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.
Author: | Isabell SmyrekGND, Biena Mathew ElavunkalGND, Sabine C. FischerORCiD, Susanna M. LissekORCiD, 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): | Creative Commons - Namensnennung 4.0 |