ArticleMolecular biology of the cell2017
Liquid-phase electron microscopy of molecular drug response in breast cancer cells reveals irresponsive cell subpopulations related to lack of HER2 homodimers.
Article in Molecular biology of the cell, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
What it found
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Who cites it
10 citing papers in PubMed, 22 citations in OpenAlex.
- Contrast by electron microscopy in thick biological specimens.Journal of microscopy · 2025Article
- Imaging of Hydrated and Living Cells in Transmission Electron Microscope: Summary, Challenges, and Perspectives.ACS nano · 2025Review
- EGFR-directed antibodies promote HER2 ADC internalization and efficacy.Cell reports. Medicine · 2024Article
- Article
- Supra-Molecular Assemblies of ORAI1 at Rest Precede Local Accumulation into Puncta after Activation.International journal of molecular sciences · 2021Article
- EGFR Expression in HER2-Driven Breast Cancer Cells.International journal of molecular sciences · 2020Article
- Liquid cell transmission electron microscopy and its applications.Royal Society open science · 2020Review
- Mathematical modeling of drug-induced receptor internalization in the HER2-positive SKBR3 breast cancer cell-line.Scientific reports · 2019Article
- Visualisation of HER2 homodimers in single cells from HER2 overexpressing primary formalin fixed paraffin embedded tumour tissue.Molecular medicine (Cambridge, Mass.) · 2019Article
- Linear Chains of HER2 Receptors Found in the Plasma Membrane Using Liquid-Phase Electron Microscopy.Biophysical journal · 2018Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The development of drug resistance in cancer poses a major clinical problem. An example is human epidermal growth factor receptor 2 (HER2) overexpressing breast cancer often treated with anti-HER2 antibody therapies, such as trastuzumab. Since drug resistance is rooted mainly in tumor cell heterogeneity, we examined the drug effect in different subpopulations of SKBR3 breast cancer cells, and compared the results with a drug resistant cell line, HCC1954. Correlative light microscopy and liquid-phase scanning transmission electron microscopy (STEM) were used to quantitatively analyze HER2 responses upon drug binding, whereby many tens of whole cells were imaged. Trastuzumab was found to selectively cross-link and down regulate HER2 homodimers from the plasma membranes of bulk cancer cells. In contrast, HER2 resided mainly as monomers in rare subpopulations of resting- and cancer stem cells (CSCs), and these monomers were not internalized after drug binding. The HER2 distribution was hardly influenced by trastuzumab for the HCC1954 cells. These findings show that resting cells and CSCs are irresponsive to the drug, and thus point towards a molecular explanation behind the origin of drug resistance. This analytical method is broadly applicable to study membrane protein interactions in the intact plasma membrane, while accounting for cell heterogeneity.
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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.