Affinage

Showing ERBB2 — HER2 is a alias.

ERBB2

Receptor tyrosine-protein kinase erbB-2 · UniProt P04626

Length
1255 aa
Mass
137.9 kDa
Annotated
2026-06-09
100 papers in source corpus 17 papers cited in narrative 16 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/7 claims corpus-supported (86%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ERBB2/HER2 is a ligand-less receptor tyrosine kinase that functions as the preferred heterodimerization partner for ErbB1, ErbB3, and ErbB4, generating signaling-competent complexes that slow ligand dissociation, evade lysosomal degradation by recycling to the cell surface, and strongly engage MAPK and PI3K survival/mitogenic pathways, driving cyclin-D/CDK activity and chemoresistance (PMID:11156523). Downstream, HER2 activates the PI3K/AKT axis to confer drug resistance (PMID:20664599) and constitutively drives HSF1 (Ser326) phosphorylation via PI3K-AKT-mTOR to sustain HSP90 chaperone activity and stabilize oncogenic clients (PMID:24384723). Its activity is held in check by negative regulators: the phosphatase PTPN13 dephosphorylates the HER2 signaling domain in a growth-factor-induced feedback loop, and tumor-derived PTPN13 mutations elevate HER2 oncogenic and invasive potential (PMID:17982484), while calmodulin binds HER2 in a Ca2+-dependent manner to modulate its phosphorylation and downstream ERK/AKT signaling (PMID:15080792). Receptor stability and trafficking are governed by septin complexes at the plasma membrane, which shield HER2 from ubiquitylation, endocytosis, and cathepsin-B-dependent lysosomal degradation (PMID:27048593), and HER2 ubiquitination/internalization governs the delivery and efficacy of anti-HER2 antibody-drug conjugates (PMID:32213539). Recurrent transmembrane and juxtamembrane mutations (e.g., G660D) are activating by stabilizing the active dimer interface and promoting asymmetric kinase dimerization, and remain sensitive to anti-HER2 antibodies and kinase inhibitors (PMID:30449325). Upon apoptotic stimulation, caspases cleave the HER2 cytoplasmic tail to release fragments bearing a functional BH3-like domain that translocate to mitochondria and trigger Bcl-xL-suppressible cytochrome c release and caspase-dependent apoptosis, acting analogously to Bad (PMID:18420586). HER2 signaling is also physiologically essential in adult cardiomyocytes, where its deletion causes dilated cardiomyopathy (PMID:12072561, PMID:14749494).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1992 Medium

    Established that HER2 protein levels are dynamically down-regulated by EGFR ligands, an early indication that receptor abundance is actively controlled rather than fixed.

    Evidence ELISA and surface RIA quantification of HER2 protein and mRNA after EGF/TGF-alpha treatment in ovarian and mammary carcinoma cells

    PMID:1355758

    Open questions at the time
    • Mechanism of protein down-regulation not resolved (mRNA effect insufficient)
    • No link to ubiquitylation or trafficking machinery established at this stage
  2. 2000 High

    Defined HER2's core mechanism as a ligand-less heterodimerization partner that biases trafficking toward recycling and amplifies MAPK/PI3K survival signaling, explaining its oncogenic potency.

    Evidence Review synthesizing receptor internalization assays, signaling activation studies, and cell cycle analyses

    PMID:11156523

    Open questions at the time
    • Does not identify the regulators controlling dimer choice
    • Mechanistic basis of recycling vs degradation not molecularly resolved
  3. 2001 Medium

    Identified PDZ-domain partners that spatially organize HER2, linking its C-terminal tail to basolateral localization and receptor clustering.

    Evidence Co-IP, pulldown, and domain-mapping with ERBIN and PICK1; subcellular localization studies

    PMID:11278603

    Open questions at the time
    • Functional consequence of clustering for signaling output not quantified
    • Single-lab interaction data
  4. 2002 High

    Demonstrated a physiological, non-oncogenic requirement for HER2 in adult cardiomyocytes, establishing the basis for cardiac vulnerability to HER2-directed therapy.

    Evidence Cardiomyocyte-specific Cre-loxP conditional knockout with cardiac phenotyping; replicated independently

    PMID:12072561 PMID:14749494

    Open questions at the time
    • Ligand/dimer partner driving cardiac HER2 signaling not defined here
    • Downstream effectors in cardiomyocytes not mapped
  5. 2004 Medium

    Showed HER2 is a Ca2+-dependent calmodulin-binding protein whose phosphorylation and ERK/AKT output depend on CaM, adding a calcium-sensing layer to receptor regulation.

