Targeting Mechanotransduction in Osteosarcoma: A Comparative Oncology Perspective

Int J Mol Sci. 2020 Oct 14;21(20):7595. doi: 10.3390/ijms21207595.

Abstract

Mechanotransduction is the process in which cells can convert extracellular mechanical stimuli into biochemical changes within a cell. While this a normal process for physiological development and function in many organ systems, tumour cells can exploit this process to promote tumour progression. Here we summarise the current state of knowledge of mechanotransduction in osteosarcoma (OSA), the most common primary bone tumour, referencing both human and canine models and other similar mesenchymal malignancies (e.g., Ewing sarcoma). Specifically, we discuss the mechanical properties of OSA cells, the pathways that these cells utilise to respond to external mechanical cues, and mechanotransduction-targeting strategies tested in OSA so far. We point out gaps in the literature and propose avenues to address them. Understanding how the physical microenvironment influences cell signalling and behaviour will lead to the improved design of strategies to target the mechanical vulnerabilities of OSA cells.

Keywords: Hippo signalling; TAZ; YAP; comparative oncology; ezrin; mechanotransduction; molecular targeted therapy; myocardin-related transcription factor-A/-B; osteosarcoma.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Bone Neoplasms / drug therapy
  • Bone Neoplasms / genetics
  • Bone Neoplasms / metabolism*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mechanotransduction, Cellular / drug effects*
  • Osteoclasts / drug effects
  • Osteoclasts / metabolism
  • Osteosarcoma / drug therapy
  • Osteosarcoma / genetics
  • Osteosarcoma / metabolism*

Substances

  • Antineoplastic Agents