High cell-surface density of HER2 deforms cell membranes

Inhee Chung (), Mike Reichelt, Lily Shao, Robert W. Akita, Hartmut Koeppen, Linda Rangell, Gabriele Schaefer, Ira Mellman and Mark X. Sliwkowski ()
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Inhee Chung: Molecular Oncology, Genentech, 1 DNA Way
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

Nature Communications, 2016, vol. 7, issue 1, 1-11

Abstract: 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.

Date: 2016
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DOI: 10.1038/ncomms12742

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