title: Contributions of talin-1 to glioma cell-matrix tensional homeostasis.
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.
authors.affiliation: Department of Bioengineering, University of California, 274A Stanley Hall no. 1762, Berkeley, CA 94720, USA.
authors.forename: Shamik
authors.initials: S
authors.lastname: Sen
authors.forename: Win Pin
authors.initials: WP
authors.lastname: Ng
authors.forename: Sanjay
authors.initials: S
authors.lastname: Kumar
mesh_terms: D045744:Cell Line, Tumor; D005109:Extracellular Matrix; D005910:Glioma / Q000503:physiopathology*; D006706:Homeostasis; D006801:Humans; D040542:Mechanotransduction, Cellular; D013314:Stress, Mechanical; D016608:Talin / Q000378:metabolism*; D013718:Tensile Strength
chemical_list: C518832:TLN1 protein, human; D016608:Talin