文章：

核糖体蛋白表达和翻译的失调促进乳腺癌转移

Deregulation of ribosomal protein expression and translation promotes breast cancer metastasis

原文发布日期：2020-02-06

DOI: 10.1126/science.aay0939

类型: Report

开放获取: 否

文章简介：

Metastasis: A matter of translation?

Solid tumors shed a small number of cancer cells into the bloodstream, some of which are believed to contribute to metastasis. The molecular features that confer these circulating tumor cells (CTCs) with metastatic potential are poorly understood. Ebright et al. studied CTCs from breast cancer patients and found that cells with increased expression levels of certain ribosomal proteins and regulators of translation had greater metastatic capacity in a mouse model (see the Perspective by Ma and Jeffrey). Consistent with this finding, patients with higher levels of this subset of CTCs tended to have a poorer prognosis.

Abstract

Circulating tumor cells (CTCs) are shed into the bloodstream from primary tumors, but only a small subset of these cells generates metastases. We conducted an in vivo genome-wide CRISPR activation screen in CTCs from breast cancer patients to identify genes that promote 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.

简介翻译： 

转移：翻译的问题？

实体肿瘤会将少量癌细胞释放到血液中，其中一些被认为有助于转移。赋予这些循环肿瘤细胞（CTC）转移潜能的分子特征尚不清楚。Ebright等人研究了乳腺癌患者的循环肿瘤细胞，发现某些核糖体蛋白和翻译调节因子表达水平升高的细胞在小鼠模型中具有更强的转移能力（参见Ma和Jeffrey的观点）。与这一发现一致，具有更高水平这类循环肿瘤细胞亚群的患者往往预后较差。

摘要

循环肿瘤细胞从原发性肿瘤脱落进入血液，但这些细胞中只有一小部分会产生转移。我们对乳腺癌患者的循环肿瘤细胞进行了体内全基因组CRISPR激活筛选，以识别促进小鼠远处转移的基因。编码核糖体蛋白和翻译调节因子的基因在此筛选中富集。过表达RPL15（编码大核糖体亚基的一个组分）可增加多个器官的转移生长，并选择性地增强其他核糖体蛋白和细胞周期调节因子的翻译。对新鲜分离的乳腺癌患者循环肿瘤细胞进行RNA测序，揭示了一个具有强核糖体和蛋白质合成特征的亚群；这些循环肿瘤细胞表达增殖和上皮标记，并与不良临床结果相关。针对这一侵袭性循环肿瘤细胞亚群的疗法可能值得探索，作为转移进展的潜在抑制手段。

原文链接：

Deregulation of ribosomal protein expression and translation promotes breast cancer metastasis