary lung tumors., Nuclear Y-box binding protein-1 is correlated with expression of HER2/ErbB2 and HER3/ErbB3 in non-small cell lung cancer., Results show that NRG1/ERBB3 signaling inhibits melanocyte (MC) maturation and promotes undifferentiated, migratory and proliferative cellular characteristics., HER3 mRNA was down-reg'd after stim'n with heregulin-beta1 and EGF in ovarian cancer cell lines either growth sensitive or growth resistant to pertuzumab. Pertuzumab reversed the down-reg'n and the magnitude of this corr'd with pertuzumab sensitivity., Heregulin might affect colon cancer growth by regulating VEGF secretion via the erbB3 signaling pathway through autocrine and paracrine mechanisms., Observed weak transactivation is uni-directional where stimulation of EGFR leads to HER3 activation whereas HER3 stimulation does not activate the EGFR., We investigated the ERBB3 gene given the putative functional nature of the gene and population heterogeneity between Asian and Caucasian. Scottish case and control samples were sequenced with four SNPs (rs705708 at intron 15., EGFR mutation combined with HER2/3 expression is a significant predictor for gefitinib efficacy on Chinese patients with advanced non-small cell lung cancer., These results suggest that P2Y(2)R activation in salivary gland cells promotes the formation of EGFR/ErbB3 heterodimers and metalloprotease-dependent neuregulin 1 release, resulting in the activation of both EGFR and ErbB3., Results suggest that trastuzumab resistance in breast cancer might be overcome by therapeutic strategies that jointly target erbB3, erbB2, and IGF-IR., HER-3 expression is correlated with better prognosis in neuroendocrine cancer, ErbB3 has a role in cell proliferation in ovarian cancer., ErbB3/HER3 intracellular domain is competent to bind ATP and catalyze autophosphorylation., erbB3 immunoreactivity was prominent in CD133-positive putative tumor stem cells., The study emphasizes the central role of EGFR in epidermal renewal and demonstrates that HRG-activated HER3 contributes to the outgrowth process of epidermis in vitro., observations suggest that PI3K mutants enhance HER2-mediated transformation by amplifying the HER3 ligand-induced signaling output of the ErbB network, Association of the polymorphisms of the ERBB3 and SH2B3 genes with type 1 diabetes, Observations point to a model of CRPC development in which progression of PCa to castration resistance is associated with the inability of AR to transcriptionally regulate Nrdp1, and predict that inhibition of ErbB3 during AW may impair CRPC development., Over-expression of ErbB2 by transient transfection resulted in partial separation of the receptors by relocalization of ErbB2, but not ErbB3, to the apical surface, as shown by biotinylation of the apical or basolateral surfaces, Data show that the brain metastases over-expressed one or more members of the HER family and in particular HER3 was significantly over-expressed relative to matched primary tumors., Data show that knockdown of integrin alphav and erbB3 by small-interfering RNAs significantly inhibited cell migration induced by HRG., Post-transcriptional mechanisms contribute to the suppression of the ErbB3 negative regulator protein Nrdp1 in mammary tumors., Data show that ErbB3 appears to be critically involved in EGFR signaling as evidenced by its profound effect on cellular proliferation and its ability to influence response to EGFR-targeted therapy., results show that ZNF217 regulates ErbB3 expression, Results indicate that ERBB3 plays a critical role in determining APC function and potentially T1D pathogenesis., direct NRG1-integrin interaction mediates integrin-ErbB3 cross-talk and that alpha6beta4 plays a major role in NRG-ErbB3 signaling in these cancer cells., HER3 mRNA levels may be a biomarker for active ligand-induced HER2-HER3 signaling, with low HER3 mRNA levels correlated with clinical benefit from the HER2-HER3 dimerization inhibitor pertuzumab., Data show that integrin alpha(6)beta(4) interacts with ErbB3 but not with ErbB1, ErbB2 or ErbB4, and enhances the heregulin-induced, ErbB3/ErbB2 heterodimer-mediated DNA synthesis, but not cell motility, in A549 cells., Data show that blockade of amphiregulin suppressed the activities of EGFR, HER3, and Akt and the