The role of RAS oncogenes in controlling epithelial mechanics

Agata Nyga1, Sushila Ganguli2, Helen K Matthews3

  • 1Medical Research Council Laboratory of Molecular Biology, Cambridge, CB2 0QH, UK.

Trends in Cell Biology
|September 29, 2022
PubMed

Insights

RAS oncogenes alter cell mechanics, affecting actin organization and contractility. These mechanical changes drive cell proliferation and tissue deformation in cancer development.

Area of Science:

  • Oncology
  • Cell Biology
  • Biophysics

Background:

  • RAS mutations are central drivers of cancer and targets for therapy.
  • Oncogenic Ras proteins activate signaling pathways like ERK and PI3K, promoting cell growth and survival.
  • Emerging evidence links RAS oncogenes to altered mechanical properties of cancer cells and tissues.

Purpose of the Study:

  • To explore the role of oncogenic RAS in regulating cellular mechanical phenotypes.
  • To understand how RAS-induced mechanical changes contribute to oncogenic transformation in single cells and tissues.

Main Methods:

  • Analysis of RAS activation effects on actin organization and actomyosin contractility.
  • Investigation of changes in cell rheology, substrate adhesion, and mechanosensing pathways (YAP/TAZ).
  • Examination of how these mechanical alterations influence collective cell behavior and tissue-level deformations.

Main Results:

  • RAS activation modifies actin cytoskeleton organization and actomyosin contractility.
  • Altered cell mechanics impact cell rheology and mechanosensing.
  • These changes facilitate tissue deformation and malignant cell expansion in collective settings.

Conclusions:

  • Understanding RAS-mediated mechanical alterations is crucial for comprehending tumor formation in RAS-mutant cancers.
  • Investigating cell mechanics provides insights into the morphogenetic processes underlying cancer progression.
  • Targeting mechanical pathways may offer novel therapeutic strategies for RAS-driven cancers.

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