    Evidence CaM-agarose pulldown, overlay assay, Ca2+-dependent chromatography, and W7 pharmacological inhibition in cells

    PMID:15080792

    Open questions at the time
    • CaM-binding site on HER2 not mapped
    • W7 effects not exclusive to CaM-HER2 axis
    • Single lab
  6. 2007 Medium

    Identified PTPN13 as a negative-feedback phosphatase for HER2 and linked its loss-of-function mutations to enhanced HER2 oncogenicity, establishing dephosphorylation as a tumor-suppressive brake.

    Evidence siRNA phosphatase library screen, PTPN13 knockdown, activity assays with tumor-derived mutants, invasion assays

    PMID:17982484

    Open questions at the time
    • Direct phosphosite specificity on HER2 not enumerated
    • Single lab
  7. 2008 High

    Revealed a pro-apoptotic dimension of HER2: caspase cleavage of its cytoplasmic tail liberates BH3-like fragments that engage the mitochondrial apoptotic pathway, recasting the receptor as a Bad-like effector under apoptotic stress.

    Evidence In vitro caspase cleavage, mutagenesis of cleavage sites, mitochondrial translocation and cytochrome c release assays, Bcl-xL co-IP

    PMID:18420586

    Open questions at the time
    • Physiological contexts triggering this cleavage in vivo unclear
    • Relative contribution vs canonical apoptotic regulators not quantified
  8. 2010 Medium

    Established the HER2/PI3K-AKT axis as a node for paclitaxel resistance and tissue-specific oncogenic outputs (prolactin induction in prolactinoma), connecting HER2 to therapy resistance and endocrine tumor biology.

    Evidence siRNA knockdown with dominant-negative AKT rescue in endometrial cancer; constitutively active HER2 with lapatinib vs gefitinib in prolactinoma models

    PMID:20664599 PMID:21106881

    Open questions at the time
    • Effector specificity downstream of AKT not fully resolved
    • Tissue-specific transcriptional mechanisms not mapped
  9. 2012 Medium

    Uncovered a nuclear HER2 function via macroH2A1.2 interaction at the HER2 promoter, defining a feed-forward loop sustaining HER2 expression and tumorigenicity.

    Evidence Co-IP, ChIP, macro-domain mutagenesis, knockdown and overexpression, tumorigenicity assays

    PMID:22589551

    Open questions at the time
    • How HER2 reaches the nucleus not defined
    • Single lab
  10. 2014 Medium

    Connected HER2 overexpression to constitutive HSF1 activation and HSP90 client stabilization, explaining how HER2 maintains a proteostatic environment supporting oncogenic clients.

    Evidence Lapatinib/CP724.714/siRNA HER2 inhibition, phospho-HSF1(Ser326) blotting, client stability assays, in vivo ErbB2 tumor model, PI3K rescue

    PMID:24384723

    Open questions at the time
    • Direct kinase phosphorylating Ser326-HSF1 downstream of HER2 not identified
    • Single lab
  11. 2016 High

    Identified septin complexes as plasma-membrane protectors of HER2, resolving a long-standing question of how surface HER2 evades ubiquitylation and lysosomal degradation independently of HSP90.

    Evidence Co-IP/MS, septin-2 siRNA, forchlorfenuron disruption, ubiquitylation and lysosomal inhibitor assays, surface HER2 quantification

    PMID:27048593

    Open questions at the time
    • E3 ligase mediating HER2 ubiquitylation upon septin loss not identified
    • Septin-HER2 contact interface not structurally defined
  12. 2018 High

    Mechanistically explained activating transmembrane/juxtamembrane mutations as stabilizers of the active dimer interface and asymmetric kinase dimerization, defining a druggable mutational class.

    Evidence Saturation mutagenesis, structural modeling of TMD/JMD interfaces, kinase activity assays, inhibitor treatment, clinical validation

    PMID:30449325

    Open questions at the time
    • Quantitative signaling differences among individual mutants not fully resolved
    • Resistance trajectories under inhibitor pressure not addressed here
  13. 2019 Medium

    Validated HER2 kinase-domain mutations as activating in MSI colorectal cancer and showed differential dependence on the active conformation, refining inhibitor-class selection.

