Metastasis: crosstalk between tissue mechanics and tumour cell plasticity

Br J Cancer. 2021 Jan;124(1):49-57. doi: 10.1038/s41416-020-01150-7. Epub 2020 Nov 18.


Despite the fact that different genetic programmes drive metastasis of solid tumours, the ultimate outcome is the same: tumour cells are empowered to pass a series of physical hurdles to escape the primary tumour and disseminate to other organs. Epithelial-to-mesenchymal transition (EMT) has been proposed to drive the detachment of individual cells from primary tumour masses and facilitate the subsequent establishment of metastases in distant organs. However, this concept has been challenged by observations from pathologists and from studies in animal models, in which partial and transient acquisition of mesenchymal traits is seen but tumour cells travel collectively rather than as individuals. In this review, we discuss how crosstalk between a hybrid E/M state and variations in the mechanical aspects of the tumour microenvironment can provide tumour cells with the plasticity required for strategies to navigate surrounding tissues en route to dissemination. Targeting such plasticity provides therapeutic opportunities to combat metastasis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Plasticity / physiology*
  • Epithelial-Mesenchymal Transition / physiology*
  • Humans
  • Neoplasm Invasiveness / pathology*
  • Neoplasms / metabolism
  • Neoplasms / pathology*
  • Receptor Cross-Talk / physiology
  • Tumor Microenvironment / physiology*