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通过 MigExpress 对迁移因子进行系统分析,确定了非小细胞肺癌中细胞迁移控制的关键基因。

Systematic analysis of migration factors by MigExpress identifies essential cell migration control genes in non-small cell lung cancer.

机构信息

Division of Cancer Research, Department of Thoracic Surgery, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, German Cancer Consortium (DKTK) - Partner Site Freiburg, Germany.

Division of RNA Biology & Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany.

出版信息

Mol Oncol. 2021 Jul;15(7):1797-1817. doi: 10.1002/1878-0261.12973. Epub 2021 May 14.

Abstract

Cell migration is an essential process in health and in disease, including cancer metastasis. A comprehensive inventory of migration factors is nonetheless lacking-in part due to the difficulty in assessing migration using high-throughput technologies. Hence, there are currently very few screens that systematically reveal factors controlling cell migration. Here, we introduce MigExpress as a platform for the 'identification of Migration control genes by differential Expression'. MigExpress exploits the combination of in-depth molecular profiling and the robust quantitative analysis of migration capacity in a broad panel of samples and identifies migration-associated genes by their differential expression in slow- versus fast-migrating cells. We applied MigExpress to investigate non-small cell lung cancer (NSCLC), which is the most frequent cause of cancer mortality mainly due to metastasis. In 54 NSCLC cell lines, we comprehensively determined mRNA and protein expression. Correlating the transcriptome and proteome profiles with the quantified migration properties led to the discovery and validation of FLNC, DSE, CPA4, TUBB6, and BICC1 as migration control factors in NSCLC cells, which were also negatively correlated with patient survival. Notably, FLNC was the least expressed filamin in NSCLC, but the only one controlling cell migration and correlating with patient survival and metastatic disease stage. In our study, we present MigExpress as a new method for the systematic analysis of migration factors and provide a comprehensive resource of transcriptomic and proteomic data of NSCLC cell lines related to cell migration.

摘要

细胞迁移是健康和疾病(包括癌症转移)中的一个基本过程。然而,由于使用高通量技术评估迁移的难度,全面的迁移因子清单仍然缺乏。因此,目前很少有能够系统地揭示控制细胞迁移的因素的筛选方法。在这里,我们介绍了 MigExpress,这是一种用于“通过差异表达鉴定迁移控制基因”的平台。MigExpress 利用深入的分子谱分析与广泛样本中迁移能力的稳健定量分析相结合,通过慢迁移细胞与快迁移细胞之间的差异表达来鉴定与迁移相关的基因。我们应用 MigExpress 研究非小细胞肺癌 (NSCLC),这是癌症死亡率最高的主要原因,主要是由于转移。在 54 种 NSCLC 细胞系中,我们全面测定了 mRNA 和蛋白质表达。将转录组和蛋白质组谱与量化的迁移特性相关联,导致发现并验证了 FLNC、DSE、CPA4、TUBB6 和 BICC1 是 NSCLC 细胞中的迁移控制因素,这些因素与患者生存呈负相关。值得注意的是,FLNC 是非小细胞肺癌中表达最少的细丝蛋白,但它是唯一控制细胞迁移并与患者生存和转移性疾病阶段相关的蛋白。在我们的研究中,我们提出了 MigExpress 作为一种系统分析迁移因子的新方法,并提供了与 NSCLC 细胞迁移相关的转录组和蛋白质组数据的全面资源。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a94c/8253088/18f3ed7c69f0/MOL2-15-1797-g004.jpg

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