Oncogenic Signaling Alters Cell Shape and Mechanics to Facilitate Cell Division under Confinement

Helen K Matthews; Sushila Ganguli; Katarzyna Plak; Anna V Taubenberger; Zaw Win; Max Williamson; Matthieu Piel; Jochen Guck; Buzz Baum

doi:10.1016/j.devcel.2020.01.004

Oncogenic Signaling Alters Cell Shape and Mechanics to Facilitate Cell Division under Confinement

Dev Cell. 2020 Mar 9;52(5):563-573.e3. doi: 10.1016/j.devcel.2020.01.004. Epub 2020 Feb 6.

Authors

Helen K Matthews¹, Sushila Ganguli², Katarzyna Plak³, Anna V Taubenberger⁴, Zaw Win⁵, Max Williamson², Matthieu Piel⁶, Jochen Guck⁷, Buzz Baum⁸

Affiliations

¹ MRC Laboratory for Molecular Cell Biology, University College London, Gower Street, London WC1E 6BT, UK; The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK. Electronic address: [email protected].
² MRC Laboratory for Molecular Cell Biology, University College London, Gower Street, London WC1E 6BT, UK.
³ MRC Laboratory for Molecular Cell Biology, University College London, Gower Street, London WC1E 6BT, UK; Biotechnology Center, Technische Universität Dresden, Tatzberg 47/49, 01307 Dresden, Germany.
⁴ Biotechnology Center, Technische Universität Dresden, Tatzberg 47/49, 01307 Dresden, Germany.
⁵ MRC Laboratory for Molecular Cell Biology, University College London, Gower Street, London WC1E 6BT, UK; The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
⁶ Institut Curie and Institut Pierre Gilles de Gennes, PSL Research University, CNRS, UMR 144, Paris, France.
⁷ Biotechnology Center, Technische Universität Dresden, Tatzberg 47/49, 01307 Dresden, Germany; Max Planck Institute for the Science of Light & Max-Planck-Zentrum für Physik und Medizin, Staudtstraße 2, 91058 Erlangen, Germany.
⁸ MRC Laboratory for Molecular Cell Biology, University College London, Gower Street, London WC1E 6BT, UK; The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK; Institute for the Physics of Living Systems, University College London, London WC1E 6BT, UK. Electronic address: [email protected].

Abstract

To divide in a tissue, both normal and cancer cells become spherical and mechanically stiffen as they enter mitosis. We investigated the effect of oncogene activation on this process in normal epithelial cells. We found that short-term induction of oncogenic Ras^V12 activates downstream mitogen-activated protein kinase (MEK-ERK) signaling to alter cell mechanics and enhance mitotic rounding, so that Ras^V12-expressing cells are softer in interphase but stiffen more upon entry into mitosis. These Ras^V12-dependent changes allow cells to round up and divide faithfully when confined underneath a stiff hydrogel, conditions in which normal cells and cells with reduced levels of Ras-ERK signaling suffer multiple spindle assembly and chromosome segregation errors. Thus, by promoting cell rounding and stiffening in mitosis, oncogenic Ras^V12 enables cells to proliferate under conditions of mechanical confinement like those experienced by cells in crowded tumors.

Keywords: ERK; MAPK signaling; MEK; Ras; actin; cancer; cell confinement; cell mechanics; mitosis; mitotic rounding.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Line
Cell Shape*
Chromosome Segregation
Humans
MAP Kinase Signaling System*
Mitosis*
Spindle Apparatus / metabolism
Stress, Mechanical*
ras Proteins / metabolism*

Substances

ras Proteins

Abstract

Publication types

MeSH terms

Substances

Grants and funding