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

Nat Commun. 2017 May 16:8:15237. doi: 10.1038/ncomms15237.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism*
  • Animals
  • Breast / pathology
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology*
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism
  • Cell Line
  • Cell Movement
  • Cell Proliferation*
  • Cell Transformation, Neoplastic / pathology*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Datasets as Topic
  • Drosophila
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Phosphorylation
  • RNA, Small Interfering / metabolism
  • Stress Fibers / pathology*
  • Time-Lapse Imaging
  • Tissue Array Analysis
  • Up-Regulation
  • src-Family Kinases / metabolism

Substances

  • Actins
  • Cell Adhesion Molecules
  • DNA-Binding Proteins
  • ENA-VASP proteins
  • EVL protein, human
  • RNA, Small Interfering
  • src-Family Kinases