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. Science, this issue p. 1468; see also p. 1424 Circulating breast cancer cells that overexpress certain ribosomal proteins show enhanced metastatic potential in mice. 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.

中文翻译：

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核糖体蛋白表达和翻译的失调促进乳腺癌转移

转移：翻译问题？实体瘤会将少量癌细胞释放到血流中，据信其中一些会导致转移。赋予这些循环肿瘤细胞 (CTC) 转移潜能的分子特征知之甚少。埃布赖特等人。研究了来自乳腺癌患者的 CTC，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大的转移能力（参见 Ma 和 Jeffrey 的观点）。与这一发现一致，该 CTC 子集水平较高的患者往往预后较差。科学，这个问题 p。1468; 另见第 1424 过度表达某些核糖体蛋白的循环乳腺癌细胞在小鼠中显示出增强的转移潜力。循环肿瘤细胞 (CTC) 从原发性肿瘤流入血流，但这些细胞中只有一小部分会产生转移瘤。我们在来自乳腺癌患者的 CTC 中进行了体内全基因组 CRISPR 激活筛选，以确定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该筛选中得到了丰富。RPL15 的过度表达，它编码大核糖体亚基的一个组成部分，增加了多个器官的转移性生长，并选择性地增强了其他核糖体蛋白和细胞周期调节剂的翻译。来自乳腺癌患者的新鲜分离的 CTC 的 RNA 测序揭示了一个具有强核糖体和蛋白质合成特征的子集；这些 CTC 表达增殖和上皮标志物，并与较差的临床结果相关。