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

Autor:	Matthews HK; 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: h.matthews@ucl.ac.uk., Ganguli S; MRC Laboratory for Molecular Cell Biology, University College London, Gower Street, London WC1E 6BT, UK., Plak K; 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., Taubenberger AV; Biotechnology Center, Technische Universität Dresden, Tatzberg 47/49, 01307 Dresden, Germany., Win Z; 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., Williamson M; MRC Laboratory for Molecular Cell Biology, University College London, Gower Street, London WC1E 6BT, UK., Piel M; Institut Curie and Institut Pierre Gilles de Gennes, PSL Research University, CNRS, UMR 144, Paris, France., Guck J; 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., Baum B; 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: b.baum@ucl.ac.uk.
Jazyk:	angličtina
Zdroj:	Developmental cell [Dev Cell] 2020 Mar 09; Vol. 52 (5), pp. 563-573.e3. Date of Electronic Publication: 2020 Feb 06.
DOI:	10.1016/j.devcel.2020.01.004
Abstrakt:	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. Competing Interests: Declaration of Interests The authors declare no competing interests. (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu