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

Area of Science:

• Cell Biology
• Cancer Research
• Mechanobiology

Background:

• Oncogenic Ras signaling influences cancer cell division mechanics.
• Ras^V12 expression increases forces during mitotic rounding, allowing division in diverse mechanical environments.

Purpose of the Study:

• To investigate the role of oncogenic Ras-ERK signaling in cell division beyond mitotic rounding.
• To determine how Ras^V12 affects cell shape, division orientation, and post-mitotic behavior.

Main Methods:

• Studied the impact of Ras^V12 expression on cell division.
• Investigated the role of actomyosin contractility and cell-substrate adhesion.
• Observed cells in 2D epithelial monolayers and 3D spheroids.

Main Results:

• Ras^V12 expression alters cell shape, division orientation, and respreading dynamics post-mitosis.
• Ras^V12 severs retraction fibers, impacting spindle positioning and cell shape memory.
• Inhibition of actomyosin contractility or loss of cell-substrate adhesion reverses Ras^V12 effects.
• Ras^V12 perturbs division orientation in both 2D and 3D culture models.

Conclusions:

• Oncogenic Ras-ERK signaling rapidly changes cell division orientation.
• Ras^V12-induced changes disrupt epithelial tissue organization.
• These alterations likely contribute to cancer dissemination by affecting tissue structure and cell behavior.