Cancer associated talin point mutations disorganise cell adhesion and migration

Cancer associated talin point mutations disorganise cell adhesion and migration
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癌症相关的talin点突变扰乱细胞粘附和迁移

DOI:
10.1101/2020.03.25.008193
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发表时间:
2020
期刊:
--
影响因子:
--
通讯作者:
Azizi L
Azizi L
中科院分区:
--
文献类型:
--
作者:
Azizi L

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Talin-1是介导细胞迁移、粘附和整合素信号传导的多蛋白粘附复合物的关键组分,并且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talin-1突变,并开发了一个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评估这些预测。通过这种方法,我们能够识别几个talin-1突变影响整合素活性,肌动蛋白募集和肝癌1定位。我们通过评估对迁移、侵袭和增殖的影响来探索talin-1信号应答的潜在变化。总之,这项研究描述了一个管道的实验方法,粗表征talin-1突变体,以评估其功能的影响和潜在的致病性。我们的研究结果表明,癌症相关的talin-1点突变可以影响细胞行为,因此可能有助于癌症的进展。
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.
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