Azizi, Latifeh, Cowell, Alana ORCID: 0000-0003-4614-9364, Mykuliak, Vasyl, Goult, Benjamin ORCID: 0000-0002-3438-2807, Turkki, Paula ORCID: 0000-0002-5969-4807 and Hytönen, Vesa ORCID: 0000-0002-9357-1480
(2020)
Cancer associated talin point mutations disorganise cell adhesion and migration.
[Preprint]
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.
Item Type: | Preprint |
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Uncontrolled Keywords: | Cancer, Genetics, Cancer |
Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology |
Depositing User: | Symplectic Admin |
Date Deposited: | 13 Mar 2024 09:59 |
Last Modified: | 15 Mar 2024 20:51 |
DOI: | 10.1101/2020.03.25.008193 |
Open Access URL: | https://doi.org/10.1101/2020.03.25.008193 |
Related URLs: | |
URI: | https://livrepository.liverpool.ac.uk/id/eprint/3179312 |