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Oncogenic Ras deregulates cell-substrate interactions during mitotic rounding and respreading to alter cell division orientation

Ganguli, Sushila; Wyatt, Tom; Nyga, Agata; Lawson, Rachel H; Meyer, Tim; Baum, Buzz; Matthews, Helen K; (2023) Oncogenic Ras deregulates cell-substrate interactions during mitotic rounding and respreading to alter cell division orientation. Current Biology 10.1016/j.cub.2023.05.061. (In press). Green open access

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Abstract

Oncogenic Ras has been shown to change the way cancer cells divide by increasing the forces generated during mitotic rounding. In this way, RasV12 enables cancer cells to divide across a wider range of mechanical environments than normal cells. Here, we identify a further role for oncogenic Ras-ERK signaling in division by showing that RasV12 expression alters the shape, division orientation, and respreading dynamics of cells as they exit mitosis. Many of these effects appear to result from the impact of RasV12 signaling on actomyosin contractility, because RasV12 induces the severing of retraction fibers that normally guide spindle positioning and provide a memory of the interphase cell shape. In support of this idea, the RasV12 phenotype is reversed by inhibition of actomyosin contractility and can be mimicked by the loss of cell-substrate adhesion during mitosis. Finally, we show that RasV12 activation also perturbs division orientation in cells cultured in 2D epithelial monolayers and 3D spheroids. Thus, the induction of oncogenic Ras-ERK signaling leads to rapid changes in division orientation that, along with the effects of RasV12 on cell growth and cell-cycle progression, are likely to disrupt epithelial tissue organization and contribute to cancer dissemination.

Type: Article
Title: Oncogenic Ras deregulates cell-substrate interactions during mitotic rounding and respreading to alter cell division orientation
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.cub.2023.05.061
Publisher version: https://doi.org/10.1016/j.cub.2023.05.061
Language: English
Additional information: © 2023 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Keywords: MAPK signaling, actin cytoskeleton, cell division, division orientation, focal adhesions, mitosis, mitotic rounding, mitotic spindle
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology
URI: https://discovery.ucl.ac.uk/id/eprint/10172561
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