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 RasV12, for as little as five hours, changes the way cells divide. RasV12-dependent activation of the MEK-ERK signalling cascade alters acto-myosin contractility to enhance mitotic rounding. RasV12 also affects cell mechanics, so that RasV12 expressing cells are softer in interphase but stiffen more upon entry into mitosis. As a consequence, RasV12 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.