expression of amphiregulin itself., quantification of EGFR and HER3 mRNA expression in pretreatment biopsies may be useful to identify patients who are at risk of developing metastases, The data demonstrate that sclerostin functions in part, by modulating the activity of erbB-3., HER3 seems not to be of such interest for radionuclide therapy in colorectal carcinoma due to mainly expression in the cytoplasm, HER receptor family plays an important role in embryonic development and in pathogenesis and progression of neuroblastic tumors., The constitutive activation of ERBB3-dependent signaling via the NRG1/ERBB3 autocrine loop plays a crucial role in the regulation of cell motility and invasion, which contribute to intrahepatic metastasis and early recurrence of hepatocellular carcinoma., HER overexpression orchestrates broad changes in the tumor microenvironment by altering the secretion of a diverse variety of biologically active proteins., therapeutic inhibitors of HER3 should be used in combination with HER2 inhibitors and PI3K pathway inhibitors in patients with HER2- and PI3K-dependent cancers, We found a significant correlation of HER2 with human epidermal growth factor receptor 3 (HER3/erbB3), epidermal growth factor receptor 1 (EGFR/HER1/erbB1) and urokinase plasminogen receptor (uPAR) in breast cancer tissues., 148 Penile squamous cell carcinoma were microarrayed and immunostained for phosphorylated EGFR (pEGFR), HER2, HER3, HER4, phosphorylated Akt (pAkt), Akt1 and PTEN proteins., ARF6 can affect ErbB-3 nuclear localization in prostate cancer cells., HER3 is frequently localized solely in the cell nuclei in UM and as such it predicts a more favorable overall survival., Data demonstrate that Nrdp1 preferentially associates with the nascent form of ErbB3 to accelerate its degradation, and that the two proteins colocalize at the endoplasmic reticulum., demonstrate the therapeutic potential of this approach by showing that bivalent NRG (NN) can bias signaling in HER3-expressing cancer cells, resulting in some cases in decreased migration, inhibited proliferation, and increased apoptosis, In situ detection of HER2 and HER2, HER3 expression was significantly related to worse survival in gastric cancer., Results indicate that stimulation of the early metastatic steps of motility and invasion by ErbB3 requires activation of the PI3-kinase pathway by the ErbB3 receptor., DARPP-32 increases interactions between epidermal growth factor receptor and ERBB3 to promote tumor resistance to gefitinib., Stromal (Cancer-Associated Fibroblasts)CAF-secreted NRG-1 stimulates ErbB3/AKT signalling and promotes pancreatic cancer cell tumourigenesis, providing a mechanism that may contribute to PDAC resistance to anti-EGFR therapy., Membranous Her3 expression is strongly associated with poor prognosis of patients with head and neck squamous cell carcinoma., sERBB3 may have a role in portal-vein invasion and extrahepatic metastasis of hepatocellular carcinoma, erbB3 recruitment of insulin receptor substrate 1 modulates insulin-like growth factor receptor signalling in oestrogen receptor-positive breast cancer cell lines, The anti-ErbB3 antibodies modulate the growth rate of cancer cells of different origins., Findings show that the bispecific antibody MM-111 forms a trimeric complex with ErbB2 and ErbB3, effectively inhibiting ErbB3 signaling and showing antitumor activity in preclinical models that is dependent on ErbB2 overexpression., ErbB3(80 kDa) increases the transcription of proliferative genes even when the cytoplasmic pathways are not activated., Report the interplay of HER2/HER3/PI3K and EGFR/HER2/PLC-gamma1 signalling in breast cancer cell migration and dissemination., results indicate that downregulation of ErbB3 induced by Wnt3a contributes to Wnt3a-induced early osteoblast differentiation of MSCs through increased canonical Wnt/beta-catenin signaling and decreased Src signaling, Signaling via the HER2/HER3 pathway in breast carcinoma cell lines may lead to enhanced natural killer cell (NKG2D)-histocompatibility class I-related chains A/B (MICA/B) recognition by NK cells and T cells., Immunoreactivity for erbB1 was strong and that for erbB2 and 3 was moderate, while that for erbB4 was faint in nasal mucosa chronic rhinitis., ErbB3 