BioMediTech, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
School of Biosciences, University of Kent, Canterbury, CT2 7NJ, Kent, UK.
Sci Rep. 2021 Jan 11;11(1):347. doi: 10.1038/s41598-020-77911-4.
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.
塔林-1 是介导细胞迁移、黏附和整合素信号的多蛋白黏附复合物的关键组成部分，在几项研究中与癌症有关。我们分析了癌症体细胞突变目录数据库中报告的塔林-1 突变，并开发了一种生物信息学管道来预测每个突变的严重程度。然后使用生物化学和细胞生物学实验来评估这些预测。通过这种方法，我们能够识别出几种影响整合素活性、肌动蛋白募集和肝癌缺失蛋白 1 定位的塔林-1 突变。我们通过评估对迁移、侵袭和增殖的影响，探索了塔林-1 信号转导反应的潜在变化。总的来说，这项研究描述了一种用于粗化塔林-1 突变体功能特征的实验管道方法，以评估它们的功能影响和潜在的致病性。我们的发现表明，塔林-1 中的癌症相关点突变可能会影响细胞行为，从而可能促进癌症的进展。
