ArticleOncogene2013
Truncated p110 ERBB2 induces mammary epithelial cell migration, invasion and orthotopic xenograft formation, and is associated with loss of phosphorylated STAT5.
Article in Oncogene, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
31 citing papers in PubMed, 43 citations in OpenAlex.
- Metabolic hallmarks of trastuzumab resistance.Expert opinion on therapeutic targets · 2025Review
- p95HER2, a truncated form of the HER2 oncoprotein, drives an immunosuppressive program in HER2Nature cancer · 2025Article
- Trastuzumab resistance in HER2-positive breast cancer: Mechanisms, emerging biomarkers and targeting agents.Frontiers in oncology · 2022Review
- Heterogeneous delivery across the blood-brain barrier limits the efficacy of an EGFR-targeting antibody drug conjugate in glioblastoma.Neuro-oncology · 2021Article
- Selective ERBB2 and BCL2 Inhibition Is Synergistic for Mitochondrial-Mediated Apoptosis in MDS and AML Cells.Molecular cancer research : MCR · 2021Article
- Separation-encoded microparticles for single-cell western blotting.Lab on a chip · 2020Article
- Article
- Oncogenic activity of poly (ADP-ribose) glycohydrolase.Oncogene · 2019Article
- Single-cell mobility shift electrophoresis reports protein localization to the cell membrane.The Analyst · 2019Article
- High p95HER2/HER2 Ratio Associated With Poor Outcome in Trastuzumab-Treated HER2-Positive Metastatic Breast Cancer NCCTG N0337 and NCCTG 98-32-52 (Alliance).Clinical cancer research : an official journal of the American Association for Cancer Research · 2018Article
- Electrophoretic cytopathology resolves ERBB2 forms with single-cell resolution.NPJ precision oncology · 2018Article
- Modeling the process of human tumorigenesis.Nature communications · 2017Review
- ErbB2 regulates autophagic flux to modulate the proteostasis of APP-CTFs in Alzheimer's disease.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- A clinically feasible multiplex proteomic immunoassay as a novel functional diagnostic for pancreatic ductal adenocarcinoma.Oncotarget · 2017Article
- Profiling protein expression in circulating tumour cells using microfluidic western blotting.Nature communications · 2017Observational
- Adaptor proteins NUMB and NUMBL promote cell cycle withdrawal by targeting ERBB2 for degradation.The Journal of clinical investigation · 2017Article
- Low EGFR/MET ratio is associated with resistance to EGFR inhibitors in non-small cell lung cancer.Oncotarget · 2015Article
- Quantitative HER2 and p95HER2 levels in primary breast cancers and matched brain metastases.Neuro-oncology · 2015Article
- Binding-induced, turn-on fluorescence of the EGFR/ERBB kinase inhibitor, lapatinib.Organic & biomolecular chemistry · 2015Article
- Article
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
Truncated-ERBB2 isoforms (t-ERBB2s), resulting from receptor proteolysis or alternative translation of the ERBB2 mRNA, exist in a subset of human breast tumors. t-ERBB2s lack the receptor extracellular domain targeted by therapeutic anti-ERBB2 antibodies and antibody-drug conjugates, including trastuzumab, trastuzumab-DM1 and pertuzumab. In clinical studies, expression of t-ERBB2 in breast tumors correlates with metastasis as well as trastuzumab resistance. By using a novel immuno-microarray method, we detect a significant t-ERBB2 fraction in 18 of 31 (58%) of immunohistochemistry (IHC)3+ ERBB2+ human tumor specimens, and further show that t-ERBB2 isoforms are phosphorylated in a subset of IHC3+ samples (10 of 31, 32%). We investigated t-ERBB2 biological activity via engineered expression of full-length and truncated ERBB2 isoforms in human mammary epithelial cells (HMECs), including HMEC and MCF10A cells. Expression of p110 t-ERBB2, but not p95m (m=membrane, also 648CTF) or intracellular ERBB2s, significantly enhanced cell migration and invasion in multiple cell types. In addition, only expression of the p110 isoform led to human breast epithelial cell (HMLE) xenograft formation in vivo. Expression of t-ERBB2s did not result in hyperactivation of the phosphoinositide kinase-3/AKT or mitogen-activated protein kinase signaling pathways in these cells; rather, phosphoproteomic array profiling revealed attenuation of phosphorylated signal transducer and activator of transcription 5 (STAT5) in p110-t-ERBB2-expressing cells compared to controls. Short hairpin-mediated silencing of STAT5 phenocopied p110-t-ERBB2-driven cell migration and invasion, while expression of constitutively active STAT5 reversed these effects. Thus, we provide novel evidence that (1) expression of p110 t-ERBB2 is sufficient for full transformation of HMEC, yielding in vivo xenograft formation, and (2) truncated p110 t-ERBB2 expression is associated with decreased phosphorylation of STAT5.
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