Schmidt, A., Kaakinen, M., Wenta, T., & Manninen, A. (2022). Loss of α6β4 integrin-mediated hemidesmosomes promotes prostate epithelial cell migration by stimulating focal adhesion dynamics. Frontiers in Cell and Developmental Biology, 10, 886569. https://doi.org/10.3389/fcell.2022.886569
Loss of α6β4 integrin-mediated hemidesmosomes promotes prostate epithelial cell migration by stimulating focal adhesion dynamics
|Author:||Schmidt, Anette1; Kaakinen, Mika2; Wenta, Tomasz1,3;|
1Disease Networks Research Unit, Faculty of Biochemistry and Molecular Medicine, Biocenter Oulu, University of Oulu, Oulu, Finland
2Oulu Center for Cell-Matrix Research, Faculty of Biochemistry and Molecular Medicine, Biocenter Oulu, University of Oulu, Oulu, Finland
3Department of General and Medical Biochemistry, Faculty of Biology, University of Gdansk, Gdansk, Poland
|Online Access:||PDF Full Text (PDF, 3.5 MB)|
|Persistent link:|| http://urn.fi/urn:nbn:fi-fe2023031531753
|Publish Date:|| 2023-03-15
Epithelial cell adhesion is mediated by actin cytoskeleton-linked focal adhesions (FAs) and intermediate filament-associated hemidesmosomes (HDs). HDs are formed by α6β4-integrins and mediate stable anchoring to the extracellular matrix (ECM) while FAs containing β1-integrins regulate cell migration. Loss of HDs has been reported in various cancers such as prostate cancer where it correlates with increased invasive migration. Here we have studied cell migration properties and FA dynamics in genetically engineered prostate epithelial cell lines with intact or disrupted HDs. Disruption of HDs by depleting α6- or β4-integrin expression promoted collective cell migration and modulated migratory activity. Dynamic analysis of fluorescent protein-tagged FA marker proteins revealed faster FA assembly and disassembly kinetics in HD-depleted cells. FRAP analysis showed that loss of HDs correlated with faster diffusion rates of focal adhesion kinase (FAK) and vinculin in and out of FAs. These data suggest that loss of α6β4-mediated HDs promote cell migration and FA assembly dynamics by influencing the molecular diffusion rates of FAK.
Frontiers in cell and developmental biology
|Type of Publication:||
A1 Journal article – refereed
|Field of Science:||
1182 Biochemistry, cell and molecular biology
This work was funded by Jane and Aatos Erkko Foundation (190046; AM) and by University of Oulu and Academy of Finland PROFI3 program (AM).
© 2022 Schmidt, Kaakinen, Wenta and Manninen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.