    Evidence Functional treatment of ERBB2-mutant CRC lines with reversible/irreversible inhibitors, antibodies, and siRNA; viability assays

    PMID:26001389

    Open questions at the time
    • Structural basis of conformational dependency for these specific mutants not solved
    • Single lab
  14. 2020 High

    Demonstrated that HER2 ubiquitination and endocytosis—not mere overexpression—govern antibody-drug conjugate delivery, and that pan-HER inhibitors enhance ADC efficacy by promoting internalization, translating receptor trafficking biology into therapy.

    Evidence Ubiquitination and internalization assays, viability assays in cell lines and PDX, clinical trial of T-DM1 in ERBB2-altered lung cancer

    PMID:32213539

    Open questions at the time
    • E3 ligase coupling inhibitor treatment to ubiquitylation not pinpointed
    • Predictive biomarkers of internalization capacity not defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • The integration of opposing trafficking forces (septin protection vs ubiquitin-driven endocytosis) and the molecular identity of the E3 ligase(s) controlling HER2 degradation remain unresolved, despite their therapeutic centrality to ADC efficacy.
  • HER2 E3 ubiquitin ligase not identified in the corpus
  • Mechanism coupling kinase inhibition to receptor ubiquitylation unknown
  • How nuclear, mitochondrial, and surface pools of HER2 are partitioned is unclear

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 2 GO:0060089 molecular transducer activity 1 GO:0060090 molecular adaptor activity 1
Localization
GO:0005886 plasma membrane 2 GO:0005634 nucleus 1 GO:0005739 mitochondrion 1
Pathway
R-HSA-162582 Signal Transduction 2 R-HSA-1643685 Disease 2 R-HSA-5653656 Vesicle-mediated transport 2 R-HSA-5357801 Programmed Cell Death 1 R-HSA-8953897 Cellular responses to stimuli 1
Partners
CALM1EGFRERBB3ERBB4ERBINMACROH2A1PICK1PTPN13

