MigExpress discovers essential cell migration control genes in non-small cell lung cancer

Cell migration is an essential process in health and disease - especially in cancer metastasis. The difficulty to assess migration in high throughput presents a methodological hurdle - hence, only very few screens revealed factors controlling this important process. 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 slowly versus fast migrating cells. We applied MigExpress to non-small cell lung cancer (NSCLC), 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 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.细胞迁移（Cell Migration）是维持机体健康与参与疾病发生发展的核心生物学过程，尤其在癌症转移中发挥关键作用。高通量条件下评估细胞迁移始终存在技术瓶颈，这成为该领域的方法学障碍，因此目前仅有极少数筛选研究揭示了调控这一关键过程的相关因子。本研究推出MigExpress平台，其全称为"基于差异表达的迁移调控基因鉴定平台（Identification of Migration Control Genes by Differential Expression）"。MigExpress平台整合了深度分子谱分析与对大规模样本队列中细胞迁移能力的稳健定量分析，并通过比较快速与慢速迁移细胞间的差异表达基因，筛选得到与细胞迁移相关的调控因子。本研究将MigExpress平台应用于非小细胞肺癌（non-small cell lung cancer, NSCLC）——这一主要因转移导致癌症相关死亡的最常见恶性肿瘤。研究团队针对54株非小细胞肺癌细胞系，全面检测了其mRNA与蛋白质表达谱。将转录组与蛋白质组表达谱与定量得到的细胞迁移特性进行关联分析后，研究团队成功鉴定并验证了FLNC、DSE、CPA4、TUBB6与BICC1作为非小细胞肺癌细胞的迁移调控因子，且这些因子的表达水平与患者生存率呈负相关。值得注意的是，FLNC是非小细胞肺癌中表达量最低的细丝蛋白家族成员，却是唯一能够调控细胞迁移、且与患者生存率及肿瘤转移分期显著相关的细丝蛋白。