ArticleMolecular biology of the cell2004
Endocytosis and sorting of ErbB2 and the site of action of cancer therapeutics trastuzumab and geldanamycin.
Article in Molecular biology of the cell, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 237 papers.
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Who cites it
237 citing papers in PubMed, 487 citations in OpenAlex.
- Clinical cancer research : an official journal of the American Association for Cancer Research · 2017Trial
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- Impact of Trastuzumab and Pertuzumab on HER2 Localization and the Estrogen Receptor Cistrome in ER+/HER2+ Breast Cancer.bioRxiv : the preprint server for biology · 2026Article
- Intracellular Nanopharmacology of Trastuzumab Deruxtecan Reveals Lysosome-Centered Organelle Vulnerabilities in HER2-Positive Breast Cancer Cells.ACS nano medicine · 2026Article
- Targeting EGFR Endocytosis and Signaling for Cancer Drug Delivery and Cancer Treatment.Cancers · 2026Review
- Drug resistance to antibody-drug conjugates: mechanisms, challenges, and perspectives.Cancer biology & medicine · 2026Review
- Antibody-Drug Conjugates Targeting Resistance-Associated Signaling Pathways: Recent Advances and Future Perspectives.International journal of molecular sciences · 2026Review
- HER3 upregulation reduces DS-8201 sensitivity in HER2-positive tumor cells by ATR/CHK1/FoxO1 signaling cascade.Acta pharmacologica Sinica · 2026Article
- Bispecific antibody-drug conjugates: a modular blueprint for next-generation cancer therapeutics.Archives of pharmacal research · 2026Review
- Heat shock proteins at the crossroads of endosomal trafficking pathways.Cell biology and toxicology · 2025Review
- Mechanisms of resistance to antibody-drug conjugates in cancer: molecular barriers and pharmacological solutions.Cancer chemotherapy and pharmacology · 2025Review
- Unveiling the molecular and immunological drivers of antibody-drug conjugates in cancer treatment.Nature reviews. Cancer · 2025Review
- Hijacking Extracellular Targeted Protein Degrader-Drug Conjugates for Enhanced Drug Delivery.Journal of the American Chemical Society · 2025Article
- Enhanced HER2 internalization by clathrin-dependent endocytosis in non-small cell lung cancer positive for HER2 mutations.British journal of cancer · 2025Article
- The Autophagy Inhibitor Bafilomycin Inhibits Antibody-Dependent Natural Killer Cell-Mediated Killing of Breast Carcinoma Cells.International journal of molecular sciences · 2025Article
- Low-density lipoprotein receptor-targeting chimeras for membrane protein degradation and enhanced drug delivery.bioRxiv : the preprint server for biology · 2025Article
- Tumor-specific cytosol-penetrating antibodies for antigen- and TME-dependent intracellular cargo delivery.Molecular therapy. Oncology · 2025Article
- Measurement of specific and nonspecific tissue uptake of antibodies in tumor by SPECT imaging and nonlinear compartmental modeling.EJNMMI research · 2025Article
- Resistance to antibody-drug conjugates: A review.Acta pharmaceutica Sinica. B · 2025Review
- A trafficking regulatory subnetwork governs αScience advances · 2024Article
177 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
ErbB2 is a transmembrane tyrosine kinase whose surface overexpression is linked to tumorigenesis and poor prognosis in breast cancer patients. Two models have emerged that account for the high surface distribution of ErbB2. In one model, the surface pool is dynamic and governed by a balance between endocytosis and recycling, whereas in the other it is retained, static, and excluded from endocytosis. These models have contrasting implications for how ErbB2 exerts its biological function and how cancer therapies might down-regulate surface ErbB2, such as the antibody trastuzumab (Herceptin) or the Hsp90 inhibitor geldanamycin. Little is known, however, about how these treatments affect ErbB2 endocytic trafficking. To investigate this issue, we examined breast carcinoma cells by immunofluorescence and quantitative immunoelectron microscopy and developed imaging and trafficking kinetics assays using cell surface fluorescence quenching. Surprisingly, trastuzumab does not influence ErbB2 distribution but instead recycles passively with internalized ErbB2. By contrast, geldanamycin down-regulates surface ErbB2 through improved degradative sorting in endosomes exclusively rather than through increased endocytosis. These results reveal substantial dynamism in the surface ErbB2 pool and clearly demonstrate the significance of endosomal sorting in the maintenance of ErbB2 surface distribution, a critical feature of its biological function.
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