Evidence

Reading pass · 16 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 ErbB2 acts as a ligand-less signaling subunit that heterodimerizes with ErbB1, ErbB3, and ErbB4; ErbB2-containing heterodimers decrease the rate of ligand dissociation, internalize slowly, avoid lysosomal degradation by returning to the cell surface, and strongly recruit MAPK and PI3K survival/mitogenic pathways. ErbB2 overexpression upregulates active cyclin-D/CDK complexes and p21waf1, linking it to cell cycle dysregulation and chemoresistance. Review synthesizing biochemical and cell-biological experiments (receptor internalization assays, signaling pathway activation studies, cell cycle analyses) Oncogene High 11156523
2002 Conditional cardiomyocyte-specific deletion of ErbB2 in mice causes severe dilated cardiomyopathy with cardiac dysfunction, demonstrating that ErbB2 signaling in the heart (where it is enriched in T-tubules) is essential for adult cardiac function. Cre-loxP conditional knockout in ventricular cardiomyocytes; cardiac phenotyping including chamber dilation, wall thinning, and contractility measurements Proceedings of the National Academy of Sciences of the United States of America High 12072561 14749494
2001 ERBB2/HER2 interacts with PDZ-domain proteins ERBIN and PICK1 through its C-terminal PDZ-binding sequence. ERBIN localizes ErbB2 to the basolateral epithelium, while PICK1 is involved in receptor clustering. ERBIN and PICK1 bind ErbB2 through distinct mechanisms that are regulated in cells. Co-immunoprecipitation, pulldown assays, domain-mapping experiments, subcellular localization studies The Journal of biological chemistry Medium 11278603
2004 ErbB2/Neu/HER2 is a calmodulin (CaM)-binding protein; it binds CaM in a Ca2+-dependent manner. CaM antagonist W7 down-regulates ErbB2 phosphorylation and inhibits downstream ERK1/2 and Akt/PKB phosphorylation, demonstrating that CaM regulates ErbB2 activity and signaling in vivo. CaM-agarose pulldown, Ca2+-dependent affinity chromatography, biotinylated CaM overlay assay on immunoprecipitated ErbB2, pharmacological inhibition with W7 in live cells, Western blotting for phospho-ERK and phospho-Akt The Biochemical journal Medium 15080792
2007 Protein tyrosine phosphatase PTPN13 negatively regulates Her2/ErbB2 by dephosphorylating the Her2 signaling domain. Growth factor-induced phosphorylation of PTPN13 is required for Her2 dephosphorylation (negative feedback). Tumor-derived PTPN13 mutations reduce its phosphatase activity, elevating Her2 oncogenic potential and cancer cell invasiveness. siRNA phosphatase library screen, PTPN13 knockdown with phosphorylation readout, PTPN13 phosphatase activity assays with tumor-derived mutants, invasion assays Oncogene Medium 17982484
2008 Caspases cleave the cytoplasmic tail of HER-2 at Asp1016/Asp1019 to release a ~47-kDa product, which is further cleaved at Asp1125 into a 22-kDa (proteasome-degraded) and predicted 25-kDa fragment. Both 47- and 25-kDa cleavage products translocate to mitochondria, release cytochrome c via a Bcl-xL-suppressible mechanism, and induce caspase-dependent apoptosis through a functional BH3-like domain, acting analogously to Bad. In vitro caspase cleavage assays, site-directed mutagenesis of caspase cleavage sites, mitochondrial fractionation/translocation assays, cytochrome c release assay, co-immunoprecipitation with Bcl-xL, apoptosis readouts The Journal of biological chemistry High 18420586
2014 Overexpressed HER2/ErbB2 constitutively activates heat-shock factor 1 (HSF1) via the PI3K-AKT-mTOR axis, which in turn sustains HSP90 chaperone activity. This stabilizes HSP90 clients including MIF, AKT, mutant p53, and HSF1 itself. Pharmacological or siRNA-mediated HER2 inhibition blocks pSer326-HSF1, destabilizes these clients, and suppresses tumor proliferation in vitro and in vivo. HER2 inhibition by lapatinib, CP724.714, or siRNA knockdown; Western blotting for phospho-HSF1 (Ser326); HSP90 client stability assays; in vivo mouse ErbB2 tumor model; heat-shock stress experiments; pathway rescue with PI3K inhibitors Cell death & disease Medium 24384723
2012 The atypical histone macroH2A1.2 (but not macroH2A1.1) interacts with nuclear HER-2 in cancer cells via its evolutionarily conserved macro domain (specifically requiring the -EIS- trinucleotide insert). This interaction promotes HER-2 expression and tumorigenicity; inhibition of HER-2 kinase activity diminishes macroH2A1 expression. Chromatin immunoprecipitation shows macroH2A1.2 enrichment at the HER-2 promoter. Co-immunoprecipitation, ChIP, domain-mapping mutagenesis, siRNA knockdown, overexpression studies, tumorigenicity assays The Journal of biological chemistry Medium 22589551
