Communications Biology (Feb 2022)

Ret kinase-mediated mechanical induction of colon stem cells by tumor growth pressure stimulates cancer progression in vivo

  • Thanh Huong Nguyen Ho-Bouldoires,
  • Kévin Sollier,
  • Laura Zamfirov,
  • Florence Broders-Bondon,
  • Démosthène Mitrossilis,
  • Sebastian Bermeo,
  • Coralie L. Guerin,
  • Anna Chipont,
  • Gabriel Champenois,
  • Renaud Leclère,
  • Nicolas André,
  • Laurent Ranno,
  • Aude Michel,
  • Christine Ménager,
  • Didier Meseure,
  • Charlie Demené,
  • Mickael Tanter,
  • Maria Elena Fernández-Sánchez,
  • Emmanuel Farge

DOI
https://doi.org/10.1038/s42003-022-03079-4
Journal volume & issue
Vol. 5, no. 1
pp. 1 – 18

Abstract

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Ho-Bouldoires, Sollier, Zamfirov and Broders-Bondon et al. show that high frequency pulsatile mechanical stresses maintain the physiological level of mice colon stem cells through the mechanosensitive Ret kinase and that Ret activation is elevated in human colon cancer tissue. They go on to show that the maintenance of such stimulation in the form of tumour growth pressure results in mechanically-induced hyperproliferation and tumorigenic transformation of stem cells, which can be prevented by Ret kinase inhibition.