High cell-surface density of HER2 deforms cell membranes.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 27599456.
- Also identified by DOI 10.1038/ncomms12742 and PMC identifier 5023959.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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.
Medical subject headings
- Breast Neoplasms
- Cell Membrane
- Gene Expression Regulation, Neoplastic
- Erb-b2 Receptor Tyrosine Kinases