2016 Septins form complexes with ErbB2 at the plasma membrane (identified by co-immunoprecipitation/MS), protecting ErbB2 from ubiquitylation, endocytosis and lysosomal degradation. Knockdown of septin-2 or pharmacological disruption of septin oligomerization (forchlorfenuron) increases ErbB2 ubiquitylation, triggers its endocytosis and lysosomal degradation via cathepsin B, and reduces surface ErbB2 levels. This mechanism is distinct from and additive with Hsp90-mediated ErbB2 stabilization. Co-immunoprecipitation followed by mass spectrometry, septin-2 siRNA knockdown, forchlorfenuron treatment, ubiquitylation assays, lysosomal inhibitor experiments, surface ErbB2 quantification The Biochemical journal High 27048593
2018 Recurrent HER2 transmembrane domain (TMD) and juxtamembrane domain (JMD) mutations (G660D, R678Q, E693K, Q709L) are activating. Structural modeling and saturation mutagenesis show that TMD/JMD mutations improve the active dimer interface or stabilize an activating conformation. G660D employs asymmetric kinase dimerization for activation and signaling. Anti-HER2 antibodies and small-molecule kinase inhibitors block the activity of these mutants. Saturation mutagenesis screen, structural modeling of TMD/JMD dimer interfaces, kinase activity assays, inhibitor treatment of mutant-expressing cells, clinical case validation Cancer cell High 30449325
2020 HER2 ubiquitination and internalization (endocytosis), rather than simple overexpression, are the key mechanisms underlying intracellular delivery and efficacy of anti-HER2 antibody-drug conjugates (T-DM1 and T-DXd) in lung cancer. Co-treatment with irreversible pan-HER inhibitors enhances HER2 ubiquitination and consequent ADC internalization and efficacy. Ubiquitination assays, internalization/endocytosis assays, cell viability assays in cell lines and patient-derived xenograft models, clinical trial (T-DM1 in ERBB2-amplified/mutant lung cancers) Cancer discovery High 32213539
2006 In ADPKD epithelia, apical localization of EGFR complexes is associated with heterodimerization of EGFR (HER-1) with HER-2, while basolateral localization in normal adult epithelia is associated with EGFR homodimers. Specific inhibition of HER-2 (by AG825 or ErbB2 siRNA) reverses the migration defect of ADPKD epithelial cells and inhibits cyst development in PKD1 heterozygous mice, with p38MAPK acting downstream of HER-2 stimulation. Co-immunoprecipitation (heterodimerization), specific HER-2 inhibitor AG825, ErbB2 siRNA knockdown, cell migration bioassay, p38MAPK inhibition, in vivo PKD1 mouse model Biochimica et biophysica acta Medium 16797938
2010 In prolactinoma cells, constitutively active HER2/ErbB2 potently induces prolactin (PRL) mRNA and secretion (~250-fold and ~100-fold respectively) and increases cell proliferation. Lapatinib (dual EGFR/HER2 TKI) blocks receptor signaling and suppresses PRL expression more effectively than gefitinib (EGFR-only), demonstrating a HER2-specific mechanism. Stable transfection of constitutively active HER2 into GH3 cells, mRNA and secretion measurements, lapatinib vs. gefitinib treatment, soft agar colony formation, oral lapatinib in rat prolactinoma models, cultured human prolactinoma cells Molecular endocrinology (Baltimore, Md.) Medium 21106881
2010 In endometrial cancer cells, HER-2 activates the PI3K/AKT pathway (HER-2/PI3K-AKT axis): siRNA-based knockdown of HER-2 significantly reduces phospho-AKT. This axis confers resistance to paclitaxel; HER-2 knockdown increases paclitaxel sensitivity, and this sensitization is cancelled by dominant-negative AKT, confirming AKT as the mediating node. siRNA knockdown of HER-2, Western blotting for p-AKT, dominant-negative AKT rescue experiment, paclitaxel cytotoxicity assays British journal of cancer Medium 20664599
1992 EGF (and TGF-α) treatment of ovarian and mammary carcinoma cells significantly reduces HER-2 protein expression at the cell surface and total cellular level. In OVCAR-3 cells, EGF reduces HER-2 mRNA levels, but this effect is not observed in HER-2-overexpressing lines, suggesting that mRNA down-regulation is not the sole mechanism. ELISA for total HER-2 protein, living-cell RIA for surface HER-2, mRNA analysis, dose-response experiments with EGF and TGF-α International journal of cancer Medium 1355758
2019 In HER2-mutant (L755S, V842I) MSI colorectal cancer cell lines, irreversible pan-HER inhibitors are superior to reversible inhibitors or individual antibodies, functionally validating these ERBB2 mutations as activating and demonstrating differential dependency on the kinase active conformation. Functional treatment of ERBB2-mutated CRC cell lines with reversible/irreversible HER inhibitors, EGFR antibodies, trastuzumab, and siRNA-mediated ERBB2 knockdown; viability assays Gut Medium 26001389