is endocytosed in the absence of added ligand., Data show that miR-22 inhibited the expression of ErbB3 through post-transcriptional regulation via binding to ErbB3 3' untranslated regions (3'-UTR)., Mutation of this amino acid led to increased ERBB receptor activation and upregulation of the ERBB3/PI3K/AKT signaling pathway, which was no longer responsive to MEK inhibition, This study revealed that the previously described up-regulation of EGFR and down-regulation of ERBB4 occurred in all analyzed renal cell carcinoma types, whereas down-regulation of ERBB2 and LRIG1 was only present in clear cell renal cell carcinoma., HER3 expression was significantly associated with patients who have post-menopausal high tumour grade progesterone receptor negativity., Higher order complexes of nonoverexpressed ERBB receptors are an integral and qualitatively distinct part of normal ERBB2/ERBB3 signaling., Binding of L1CAM to erbB enhances its response to neuregulins., Correlation of HER2, p95HER2 and HER3 expression and treatment outcome of lapatinib plus capecitabine in her2-positive metastatic breast cancer., the highly regulated nature of HER3 and its role as a dynamic signalling hub linking HER family oncogenes with downstream PI3K/Akt pathway signalling., In ER-positive breast cancer, correlations were found in the expression of activated HER-receptors (pHER1, pHER2, pHER3), indicating a potential role of HER1 and HER3 in the activation of HER2. HER3 expression was not associated with prognosis., We observed the reaction kinetics between fluorescently labeled single HRG molecules and ErbB3/B4 on the surfaces of MCF-7 human breast cancer cells., intracellular domains play a crucial role in HER3's function as an allosteric activator and its role in downstream signaling, ErbB3 might be considered as a biomarker for major depressive disorder (MDD). ErbB3 but not fibroblast growth factor receptor (Fgfr)1 mRNA levels are reduced in leukocytes of MDD patients compared to healthy subjects., In extrahepatic cholangiocarcinoma HER3 overexpression is correlated with decreased patient survival, suggesting that HER3 constitutes a prognostic factor., The -276 C/T polymorphism was associated with the risk of lung cancer in a recessive model of never-smokers. Interestingly, the T allele conferred significantly lower promoter activity by 32% and 33% than the C allele in H2009 and H358 cell lines., Our findings demonstrate that HER2 and HER3 co-expression induces IL8 autocrine signaling, leading to the invasion of mammary cells., Low expression of ERBB3 is associated with neuroblastoma progression., Results suggest a possible participation of erbB1-4 and claudin-1 in tissue remodelling in chronic hypertrophic rhinitis., These findings reveal that ERBB2 and ERBB3 expression is regulated by ROS via miR-199a and miR-125b downregulation and DNA hypermethylation., the neuregulin 1-HER axis is a key mediator of hyperglycemic memory effects in breast cancer, A direct correlation between basal HER3 expression and sensitivity to elisidepsin is observed; moreover, modulation of HER3 expression levels in different cancer cell lines alters their sensitivities to the drug, HER3 pathway activation is associated with lung cancer., The present data suggest that ErbB2, ErbB3, and ErbB4 genes may have a role in bladder cancer tumorigenesis., Data suggest that ErbB receptors (ERBB2, ERBB3, and ERBB4) are expressed in most endometrial cancers; expression of ErbB receptors appears to be related to poor prognosis; dismal outcomes correlate with cancers positive for all three ErbB receptors., high-level expression of HRG is associated with constitutive activation of HER3 in SCCHN and thus defines an actionable biomarker for interventions targeting HER3., an NRG1-ERBB3-ERBB2 signaling unit operates in melanoma cells where it promotes growth and survival., the suppressive role of Necl-2 in the HRG-induced ErbB2/ErbB3 signaling is regulated by miR-199a at least through the reduction of the ST6GAL1-catalyzed sialylation of Necl-2, ErbB3 is involved in bone tumor growth and ErbB3 expression in human osteosarcoma correlates with tumor grade, upregulation of ERBB3 is involved in melanoma adapting to RAF/MEK inhibitors through FOXD3, results indicate that Necl-4 serves as a tumor