E-cadherin, actin, microtubules and FAK dominate different spheroid formation phases and important elements of tissue integrity

  • Spheroids resemble features of tissues and serve as model systems to study cell–cell and cell–ECM interactions in non-adhesive three-dimensional environments. Although it is generally accepted that mature spheroids resemble tissue properties very well, no studies relate different phases in the spheroid formation processes that contribute to tissue integrity. Tissue integrity involves the cellular processes adhesion formation, adhesion reinforcement, rearrangement as well as proliferation. They maintain the structure and function of tissues and, upon dysregulation, contribute to malignancy. We investigated spheroid formation dynamics in cell lines of different metastatic potential. We dissected spheroid formation into phases of aggregation, compaction and growth to identify the respective contributions of E-cadherin, actin, microtubules and FAK. E-cadherin, actin and microtubules drive the first two phases. Microtubules and FAK are involved in the proliferation phase. FAK activity correlates with the metastatic potential of the cells. A robust computational model based on a very large number of experiments reveals the temporal resolution of cell adhesion. Our results provide novel hypotheses to unveil the general mechanisms that contribute to tissue integrity.

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Author:Isabell Smyrek, Biena Mathew Elavunkal, Sabine C. Fischer, Susanna M. Lissek, Sigrun Becker, Ernst H. K. StelzerORCiDGND
URN:urn:nbn:de:hebis:30:3-492845
DOI:https://doi.org/10.1242/bio.037051
ISSN:2046-6390
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/30578251
Parent Title (English):Biology open
Publisher:Company
Place of publication:Cambridge
Document Type:Article
Language:English
Year of Completion:2019
Date of first Publication:2019/01/24
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2019/03/05
Tag:Adhesion; Spheroids; Three-dimensional cell culture; Tissue integrity
Volume:8
Issue:1, bio037051
Page Number:11
First Page:1
Last Page:11
Note:
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
HeBIS-PPN:448054019
Institutes:Biowissenschaften / Biowissenschaften
Exzellenzcluster / Exzellenzcluster Makromolekulare Komplexe
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
Sammlungen:Universitätspublikationen
Open-Access-Publikationsfonds:Biowissenschaften
Licence (German):License LogoCreative Commons - Namensnennung 4.0