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 Molecular mechanisms underlying ErbB2/HER2 action in breast cancer. Oncogene 464 11156523
2004 HER-2 gene amplification can be acquired as breast cancer progresses. Proceedings of the National Academy of Sciences of the United States of America 410 15194824
2002 Conditional mutation of the ErbB2 (HER2) receptor in cardiomyocytes leads to dilated cardiomyopathy. Proceedings of the National Academy of Sciences of the United States of America 375 12072561
2000 Overexpression of ErbB2 in cancer and ErbB2-targeting strategies. Oncogene 354 11156524
2015 ErbB2/HER2-Specific NK Cells for Targeted Therapy of Glioblastoma. Journal of the National Cancer Institute 319 26640245
2020 HER2-Mediated Internalization of Cytotoxic Agents in ERBB2 Amplified or Mutant Lung Cancers. Cancer discovery 240 32213539
2007 Augmented HER-2 specific immunity during treatment with trastuzumab and chemotherapy. Clinical cancer research : an official journal of the American Association for Cancer Research 180 17785568
2004 HER-2, gp100, and MAGE-1 are expressed in human glioblastoma and recognized by cytotoxic T cells. Cancer research 165 15256472
2004 Essential roles of Her2/erbB2 in cardiac development and function. Recent progress in hormone research 161 14749494
2008 HER-2 and topoisomerase II as predictors of response to chemotherapy. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 151 18258981
2017 Intrinsic Subtype Switching and Acquired ERBB2/HER2 Amplifications and Mutations in Breast Cancer Brain Metastases. JAMA oncology 143 27926948
2014 The Mysterious Ways of ErbB2/HER2 Trafficking. Membranes 143 25102001
2018 Actionable Activating Oncogenic ERBB2/HER2 Transmembrane and Juxtamembrane Domain Mutations. Cancer cell 139 30449325
2001 Overexpression of HER-2 as a resistance mechanism to hormonal therapy for breast cancer. Endocrine-related cancer 139 11566610
2010 Estrogen and HER-2 receptor discordance between primary breast cancer and metastasis. The oncologist 137 21041379
2018 EGFR and MET Amplifications Determine Response to HER2 Inhibition in ERBB2-Amplified Esophagogastric Cancer. Cancer discovery 135 30463996
2007 Dual inhibition of ErbB1 (EGFR/HER1) and ErbB2 (HER2/neu). European journal of cancer (Oxford, England : 1990) 135 17208435
2006 uPAR and HER-2 gene status in individual breast cancer cells from blood and tissues. Proceedings of the National Academy of Sciences of the United States of America 128 17079488
2020 HER2-Enriched Subtype and ERBB2 Expression in HER2-Positive Breast Cancer Treated with Dual HER2 Blockade. Journal of the National Cancer Institute 126 31037288
2022 Quantitative measurement of HER2 expression to subclassify ERBB2 unamplified breast cancer. Laboratory investigation; a journal of technical methods and pathology 123 35595825
2008 ERBB3/HER3 and ERBB2/HER2 duet in mammary development and breast cancer. Journal of mammary gland biology and neoplasia 121 18454306
2019 Plasma HER2 (ERBB2) Copy Number Predicts Response to HER2-targeted Therapy in Metastatic Colorectal Cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 119 30808777
2002 HER-2 profiling and targeting in prostate carcinoma. Cancer 115 11920466
2003 The clinical evaluation of HER-2 status: which test to use? The Journal of pathology 109 12635130
2017 CD73 Promotes Resistance to HER2/ErbB2 Antibody Therapy. Cancer research 103 28855210
2008 Imaging of HER-2 overexpression in tumors for guiding therapy. Current pharmaceutical design 103 18991715
2009 HER-2 signaling and inhibition in breast cancer. Current cancer drug targets 99 19442060
2016 HER-2 Positive Breast Cancer - a Mini-Review. Asian Pacific journal of cancer prevention : APJCP 90 27221828
2003 erbB-2 (HER-2) and breast cancer progression. Applied immunohistochemistry & molecular morphology : AIMM 86 12966347
2003 HER-2 and TOP2A coamplification in urinary bladder cancer. International journal of cancer 86 14566826
2001 The ERBB2/HER2 receptor differentially interacts with ERBIN and PICK1 PSD-95/DLG/ZO-1 domain proteins. The Journal of biological chemistry 82 11278603
2014 HER2/ErbB2 activates HSF1 and thereby controls HSP90 clients including MIF in HER2-overexpressing breast cancer. Cell death & disease 79 24384723
2015 Activating ERBB2/HER2 mutations indicate susceptibility to pan-HER inhibitors in Lynch and Lynch-like colorectal cancer. Gut 67 26001389