suppressor by inhibiting the ErbB2/ErbB3 signaling and hemidesmosome disassembly, beta4 integrin rs8669 genotyping may help to identify a subgroup of HER-3-negative, K-RAS wild-type colorectal cancer patients who are more likely to benefit from anti-EGFR treatment., This review article surveyed human cancers and identified recurrent somatic ERBB3 mutations and show that these mutations are transforming., Altogether the results indicate that pertuzumab can be a valuable therapeutic agent not only in cancers overexpressing ErbB2 but also in cancers co-expressing ErbB2 and ErbB3, EGFR interacts with Grb2 in both constitutive and EGF-dependent manners, whereas the HER3-Grb2 interaction requires the heteromerization of EGFR and HER3., Data indicate that Lrig3 opposes Lrig1 negative regulatory action and enhances ErbB receptors ERBB2, ERBB3 and ERBB4 stability., Asymmetric kinase dimer formation is crucial for the activation of oncogenic EGFRvIII but not for ERBB3 phosphorylation., Heregulin binding was prevented by RG7116 at concentrations more than 1 nmol/L as was nearly complete inhibition of HER3 heterodimerization., results suggest that IGF-1R and HER3 differentially regulate trastuzumab resistance and could be promising targets for trastuzumab therapy in ovarian cancer, ERBB3 is a clear-cut marker of a ganglioneuroblastoma/ganglioneuroma-like expression profile., Carboxyl group footprinting mass spectrometry and molecular dynamics identify key interactions in the HER2-HER3 receptor tyrosine kinase interface., Studies indicate high percentage of HER3 positivity in patients with pancreatic cancer, and a high prevalence of PI3K and AKT activation as well, suggesting responsiveness to erlotinib and validating the idea of targeting therapy., Our data suggest that HRG-beta1 and ErbB3 induce epithelial-mesenchymal transition, cancer cell migration and invasion in breast cancer cells, These analyses identified a bipartite region of 34 (B) and 27 (B) amino acids in length that conferred the majority of HER3's transactivation potential., constructed an integrated mathematical model of HER activation and trafficking. Studied HER phosphorylation and abundance data collected in a panel of human mammary epithelial cells expressing varying levels of EGFR/HER1, HER2 and HER3., In tumours from postmenopausal women harbouring normal HER2 gene copy numbers, we found HER2 and HER4, but HER3 levels in particular, to be elevated compared to controls, HER-3 overexpression is associated with breast cancer., Analysis of HER3 expression in tumor samples indicated that radiation treatment activated HER3 in vivo and that U3-1287/AMG888 could abrogate this activation., Upregulation of ErbB3 in luminal breast cancer cells promotes growth, survival, and resistance to fulvestrant., all pairings of the EGF receptor, ErbB2, and ErbB3 form ligand-independent dimers/oligomers., MTK1 was identified in the HER2/HER3-HRG mediated extracellular acidification and cell migration pathway in breast cancer cells., An heregulin-EGFR-HER3 autocrine signaling axis can mediate acquired lapatinib resistance in HER2+ breast cancer models., HER-3 has become a focus of concern in the HER family and has gained significant attention in the search for cancer treatment., the N-glycan-deleted mutant of sErbB3 suppresses heregulin signaling via ErbB3-containing heterodimers more effectively than the wild type., EBRR3 p.Val104Met and p.Val104Leu mutations that are recurrent and might be targeted in cancer therapy is rarely mutated in hematologic neoplasia and may not be therapeutically targeted in these neoplasia, Data indicate that the blockade of IGF-I receptor (IGF-IR) and ErbB3 receptor (ErbB3) survival pathways and downstream resistance mechanisms was achieved with MM-141., HER3 expression in the tumour was an independent prognostic factor, where a high HER3 expression was associated with worse clinical outcome. There was a correlation in HER3 expression between primary tumour and corresponding lymph node metastases., Patients who had negative HER3 staining (62.4%) had a better progression-free survival., Studies suggest that concomitant inhibition of erbB3 receptor is required to overcome the resistance and to effectively treat cancers., A high MUC1 expression was associated