Contributions of talin-1 to glioma cell–matrix tensional homeostasis
- 7 December 2011
- journal article
- research article
- Published by The Royal Society in Journal of The Royal Society Interface
- Vol. 9 (71), 1311-1317
- https://doi.org/10.1098/rsif.2011.0567
Abstract
The ability of cells to adapt their mechanical properties to those of the surrounding microenvironment (tensional homeostasis) has been implicated in the progression of a variety of solid tumours, including the brain tumour glioblastoma multiforme (GBM). GBM tumour cells are highly sensitive to extracellular matrix (ECM) stiffness and overexpress a variety of focal adhesion proteins, such as talin. While talin has been shown to play critical early roles in integrin-based force-sensing in non-tumour cells, it remains unclear whether this protein contributes to tensional homeostasis in GBM cells. Here, we investigate the role of the talin isoform talin-1 in enabling human GBM cells to adapt to ECM stiffness. We show that human GBM cells express talin-1, and we use RNA interference to suppress talin-1 expression without affecting levels of talin-2, vinculin or phosphorylated focal adhesion kinase. Knockdown of talin-1 strongly reduces both cell spreading area and random migration speed but does not significantly affect overall focal adhesion size distributions. Most strikingly, atomic force microscopy indentation reveals that talin-1 suppression compromises adaptation of cell stiffness to changes in ECM stiffness. Together, these data support a role for talin-1 in the maintenance of tensional homeostasis in GBM and suggest a functional role for enriched talin expression in this tumour.Keywords
This publication has 46 references indexed in Scilit:
- Nanoscale architecture of integrin-based cell adhesionsNature, 2010
- Studies on the morphology and spreading of human endothelial cells define key inter- and intramolecular interactions for talin1European Journal of Cell Biology, 2010
- Matrix Crosslinking Forces Tumor Progression by Enhancing Integrin SignalingCell, 2009
- The heel and toe of the cell's foot: A multifaceted approach for understanding the structure and dynamics of focal adhesionsCell Motility, 2009
- Absence of Filamin A Prevents Cells from Responding to Stiffness Gradients on Gels Coated with Collagen but not FibronectinBiophysical Journal, 2009
- Cell–Matrix De-Adhesion Dynamics Reflect Contractile MechanicsCellular and Molecular Bioengineering, 2009
- Biomechanics: Cell Research and Applications for the Next DecadeAnnals of Biomedical Engineering, 2009
- Mechanics, malignancy, and metastasis: The force journey of a tumor cellCancer and Metastasis Reviews, 2009
- Mechanotransduction in development: a growing role for contractilityNature Reviews Molecular Cell Biology, 2009
- Talin depletion reveals independence of initial cell spreading from integrin activation and tractionNature, 2008