2004 Antitumor activity of HER-2 inhibitors. Cancer letters 67 16051028
2019 HER2/neu (ERBB2) expression and gene amplification correlates with better survival in esophageal adenocarcinoma. BMC cancer 60 30621632
2007 Protein tyrosine phosphatase PTPN13 negatively regulates Her2/ErbB2 malignant signaling. Oncogene 60 17982484
2010 HER2/ErbB2 receptor signaling in rat and human prolactinoma cells: strategy for targeted prolactinoma therapy. Molecular endocrinology (Baltimore, Md.) 56 21106881
2006 HER-2 and NF-kappaB as the targets for therapy-resistant breast cancer. Anticancer research 56 17201139
2015 Expression of COX-2 and HER-2 in colorectal cancer and their correlation. World journal of gastroenterology 54 26034355
2006 Inhibition of HER-2(neu/ErbB2) restores normal function and structure to polycystic kidney disease (PKD) epithelia. Biochimica et biophysica acta 54 16797938
2023 Convection-enhanced delivery of nanoencapsulated gene locoregionally yielding ErbB2/Her2-specific CAR-macrophages for brainstem glioma immunotherapy. Journal of nanobiotechnology 52 36805678
2006 Simultaneous amplification of HER-2 (ERBB2) and topoisomerase IIalpha (TOP2A) genes--molecular basis for combination chemotherapy in cancer. Current cancer drug targets 52 17100565
2007 HER2 therapy. HER2 (ERBB2): functional diversity from structurally conserved building blocks. Breast cancer research : BCR 51 17274834
2005 Identification and validation of novel ERBB2 (HER2, NEU) targets including genes involved in angiogenesis. International journal of cancer 50 15609325
2019 Detection of ERBB2 Amplification by Next-Generation Sequencing Predicts HER2 Expression in Colorectal Carcinoma. American journal of clinical pathology 48 31115453
2011 When tumor suppressor TGFβ meets the HER2 (ERBB2) oncogene. Journal of mammary gland biology and neoplasia 48 21590373
2010 Expression of Her-2 in carcinomas of the esophagus. The American journal of surgical pathology 48 21107094
2009 Stemming resistance to HER-2 targeted therapy. Journal of mammary gland biology and neoplasia 48 19259796
2009 Beyond trastuzumab: overcoming resistance to targeted HER-2 therapy in breast cancer. Current cancer drug targets 48 19275756
2018 Aberrant miRNAs expressed in HER-2 negative breast cancers patient. Journal of experimental & clinical cancer research : CR 44 30342533
2007 EGFR and HER-2 antagonists in breast cancer. Anticancer research 42 17593621
2010 An Immunohistochemical study of HER-2 expression in feline mammary tumours. Journal of comparative pathology 41 20880546
2012 The atypical histone macroH2A1.2 interacts with HER-2 protein in cancer cells. The Journal of biological chemistry 39 22589551
2018 Intratumoral heterogeneity of ERBB2 amplification and HER2 expression in micropapillary urothelial carcinoma. Human pathology 37 29601842
2013 EGFR, KRAS, BRAF, and HER-2 molecular status in brain metastases from 77 NSCLC patients. Cancer medicine 36 23930206
2004 The ErbB2/Neu/HER2 receptor is a new calmodulin-binding protein. The Biochemical journal 36 15080792
2019 Reduction of Global H3K27me3 Enhances HER2/ErbB2 Targeted Therapy. Cell reports 35 31597089
2008 Caspase cleavage of HER-2 releases a Bad-like cell death effector. The Journal of biological chemistry 35 18420586
2017 Quantifying HER-2 expression on circulating tumor cells by ACCEPT. PloS one 34 29084234
2008 EGFR, HER-2 and COX-2 levels in colorectal cancer. Histopathology 32 19102009
2015 Measurement of Domain-Specific HER2 (ERBB2) Expression May Classify Benefit From Trastuzumab in Breast Cancer. Journal of the National Cancer Institute 31 25991002
2006 HER-2 (c-erbB-2) test update: present status and problems. Breast cancer (Tokyo, Japan) 30 16929116
2023 Development of Electrochemical Immunosensors for HER-1 and HER-2 Analysis in Serum for Breast Cancer Patients. Biosensors 29 36979567
2019 Assessment of ERBB2/HER2 Status in HER2-Equivocal Breast Cancers by FISH and 2013/2014 ASCO-CAP Guidelines. JAMA oncology 29 30520947
2017 Expression of Hormone Receptors and HER-2 in Benign and Malignant Salivary Gland Tumors. Head and neck pathology 29 28681314
2007 HER-2, TOP2A and chromosome 17 alterations in breast cancer. Pathology oncology research : POR 29 17922046