with a favourable prognosis in patients with bladder cancer when the expression of HER3 was also high. This suggests an involvement of HER3 in MUC1 function in bladder cancer., Coiled-coil domain deletion abrogates Nrdp1 oligomerization and suppresses Nrdp1 but not ErbB3 ubiquitination and degradation., Her3 promotes proliferation, survival and migration of human gastric cancer mediated by PI3K/AKT signaling pathway, Results demonstrated that NEDD4 is a novel interaction partner of HER3 and the C-terminal tail of HER3 interacts with the WW domains of NEDD4., Antagonism of EGFR and HER3 enhances the response to inhibitors of the PI3K-Akt pathway in triple-negative breast cancer., Affinity-purified bispecific Affibody molecules, targeting HER2 and HER3., the ErbB3/4 ligand heregulin (HRG) reduced both ErbB2 and ErbB3 mRNA and protein levels in human breast cancer cell lines., We show for the first time the presence of HER2/HER3 heterodimers and the loss of p21 expression in HER2+ breast cancer predicts a significantly poorer outcome when submitted to adjuvant trastuzumab, Depletion of either flotillin-1 or flotillin-2 resulted in downregulation of ErbB3 and a selective reduction of ErbB2-ErbB3 receptor complexes., ErbB3, ErbB4, and MET showed marked expression in 76%, 98%, and 96% of ovarian carcinoma cases., These data support the concept that activation of ERBB family members is sufficient to bypass dependency on FGFR3 and suggest that concurrent inhibition of these two pathways may be desirable when targeting FGFR3-dependent cancers., This study confirmed presence of somatic mutations of ERBB3 in gastric cancers (GC) and colorectal cancers (CRC) and increased intensity of pERBB3, an activated ERBB3, in GC and CRC, and that such increased intensity was accompanied by ERBB3 mutations., Data show that proto-oncogene protein ERBB3 knockdown resulted in cell cycle arrest and activation of Bak and Bax-dependent apoptosis., MET, HER3, IGF1R, and INSR pathways activation represent novel mechanism underlying lapatinib unresponsiveness in HER2+ gastric cancer. Combination strategy may be recommended in treating patients with HER2+ gastric cancer with these pathways activation, HER2/HER3 co-overexpression is significantly associated with impaired survival from diagnosis of metastatic disease in patients with HER2-positive metastatic breast cancer., Findings suggest that deficient HER3 expression plays an important role in gefitinib sensitivity in poorly-differentiated colorectal cancer cells., miRNA-450b-3p as a new tumor repressor which downregulation with concurrent overexpression of HER3 may serve as a prognostic biomarker for poor overall survival in breast cancer patients., Overexpression and gene amplification of HER3 was found in biliary tract carcinomas., Additive impact of HER2-/PTK6-RNAi on interactions with HER3 or IGF-1R leads to reduced breast cancer progression, Findings provide clues regarding the role of the miR-143/145 cluster as a tumor suppressor in breast cancer through the inhibition of ERBB3 translation., NTS/NTSR1 complex enhances breast tumor aggressiveness via EGFR/HER2/HER3 pathway., Neurotensin and its receptor NTSR1 causes EGFR, HER2 and HER3 over-expression and their autocrine/paracrine activation in lung adenocarcinomas, confirming responsiveness to erlotinib., HER3 knock down decreases cell proliferation preferentially in PIK3CA kinase domain mutation (H1047R) cells., Her2/Her3 and Met/Her3 were verified in human GC., REVIEW in regulation of HER3 signaling in cancer, Phosphorylated ErbB1-4 and heregulin contribute to poorer patient prognosis in CRC. This heregulin-ErbB family member autocrine loop may be a candidate for targeted treatment of CRC., Cancer-associated HER3 mutations enhanced the allosteric activator function of HER3 by redesigning local interactions at the dimerization interface., Data show that the combination of PI3 kinase inhibitors with ErbB receptors HER2/HER3 targeting antibodies may constitute a promising therapeutic strategy for prostate cancer., ErbB2 and ErbB3 homodimers are endocytosis deficient owing to the lack of endocytic codes. Interestingly, EGFR-ErbB2 or EGFR-ErbB3 heterodimers are also endocytosis deficient, GAB adaptor proteins play a role in ERBB3-independent activation