MTSS1 is a metastasis driver in a subset of human melanomas
MTSS1 is a metastasis driver in a subset of human melanomas
复制标题
DOI：
10.1038/ncomms4465
复制
发表时间：
2014-03-01
影响因子：
16.6
通讯作者：
Wagner, Stephan N.
中科院分区：
文献类型：
--
作者：
Mertz, Kirsten D.;Pathria, Gaurav;Wagner, Stephan N.
在基因组高度改变的癌症中，不同的基因改变驱动亚群，而不是大多数个体肿瘤。在这里，我们对人类肿瘤样本进行序列搜索，寻找与患者生存相关的基因拷贝数变异的转录异常数据点，以识别具有前侵入功能的基因。利用体外和体内功能的丧失和获得方法，我们发现其中一个这样的基因MTSS1促进黑素细胞转移的能力，并在这一过程中通过Rho-GTPases和cofilin参与肌动蛋白动力学。事实上，MTSS1高表达定义了预后不良的原发性黑色素瘤亚组。这些数据强调了分子亚群在遗传复杂癌症中的生物学、临床和潜在治疗意义。
In cancers with a highly altered genome, distinct genetic alterations drive subsets rather than the majority of individual tumours. Here we use a sequential search across human tumour samples for transcript outlier data points with associated gene copy number variations that correlate with patient's survival to identify genes with pro-invasive functionality. Employing loss and gain of function approaches in vitro and in vivo, we show that one such gene, MTSS1, promotes the ability of melanocytic cells to metastasize and engages actin dynamics via Rho-GTPases and cofilin in this process. Indeed, high MTSS1 expression defines a subgroup of primary melanomas with unfavourable prognosis. These data underscore the biological, clinical and potential therapeutic implications of molecular subsets within genetically complex cancers.