Oncogenic signaling alters cell shape and mechanics to facilitate cell division under confinement

When cells enter mitosis, they become spherical and mechanically stiffen. We used MCF10A cell lines as a model system in which to investigate the effect of induced oncogene expression on mitotic entry. We find that activation of oncogenic Ras ^V12 , for as little as five hours, changes the way cells divide. Ras ^V12 -dependent activation of the MEK-ERK signalling cascade alters acto-myosin contractility to enhance mitotic rounding. Ras ^V12 also affects cell mechanics, so that Ras ^V12 expressing cells are softer in interphase but stiffen more upon entry into mitosis. As a consequence, Ras ^V12 expression augments the ability of cells to round up and divide faithfully when confined underneath a stiff hydrogel. Conversely, inhibition of the Ras-ERK pathway reduces mitotic rounding under confinement, resulting in chromosome segregation defects. These data suggest a novel mechanism by which oncogenic Ras-ERK signalling can aid division in stiff environments like those found in tumours.