Local light-activation of the Src oncoprotein in an epithelial monolayer promotes collective extrusion
| Autor: | Christiane Oddou, Pascal Silberzan, Olivier Destaing, Isabelle Bonnet, Sarah Moitrier, Adèle Kerjouan, Nastassia Pricoupenko, Aude Battistella |
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| Přispěvatelé: | Laboratoire Physico-Chimie Curie [Institut Curie] (PCC), Institut Curie [Paris]-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]) |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0303 health sciences
Chemistry [PHYS.PHYS.PHYS-BIO-PH]Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph] Epithelial monolayer General Physics and Astronomy lcsh:Astrophysics Optogenetics medicine.disease_cause Epithelium In vitro lcsh:QC1-999 Cell biology 03 medical and health sciences 0302 clinical medicine medicine.anatomical_structure Monolayer lcsh:QB460-466 medicine Light activation Carcinogenesis 030217 neurology & neurosurgery lcsh:Physics 030304 developmental biology Proto-oncogene tyrosine-protein kinase Src |
| Zdroj: | Communications Physics Communications Physics, 2019, 2 (1), ⟨10.1038/s42005-019-0198-5⟩ Communications Physics, Vol 2, Iss 1, Pp 1-11 (2019) |
| DOI: | 10.1038/s42005-019-0198-5⟩ |
| Popis: | Transformed isolated cells are usually extruded from normal epithelia and subsequently eliminated. However, multicellular tumors outcompete healthy cells, highlighting the importance of collective effects. Here, we investigate this situation in vitro by controlling in space and time the activity of the Src oncoprotein within a normal Madin–Darby Canine Kidney (MDCK) epithelial cell monolayer. Using an optogenetics approach with cells expressing a synthetic light-sensitive version of Src (optoSrc), we reversibly trigger the oncogenic activity by exposing monolayers to well-defined light patterns. We show that small populations of activated optoSrc cells embedded in the non-transformed monolayer collectively extrude as a tridimensional aggregate and remain alive, while the surrounding normal cells migrate towards the exposed area. This phenomenon requires an interface between normal and transformed cells and is partially reversible. Traction forces show that Src-activated cells either actively extrude or are pushed out by the surrounding cells in a non-autonomous way. To study the onset of carcinogenesis, the authors use an optogenetics approach to selectively activate with light the Src oncoprotein in cells of an epithelium with a good control in time and space. The transformed cells collectively extrude as a tridimensional aggregate from the cell sheet while remaining alive and in parallel cells of the monolayer converge toward the locus of extrusion. |
| Databáze: | OpenAIRE |
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