Actin stress fiber organization promotes cell stiffening and proliferation of pre-invasive breast cancer cells

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Sandra Tavares - , Instituto Gulbenkian de Ciência (Author)
  • André Filipe Vieira - , University of Porto (Author)
  • Anna Verena Taubenberger - , Oncomechanics (Research Group), Chair of Cellular Machines (Author)
  • Margarida Araújo - , Instituto Gulbenkian de Ciência (Author)
  • Nuno Pimpao Martins - , Instituto Gulbenkian de Ciência (Author)
  • Catarina Brás-Pereira - , Instituto Gulbenkian de Ciência (Author)
  • António Polónia - , University of Porto (Author)
  • Maik Herbig - , TUD Dresden University of Technology (Author)
  • Clara Barreto - , Instituto Gulbenkian de Ciência (Author)
  • Oliver Otto - , TUD Dresden University of Technology (Author)
  • Joana Cardoso - , Instituto Gulbenkian de Ciência, Ophiomics-Precision Medicine (Author)
  • José B. Pereira-Leal - , Instituto Gulbenkian de Ciência, Ophiomics-Precision Medicine (Author)
  • Jochen Guck - , Chair of Cellular Machines (Author)
  • Joana Paredes - , University of Porto (Author)
  • Florence Janody - , University of Porto (Author)

Abstract

Studies of the role of actin in tumour progression have highlighted its key contribution in cell softening associated with cell invasion. Here, using a human breast cell line with conditional Src induction, we demonstrate that cells undergo a stiffening state prior to acquiring malignant features. This state is characterized by the transient accumulation of stress fibres and upregulation of Ena/VASP-like (EVL). EVL, in turn, organizes stress fibres leading to transient cell stiffening, ERK-dependent cell proliferation, as well as enhancement of Src activation and progression towards a fully transformed state. Accordingly, EVL accumulates predominantly in premalignant breast lesions and is required for Src-induced epithelial overgrowth in Drosophila. While cell softening allows for cancer cell invasion, our work reveals that stress fibre-mediated cell stiffening could drive tumour growth during premalignant stages. A careful consideration of the mechanical properties of tumour cells could therefore offer new avenues of exploration when designing cancer-targeting therapies.

Details

Original languageEnglish
Article number15237
JournalNature communications
Volume8
Publication statusPublished - 16 May 2017
Peer-reviewedYes

External IDs

PubMed 28508872