@article{d436b998d9744a2b9af5db720cb18d7f,
title = "Cancer associated talin point mutations disorganise cell adhesion and migration",
abstract = "Talin-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.",
author = "Latifeh Azizi and Cowell, {Alana R.} and Mykuliak, {Vasyl V.} and Goult, {Benjamin T.} and Paula Turkki and Hyt{\"o}nen, {Vesa P.}",
note = "Funding Information: This research was supported by the Academy of Finland (Grant 290506 to V.P.H. and grant 323021 to V.V.M.), a Biotechnology and Biological Sciences Research Council Grant BB/N007336/1 (B.T.G.) and a Human Frontier Science Program grant RGP00001/2016 (B.T.G.). L.A. received support from the graduate school of Tampere University and the Anu Kirra´s grant foundation. We acknowledge CSC for supercomputing resources and Biocenter Finland for infrastructure support. The authors acknowledge the Biocenter Finland (BF) and Tampere Imaging Facility (TIF) for the services. We thank Prof. Reinhard F{\"a}ssler and Dr Carsten Grashoff (Max Planck Institute of Biochemistry) for help with TLN1−/–TLN2−/– cells; Prof. Michael Sheetz (National University of Singapore) for providing the mouse wildtype talin expression construct. We thank Rolle Rahikainen, Anssi Nurminen and Sampo Kukkurainen (Tampere University) for their support and insights. Ulla Kiiskinen and Niklas K{\"a}hk{\"o}nen (Tampere University) are acknowledged for technical support. Publisher Copyright: {\textcopyright} 2021, The Author(s). Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",
year = "2021",
doi = "10.1038/s41598-020-77911-4",
language = "English",
volume = "11",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",
}
