The role of RAS oncogenes in controlling epithelial mechanics. Issue 1 (January 2023)

• Record Type: Journal Article
• Authors: Nyga, Agata; Ganguli, Sushila; Matthews, Helen K.; Baum, Buzz
• Is Part Of: Trends in cell biology. Volume 33:Issue 1(2023)
• Page Start: 60
• Page End: 69
• Publication Date: 2023-01
• Subjects: RAS -- oncogene -- epithelia -- mechanobiology -- actin -- myosin -- mechanotransduction -- YAP/TAZ signalling -- tissue mechanics; Cytology -- Periodicals; Cytology -- Research -- Periodicals; 571.6
• DOI: 10.1016/j.tcb.2022.09.002
• Languages: English
• ISSNs: 0962-8924

Abstract

Abstract : Mutations in RAS are key oncogenic drivers and therapeutic targets. Oncogenic Ras proteins activate a network of downstream signalling pathways, including extracellular signal-regulated kinase (ERK) and phosphatidylinositol 3-kinase (PI3K), promoting cell proliferation and survival. However, there is increasing evidence that RAS oncogenes also alter the mechanical properties of both individual malignant cells and transformed tissues. Here we discuss the role of oncogenic RAS in controlling mechanical cell phenotypes and how these mechanical changes promote oncogenic transformation in single cells and tissues. RAS activation alters actin organisation and actomyosin contractility. These changes alter cell rheology and impact mechanosensing through changes in substrate adhesion and YAP/TAZ-dependent mechanotransduction. We then discuss how these changes play out in cell collectives and epithelial tissues by driving large-scale tissue deformations and the expansion of malignant cells. Uncovering how RAS oncogenes alter cell mechanics will lead to a better understanding of the morphogenetic processes that underlie tumour formation in RAS-mutant cancers. Highlights: Activation of RAS oncogenes and the downstream extracellular signal-regulated kinase/mitogen-activated protein kinase pathway alters actomyosin contractility, leading to changes in the mechanical properties of single cells and tissues. Oncogenic RAS alters the ability of cells to sense the stiffness of their environment through changes to cell contractility and substrate adhesion. Oncogenic RAS alters mechanotransduction via the YAP/TAZ signalling pathway. Mechanical changes in RAS-activated cells can drive large-scale deformations in epithelial tissues, including buckling and folding. The balance between elimination and preservation of RAS-transformed cells within a healthy epithelium is influenced by their differential mechanical phenotypes.