美国哈佛医学院Shyamala Maheswaran和Daniel A. Haber合作，发现核糖体蛋白表达和翻译的失调会促进乳腺癌转移。该研究2020年2月6日在线发表于国际学术期刊《科学》。
研究人员对源自乳腺癌患者的循环肿瘤细胞（CTC）进行了体内全基因组CRISPR激活筛选，以鉴定在小鼠中促进远处转移的基因。在此筛选中，研究人员鉴定了丰富的核糖体蛋白编码基因和翻译调节因子。RPL15编码核糖体大亚基的一个组分，其过表达促进癌症细胞在多个器官的转移性生长，并选择性增强了其他核糖体蛋白和细胞周期调节因子的翻译。对来自乳腺癌患者新分离出的CTCs 进行RNA测序,研究人员发现一个具有强核糖体和蛋白质合成特征的亚组。这些CTCs表达增殖和上皮细胞的标志物，并与临床的不良预后相关。 针对这群恶化的CTC细胞的治疗可作为转移进程潜在抑制剂进行研究。
据了解，CTCs从原发肿瘤脱落进入血液，但只有一小部分会发生转移。
附：英文原文
Title: Deregulation of ribosomal protein expression and translation promotes breast cancer metastasis
Author: Richard Y. Ebright, Sooncheol Lee, Ben S. Wittner, Kira L. Niederhoffer, Benjamin T. Nicholson, Aditya Bardia, Samuel Truesdell, Devon F. Wiley, Benjamin Wesley, Selena Li, Andy Mai, Nicola Aceto, Nicole Vincent-Jordan, Annamaria Szabolcs, Brian Chirn, Johannes Kreuzer, Valentine Comaills, Mark Kalinich, Wilhelm Haas, David T. Ting, Mehmet Toner, Shobha Vasudevan, Daniel A. Haber, Shyamala Maheswaran, Douglas S. Micalizzi
Issue&Volume: 2020/02/06
Abstract: AbstractCirculating tumor cells (CTCs) are shed into the bloodstream from primary tumors, but only a small subset generates metastases. We conducted an in vivo genome-wide CRISPR activation screen in breast cancer patient-derived CTCs to identify genes that promote their distant metastasis in mice. Genes coding for ribosomal proteins and regulators of translation were enriched in this screen. Overexpression of RPL15, which encodes a component of the large ribosomal subunit, increased metastatic growth in multiple organs and selectively enhanced translation of other ribosomal proteins and cell cycle regulators. RNA-sequencing of freshly-isolated CTCs from breast cancer patients revealed a subset with strong ribosome and protein synthesis signatures; these CTCs expressed proliferation and epithelial markers and correlated with poor clinical outcome. Therapies targeting this aggressive subset of CTCs may merit exploration as potential suppressors of metastatic progression.
DOI: 10.1126/science.aay0939
Source: https://science.sciencemag.org/content/early/2020/02/05/science.aay0939