Author:
Azizi Latifeh,Cowell Alana R.,Mykuliak Vasyl V.,Goult Benjamin T.,Turkki Paula,Hytönen Vesa P.
Abstract
AbstractTalin-1 is a key component of the multiprotein adhesion complexes which mediate cell migration, adhesion and integrin signalling and has been linked to cancer in several studies. We analysed talin-1 mutations reported in the Catalogue of Somatic Mutations in Cancer database and developed a bioinformatics pipeline to predict the severity of each mutation. These predictions were then assessed using biochemistry and cell biology experiments. With this approach we were able to identify several talin-1 mutations affecting integrin activity, actin recruitment and Deleted in Liver Cancer 1 localization. We explored potential changes in talin-1 signalling responses by assessing impact on migration, invasion and proliferation. Altogether, this study describes a pipeline approach of experiments for crude characterization of talin-1 mutants in order to evaluate their functional effects and potential pathogenicity. Our findings suggest that cancer related point mutations in talin-1 can affect cell behaviour and so may contribute to cancer progression.
Funder
Anu Kirra Foundation
Academy of Finland
Biotechnology and Biological Sciences Research Council
Human Frontier Science Program
Publisher
Springer Science and Business Media LLC
Reference76 articles.
1. Lu, P., Weaver, V. M. & Werb, Z. The extracellular matrix: A dynamic niche in cancer progression. J. Cell. Biol. 196, 395–406 (2012).
2. Goult, B. T. et al. Structural studies on full-length talin1 reveal a compact auto-inhibited dimer: Implications for talin activation. J. Struct. Biol. 184, 21–32 (2013).
3. Anthis, N. J. et al. The structure of an integrin/talin complex reveals the basis of inside-out signal transduction. EMBO J. 28, 3623–3632 (2009).
4. Tanentzapf, G. & Brown, N. H. An interaction between integrin and the talin FERM domain mediates integrin activation but not linkage to the cytoskeleton. Nat. Cell Biol. 8, 601–606 (2006).
5. Hemmings, L. et al. Talin contains three actin-binding sites each of which is adjacent to a vinculin-binding site. J. Cell. Sci. 109(Pt 11), 2715–2726 (1996).
Cited by
17 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献