2020 Targeted lapatinib anti-HER2/ErbB2 therapy resistance in breast cancer: opportunities to overcome a difficult problem. Cancer drug resistance (Alhambra, Calif.) 28 35582612
2011 The expression of HER-2 in extramammary Paget's disease. Bioscience trends 28 21914949
2021 Recent Advances in Systemic Treatments for HER-2 Positive Advanced Gastric Cancer. OncoTargets and therapy 27 34285507
2016 Dendrimer antibody conjugate to target and image HER-2 overexpressing cancer cells. Oncotarget 27 27144519
2008 HER-2 positive breast cancer: what else beyond trastuzumab-based therapy? Anti-cancer agents in medicinal chemistry 27 18537532
2008 The tyrosine kinase receptor HER2 (erbB-2): from oncogenesis to adipogenesis. Journal of cellular biochemistry 27 18814184
2005 HER-2: a biomarker at the crossroads of breast cancer immunotherapy and molecular medicine. Journal of cellular physiology 27 15887236
2005 The erbB2/HER2/neu receptor polymorphism Ile655Val and breast cancer risk. Pharmacogenetics and genomics 26 15970791
2000 HER-2/neu (erbB-2) and the cell cycle. Seminars in oncology 25 11236025
2021 HER-2 Amplification in Uterine Serous Carcinoma and Serous Endometrial Intraepithelial Carcinoma. The American journal of surgical pathology 24 33739786
2006 Controversies in the assessment of HER-2: more questions than answers. Advances in anatomic pathology 24 16998320
2015 HER-2 and HER-3 expression in liver metastases of patients with colorectal cancer. Oncotarget 23 25915155
2009 The role of topoisomerase IIalpha and HER-2 in predicting sensitivity to anthracyclines in breast cancer patients. Cancer treatment reviews 23 19758759
2001 Update on HER-2 as a target for cancer therapy: herceptin in the clinical setting. Breast cancer research : BCR 23 11737889
2008 DNA vaccination controls Her-2+ tumors that are refractory to targeted therapies. Cancer research 22 18794138
2019 Mechanism of trastuzumab resistance caused by HER-2 mutation in breast carcinomas. Cancer management and research 21 31308740
2004 Her-2 expression in cutaneous eccrine and apocrine neoplasms. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 21 14631375
2013 HER-2 gene amplification in human breast cancer without concurrent HER-2 over-expression. SpringerPlus 20 24102037
1997 p53 and HER-2 alterations in renal cell carcinoma. Urology 20 9338750
2023 Immunotherapy for HER-2 positive breast cancer. Frontiers in oncology 19 37007133
2016 Septin oligomerization regulates persistent expression of ErbB2/HER2 in gastric cancer cells. The Biochemical journal 19 27048593
2001 Inhibitors of HER2/neu (erbB-2) signal transduction. Seminars in oncology 19 11774203
2024 HER-2 positive gastric cancer: Current targeted treatments. International journal of biological macromolecules 18 38906351
2022 Recent advances in biosensor devices for HER-2 cancer biomarker detection. Analytical methods : advancing methods and applications 18 35318477
2018 HER-2 Immunohistochemical Expression in Bone Sarcomas: A New Hope for Osteosarcoma Patients. Open access Macedonian journal of medical sciences 18 30337965
2010 Expression of HER-2 affects patient survival and paclitaxel sensitivity in endometrial cancer. British journal of cancer 18 20664599
2023 ErbB2 (HER2)-CAR-NK-92 cells for enhanced immunotherapy of metastatic fusion-driven alveolar rhabdomyosarcoma. Frontiers in immunology 17 37662907
2021 [Clinical pathological expert consensus on HER-2 testing in urothelial carcinoma in China]. Zhonghua zhong liu za zhi [Chinese journal of oncology] 17 34695889
2008 Her-2 DNA versus cell vaccine: immunogenicity and anti-tumor activity. Cancer immunology, immunotherapy : CII 17 18836716
2019 Combined targeting of HER-2 and HER-3 represents a promising therapeutic strategy in colorectal cancer. BMC cancer 16 31488078
2019 HER2 gene (ERBB2) amplification is a rare event in non-liver-fluke associated cholangiocarcinogenesis. BMC cancer 16 31805897
2019 HER2 gene (ERBB2) amplification is a low-frequency driver with potential predictive value in gallbladder carcinoma. Virchows Archiv : an international journal of pathology 16 31838585
2014 HER-2 overexpression and survival in colorectal cancer: a meta-analysis. Journal of Zhejiang University. Science. B 16 24903996
1992 Epidermal growth factor reduces HER-2 protein level in human ovarian carcinoma cells. International journal of cancer 16 1355758

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