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High cell-surface density of HER2 deforms cell membranes

Author

Listed:
  • Inhee Chung

    (Molecular Oncology, Genentech, 1 DNA Way
    Present address: Janelia Research Campus, Howard Hughes Medical Institute, 19700 Helix Drive, Ashburn, Virginia 20147, USA)

  • Mike Reichelt

    (Research Pathology, Genentech, 1 DNA Way)

  • Lily Shao

    (Translational Oncology, Genentech, 1 DNA Way)

  • Robert W. Akita

    (Molecular Oncology, Genentech, 1 DNA Way)

  • Hartmut Koeppen

    (Research Pathology, Genentech, 1 DNA Way)

  • Linda Rangell

    (Research Pathology, Genentech, 1 DNA Way)

  • Gabriele Schaefer

    (Translational Oncology, Genentech, 1 DNA Way)

  • Ira Mellman

    (Cancer Immunology, Genentech, 1 DNA Way)

  • Mark X. Sliwkowski

    (Molecular Oncology, Genentech, 1 DNA Way)

Abstract

Breast cancers (BC) with HER2 overexpression (referred to as HER2 positive) progress more aggressively than those with normal expression. Targeted therapies against HER2 can successfully delay the progression of HER2-positive BC, but details of how this overexpression drives the disease are not fully understood. Using single-molecule biophysical approaches, we discovered a new effect of HER2 overexpression on disease-relevant cell biological changes in these BC. We found HER2 overexpression causes deformation of the cell membranes, and this in turn disrupts epithelial features by perturbing cell–substrate and cell–cell contacts. This membrane deformation does not require receptor signalling activities, but results from the high levels of HER2 on the cell surface. Our finding suggests that early-stage morphological alterations of HER2-positive BC cells during cancer progression can occur in a physical and signalling-independent manner.

Suggested Citation

  • Inhee Chung & Mike Reichelt & Lily Shao & Robert W. Akita & Hartmut Koeppen & Linda Rangell & Gabriele Schaefer & Ira Mellman & Mark X. Sliwkowski, 2016. "High cell-surface density of HER2 deforms cell membranes," Nature Communications, Nature, vol. 7(1), pages 1-11, November.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms12742
    DOI: 10.1038/ncomms12742
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    Cited by:

    1. Daniel P. Arnold & Yaxin Xu & Sho C. Takatori, 2023. "Antibody binding reports spatial heterogeneities in cell membrane organization," Nature Communications, Nature, vol. 14(1), pages 1-13, December.

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