of the PI3K pathway by mutant EGFR in EGFR-mutant human cell lines., For selected miRNAs, namely miR-149, miR-148b, miR-326, and miR-520a-3p, we demonstrate the simultaneous downregulation of the ErbB3 receptor and multiple downstream signaling molecules., A major conformational change of HER3 during its activation is induced by a complex sequential HRG1beta docking mode., HER3 is correlated with the malignant biological behaviour of gastric cancer. Expression of HER3 is a significant predictor of poor survival in GC., Although not an independent prognostic factor for overall survival, HER3 overexpression was associated with several favourable prognostic clinicopathologic parameters in colorectal cancer, activates YAP and stimulates cancer cell growth. Knockdown of ERBB3 or HBEGF eliminates YAP effects on cell growth and transformation, The ability of EBP1 to activate ErbB2 signaling pathways results in increased lapatinib sensitivity., Data (including data from SZ95 sebocyte cell line) suggest sebocytes abundantly express EGFR (epidermal growth factor receptor) with lower levels of ERBB2 and ERBB3; expression of these receptors appears coordinated with lipogenesis in specific ways., Using various assessment methods and patient populations, our results revealed that there was no significant correlation between ErbB3 expression and breast cancer survival. Meta-analysis., Data show that proto-oncogene protein HER-2 overexpression occurs in only 8% of patients with colorectal cancer (CRLM) but with 75% of cases proto-oncogene protein HER-3 is frequently overexpressed in CRLM., the EGFR and ErbB-3 heterodimerization, regarded as the origin of intracellular signaling pathways, was investigated., The aim of the study was to evaluate the prognostic ability of the transcriptional profiling of the HER family genes in early breast cancer., Dual blockade of EGFR and HER3 may enhance the targeted disruption of HER family signaling in these cancers both by blocking parallel and overlapping signaling pathways and potentially blocking the emergence of resistance., HER3/MUC4 oncogenic signaling aggravates the tumorigenic phenotypes of pancreatic cancer cells, findings show that the local 3D tumor microenvironment can trigger reprograming and switching of ErbB family members and thereby influence ErbB3-driven tumor growth, Heregulin-ErbB3-Driven Tumor Growth Persists in PI3 Kinase Mutant Cancer Cells, Expression of total HER2, total HER3 were significantly elevated in HPV(+) HNSCC., ERa-dependent expression of LRIG1 dampens ErbB3 signaling in luminal breast cancer cells, and by blocking ERa activity with fulvestrant, LRIG1 is decreased thus permitting ErbB3 accumulation, enhanced ErbB3 signaling to cell survival pathways, both ErbB-2 and ErbB-3 receptors are expressed in colon cancer stem cells and NRG-1beta plays an important role in sustaining proliferation of both wild-type and BRAF-V600E mutated cells, Data indicate that high heregulin mRNA and high HER3 protein levels are independently correlated with poor overall survival in patients with oropharyngeal squamous cell carcinoma., these studies support the rationale to target the NRG1-ErbB3-ErbB2 axis as a novel treatment strategy in a subset of cutaneous melanomas., SNP in HER2 codon 655 and investigation of HER2 and HER3 expression could be helpful to outline the prognosis for patients with lung adenocarcinoma., Findings suggest that triple therapy directed against BRAF/MEK/ErbB3 may be able to provide durable control of BRAF mutated metastatic melanoma., Data indicate that increased expression of erbB3 plays a pivotal role in activating downstream PI-3K/Akt pathway and promoting erbB2-driven mammary/breast tumorigenesis., neuregulin 1 promotes compensatory ErbB3 receptor signaling in mutant BRAF melanoma, Using a new pyrosequencing assay, this study uncovers an E332E mutation affecting HER3 in retroperitoneal leiomyosarcoma clinical samples., Data show that cotreatment with anti-ERBB3 proto-oncogene protein antibody seribantumab and letrozole had increased antitumor activity., ERBB3 Positively Correlates with Intestinal Stem Cell Markers but Marks a Distinct Non Proliferative Cell Population in Colorectal Cancer., Results demonstrate that acquired resistance of colorectal tumour cells