TY  - JOUR
A1  - Smyrek, Isabell
A1  - Mathew Elavunkal, Biena
A1  - Fischer, Sabine C.
A1  - Lissek, Susanna M.
A1  - Becker, Sigrun
A1  - Stelzer, Ernst H. K.
T1  - E-cadherin, actin, microtubules and FAK dominate different spheroid formation phases and important elements of tissue integrity
T2  - Biology open
N2  - 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.
KW  - Spheroids
KW  - Three-dimensional cell culture
KW  - Adhesion
KW  - Tissue integrity
Y1  - 2019
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/49284
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-492845
SN  - 2046-6390
N1  - 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.
VL  - 8
IS  - 1, bio037051
SP  - 1
EP  - 11
PB  - Company
CY  - Cambridge
ER  -