Cancer associated talin point mutations disorganise cell adhesion and migration.

Azizi, Latifeh, Cowell, Alana R, Mykuliak, Vasyl V ORCID: 0000-0002-2522-9907, Goult, Benjamin T ORCID: 0000-0002-3438-2807, Turkki, Paula and Hytönen, Vesa P ORCID: 0000-0002-9357-1480 (2021) Cancer associated talin point mutations disorganise cell adhesion and migration. Scientific reports, 11 (1). 347-.

PDF
2021_Azizi_SciReps.pdf - Open Access published version
Download (8MB) | Preview

Official URL: http://dx.doi.org/10.1038/s41598-020-77911-4

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.

Item Type:	Article
Uncontrolled Keywords:	Humans, Neoplasms, Talin, Computational Biology, Cell Adhesion, Cell Movement, Point Mutation, Databases, Genetic
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:	13 Mar 2024 09:59
DOI:	10.1038/s41598-020-77911-4
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3179310