to treatment with anti-EGFR mAb ICR62 is accompanied by an increased level of cell surface EGFR, and upregulation of phosphorylated HER-2 and HER-3 proteins., Authors show experimental evidence for an ErbB3 gain-of-function point mutation located in the C-lobe asymmetric dimerization interface, which shows enhanced phosphorylation at low ligand dose associated with increased kinase activity., critical pathophysiologic event in the evolution of HER2-amplified cancers is the loss of the input signals that normally drive TORC2 signaling, repositioning it under Akt dependency, and fundamentally altering the role of HER3, Study shows that ERBB3 is a novel regulator of beta-cell apoptosis and found rs2292239 strongly correlated with residual b-cell function and metabolic control in children with type 1 diabetes., findings newly identify a physiological function of the NRG1-ErbB2-ErbB3 axis in trophoblast survival during human placental development., BRCA1-associated DCIS did not express ER, PR or HER2, while most BRCA2-associated DCIS did express ER and PR. BRCA1- as well as BRCA2-associated DCIS had expression of HER3 and C-MET, our results suggest that HER3 over-expression may be associated with worse overall survival in gastric cancers, Data suggest that NDRG1 down-regulates expression and activation of HER1/EGFR, HER2/ERBB2, and HER3/ERBB3 in response to epidermal growth factor (EGF) ligand in pancreatic/colonic neoplasm cells., NRG1 promotes the proliferation and migration of coronary artery smooth muscle cells by enhancing the phosphorylation of ErbB2, ErbB3 and ErbB4., HER2/HER3 interaction and increased expression was linked to risk for poor outcome in lung cancer patients., ErbB3 nuclear translocation is a common event in proliferating tissues., High EGFR expression was an independent risk factor for shorter overall survival (OS), whereas high HER3 expression was associated with a borderline significant trend towards a longer OS., while transcript and protein levels of EGFR and ErbB2 were up-regulated or unaffected, respectively, hepatitis c virus induced a substantial reduction of ErbB3 and ErbB4 expression., HPV 16 E2 can modulate ErbB-3 by interacting with Nrdp-1, which is involved in the regulation of this receptor, via ubiquitination and degradation., Data indicate that clathrin-mediated endocytosis of proto-oncogene protein erbB-3 (ErbB3) is depending on epsin-1., measurements comprising the receptors EGFR, ERBB3 (HER3), and the cyclin-dependent kinase inhibitor p27 (CDKN1B) was found to accurately predict dependence on PI3K/AKT vs. MAPK/ERK signaling axes in HER2+ cancers, HER Family Protein Expression in a Greek Population with Gastric Cancer. A Retrospective Hellenic Cooperative Oncology Group Study, Expression and Prognostic Significance of Human Epidermal Growth Factor Receptors 1, 2 and 3 in Periampullary Adenocarcinoma,
OMIM_DISEASE Lethal congenital contractural syndrome 2,
SP_COMMENT catalytic activity:ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate., disease:Defects in ERBB3 are the cause of lethal congenital contracture syndrome type 2 (LCCS2) [MIM:607598]; also called Israeli Bedouin multiple contracture syndrome type A. LCCS2 is an autosomal recessive neurogenic form of a neonatally lethal arthrogryposis that is associated with atrophy of the anterior horn of the spinal cord. The LCCS2 syndrome is characterized by multiple joint contractures, anterior horn atrophy in the spinal cord, and a unique feature of a markedly distended urinary bladder. The phenotype suggests a spinal cord neuropathic etiology., disease:Overexpressed in a subset of human mammary tumors., domain:The cytoplasmic part of the receptor may interact with the SH2 or SH3 domains of many signal-transducing proteins., function:Binds and is activated by neuregulins and NTAK., PTM:Ligand-binding increases phosphorylation on tyrosine residues and promotes its association with the p85 subunit of phosphatidylinositol 3-kinase., similarity:Belongs to the protein kinase superfamily. Tyr protein kinase family. EGF receptor subfamily., similarity:Contains 1 protein kinase domain., subunit:Heterodimer with each of the other ERBB receptors (Potential). Interacts with CSPG5, PA2G4 and MUC1., tissue specificity:Epithelial tissues and brain.,