title: 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.
authors.affiliation: Department of Diagnostic and Interventional Radiology, University Hospital Leipzig, and University Leipzig, Leipzig, Germany. mmartin@rz.uni-leipzig.de
authors.forename: Mireille
authors.initials: M
authors.lastname: Martin
authors.forename: Karla
authors.initials: K
authors.lastname: Müller
authors.forename: Cristina
authors.initials: C
authors.lastname: Cadenas
authors.forename: Matthias
authors.initials: M
authors.lastname: Hermes
authors.forename: Mareike
authors.initials: M
authors.lastname: Zink
authors.forename: Jan G
authors.initials: JG
authors.lastname: Hengstler
authors.forename: Josef A
authors.initials: JA
authors.lastname: Käs
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D015153:Blotting, Western; D001940:Breast / Q000378:metabolism* / Q000473:pathology; D001943:Breast Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D015331:Cohort Studies; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D040542:Mechanotransduction, Cellular; D009362:Neoplasm Metastasis; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases