Radiation-induced myosin IIA expression stimulates collagen type I matrix reorganization

Radiother Oncol. 2013 Jul;108(1):162-7. doi: 10.1016/j.radonc.2013.04.001. Epub 2013 Jun 3.


Background and purpose: Extracellular matrix (ECM) reorganization critically contributes to breast cancer (BC) progression and radiotherapy response. We investigated the molecular background and functional consequences of collagen type I (col-I) reorganization by irradiated breast cancer cells (BCC).

Materials and methods: Radiation-induced (RI) col-I reorganization was evaluated for MCF-7/6, MCF-7/AZ, T47D and SK-BR-3 BCC. Phase-contrast microscopy and a stressed matrix contraction assay were used for visualization and quantification of col-I reorganization. Cell-matrix interactions were assessed by the inhibition of β1 integrin (neutralizing antibody 'P5D2') or focal adhesion kinase (FAK; GSK22560098 small molecule kinase inhibitor). The role of the actomyosin cytoskeleton was explored by western blotting analysis of myosin II expression and activity; and by gene silencing of myosin IIA and pharmacological inhibition of the actomyosin system (blebbistatin, cytochalasin D). BCC death was evaluated by propidium iodide staining.

Results: We observed a radiation dose-dependent increase of col-I reorganization by BCC. β1 Integrin/FAK-mediated cell-matrix interactions are essential for RI col-I reorganization. Irradiated BCC are characterized by increased myosin IIA expression and myosin IIA-dependent col-I reorganization. Moreover, RI col-I reorganization by BCC is associated with decreased BCC death, as suggested by pharmacological targeting of the β1 integrin/FAK/myosin IIA pathway.

Conclusions: Our data indicate the role of myosin IIA in col-I reorganization by irradiated BCC and reciprocal BCC death.

Keywords: Actomyosin; Breast cancer; Cell–matrix interactions; Collagen; ECM remodeling; Ionizing radiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actomyosin / physiology
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Breast Neoplasms / radiotherapy*
  • Collagen Type I / chemistry*
  • Female
  • Focal Adhesion Protein-Tyrosine Kinases / physiology
  • Humans
  • Integrin beta1 / physiology
  • MCF-7 Cells
  • Nonmuscle Myosin Type IIA / physiology*


  • Collagen Type I
  • Integrin beta1
  • Actomyosin
  • Focal Adhesion Protein-Tyrosine Kinases
  • Nonmuscle Myosin Type IIA