ArticleMolecular biology of the cell2013
The HSP90 inhibitor geldanamycin perturbs endosomal structure and drives recycling ErbB2 and transferrin to modified MVBs/lysosomal compartments.
Article in Molecular biology of the cell, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 47 citations in OpenAlex.
- Intracellular Nanopharmacology of Trastuzumab Deruxtecan Reveals Lysosome-Centered Organelle Vulnerabilities in HER2-Positive Breast Cancer Cells.ACS nano medicine · 2026Article
- Heat shock proteins at the crossroads of endosomal trafficking pathways.Cell biology and toxicology · 2025Review
- Enhanced HER2 internalization by clathrin-dependent endocytosis in non-small cell lung cancer positive for HER2 mutations.British journal of cancer · 2025Article
- Irreversible tyrosine kinase inhibitors induce the endocytosis and downregulation of ErbB2.Biochemistry and biophysics reports · 2023Article
- Cell surface protein aggregation triggers endocytosis to maintain plasma membrane proteostasis.Nature communications · 2023Article
- EGFR trafficking: effect of dimerization, dynamics, and mutation.Frontiers in oncology · 2023Review
- Article
- Regulation of Protein Transport Pathways by the Cytosolic Hsp90s.Biomolecules · 2022Review
- Imaging Endocytosis Dynamics in Health and Disease.Membranes · 2022Review
- RAB5A expression is a predictive biomarker for trastuzumab emtansine in breast cancer.Nature communications · 2021Article
- Impact of Endocytosis Mechanisms for the Receptors Targeted by the Currently Approved Antibody-Drug Conjugates (ADCs)-A Necessity for Future ADC Research and Development.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Imaging of Endocytic Trafficking and Extracellular Vesicles Released Under Neratinib Treatment in ERBB2The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2021Article
- Comparative Evaluation of Engineered Polypeptide Scaffolds in HER2-Targeting Magnetic Nanocarrier Delivery.ACS omega · 2021Article
- The deubiquitylase USP2 maintains ErbB2 abundance via counteracting endocytic degradation and represents a therapeutic target in ErbB2-positive breast cancer.Cell death and differentiation · 2020Article
- Improving Receptor-Mediated Intracellular Access and Accumulation of Antibody Therapeutics-The Tale of HER2.Antibodies (Basel, Switzerland) · 2020Review
- Molecular Stressors Engender Protein Connectivity Dysfunction through Aberrant N-Glycosylation of a Chaperone.Cell reports · 2020Article
- Strategic Trastuzumab Mediated Crosslinking Driving Concomitant HER2 and HER3 Endocytosis and Degradation in Breast Cancer.Journal of Cancer · 2020Article
- Mathematical modeling of drug-induced receptor internalization in the HER2-positive SKBR3 breast cancer cell-line.Scientific reports · 2019Article
- SORLA regulates endosomal trafficking and oncogenic fitness of HER2.Nature communications · 2019Article
- Article
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Authors and funding
10 authors at 6 institutions in 4 countries.
Funding
Abstract
The ErbB2 receptor is a clinically validated cancer target whose internalization and trafficking mechanisms remain poorly understood. HSP90 inhibitors, such as geldanamycin (GA), have been developed to target the receptor to degradation or to modulate downstream signaling. Despite intense investigations, the entry route and postendocytic sorting of ErbB2 upon GA stimulation have remained controversial. We report that ErbB2 levels inversely impact cell clathrin-mediated endocytosis (CME) capacity. Indeed, the high levels of the receptor are responsible for its own low internalization rate. GA treatment does not directly modulate ErbB2 CME rate but it affects ErbB2 recycling fate, routing the receptor to modified multivesicular endosomes (MVBs) and lysosomal compartments, by perturbing early/recycling endosome structure and sorting capacity. This activity occurs irrespective of the cargo interaction with HSP90, as both ErbB2 and the constitutively recycled, HSP90-independent, transferrin receptor are found within modified endosomes, and within aberrant, elongated recycling tubules, leading to modified MVBs/lysosomes. We propose that GA, as part of its anticancer activity, perturbs early/recycling endosome sorting, routing recycling cargoes toward mixed endosomal compartments.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.