ERBB2 overexpression triggers transient high mechanoactivity of breast tumor cells

Abstract

Biomechanical properties of tumor cells play an important role for the metastatic capacity of cancer. Cellular changes of viscoelastic features are prerequisite for cancer progression since they are essential for proliferation and metastasis. However, only little is known about the way how expression of oncogenes influences these biomechanical properties. To address this aspect we used a breast cancer cell line with inducible expression of an oncogenic version of ERBB2. ERBB2 is known to be correlated with bad prognosis in breast cancer. Cell elasticity was determined by the Optical Stretcher, where suspended cells are deformed by two slightly divergent laser beams. We found that induction of ERBB2 caused remarkable biomechanical alterations of the MCF-7 cells after 24 h: the cells actively contracted in response to mechanical stimuli, a phenomenon known as mechanoactivation. After this period, as the cells became senescent, the mechanoactivity returned to control levels. Time-resolved gene array analysis revealed that mechanoactivation was accompanied by temporal upregulation of 46 cytoskeletal genes. A possible role of these genes in tumor progression was investigated by expression analyses of 766 breast cancer patients. This showed an association of 12 out of these 46 genes with increased risk of metastasis. Our results demonstrate that overexpression of ERBB2 causes mechanoactivation of tumor cells, which may enhance tumor cell motility fostering distant metastasis.

Evaluation of single‐cell biomechanics as potential marker for oral squamous cell carcinomas: a pilot study

“…In principle, malignant transformation causes cell softening. This has been shown for cell lines and for tumor tissues of different origins (Remmerbach et al , ; Fritsch et al , ; Martin et al , ).…”

The tumor suppressor CDX2 opposes pro-metastatic biomechanical modifications of colon cancer cells through organization of the actin cytoskeleton

“…In summary, this study describes for the first time a CDX2/VAV3/RHO signaling cascade that impacts on the biomechanical features of colon cancer cells, namely elasticity. Although the importance of these features for the metastatic process is more and more appreciated, the molecular mechanisms involved remain elusive and have only been examined in a limited number of studies [49,50]. Beyond CDX2, our data also illustrate how various features of the epithelial tissue may oppose colon cancer cell dissemination.…”

Annexin A7 is required for ESCRT III-mediated plasma membrane repair

“…To identify injury-induced changes in the plasma membrane proteome we used MCF7 breast cancer cells expressing a N-terminally truncated 95 kDa version of ErbB2 (p95ErbB2), which increases their membrane dynamics and invasiveness 28,29 . MCF7-p95ErbB2 cells were metabolically labeled by stable isotope-labeling by amino acids in cell culture (SILAC) and the plasma membrane proteins were tagged by biotin.…”