Cancer associated talin point mutations disorganise cell adhesion and migration

Azizi, L.; Cowell, A.; Mykuliak, V. V.; Goult, B. T.; Turkki, P.; Hytonen, V. P.

doi:10.1101/2020.03.25.008193

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bioRxiv · 10.1101/2020.03.25.008193

Cancer associated talin point mutations disorganise cell adhesion and migration

Azizi, L.·Cowell, A.·Mykuliak, V. V.·Goult, B. T.·Turkki, P.·Hytonen, V. P.

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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 COSMIC (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.

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Azizi, L., Cowell, A., Mykuliak, V. V., Goult, B. T., Turkki, P., Hytonen, V. P.. 2020-03-26. Cancer associated talin point mutations disorganise cell adhesion and migration. https://doi.org/10.1101/2020.03.25.008193

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