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YTHDF3通过引发m6A丰富转录本的翻译来促进乳腺癌脑转移
作者:小柯机器人 发布时间:2020/10/31 21:39:37

近日,美国德克萨斯大学MD安德森癌症中心Suyun Huang、芝加哥大学何川等研究人合作发现,YTHDF3通过引发m6A丰富转录本的翻译来促进乳腺癌脑转移。该项研究成果于2020年10月29日在线发表在《癌细胞》杂志上。

研究人员显示YTHDF3过表达在临床上与乳腺癌患者的脑转移相关。YTHDF3促进癌细胞与脑内皮细胞和星形胶质细胞的相互作用、血脑屏障的外渗、血管生成和生长。从机制上讲,YTHDF3增强了ST6GALNAC5、GJA1和EGFR的m6A富集转录本的翻译,这些转录本均与脑转移有关。
 
此外,YTHDF3在脑转移瘤中的过表达是由于基因拷贝数的增加和YTHDF3帽非依赖性翻译的自动调节,其方式是与其自身5'UTR中的m6A残基结合。这项工作揭示了YTHDF3在控制癌细胞与脑微环境之间的相互作用中的重要作用,从而诱发脑转移。
 
据了解,脑转移是癌症死亡的主要原因,但其分子机制却少有研究。另外,关于m6A阅读蛋白YTHDF3在人类疾病中的作用还知之甚少。
 
附:英文原文

Title: YTHDF3 Induces the Translation of m6A-Enriched Gene Transcripts to Promote Breast Cancer Brain Metastasis

Author: Guoqiang Chang, Lei Shi, Youqiong Ye, Hailing Shi, Lixian Zeng, Shweta Tiwary, Jason T. Huse, Lei Huo, Li Ma, Yongjie Ma, Sicong Zhang, Jianwei Zhu, Victoria Xie, Peng Li, Leng Han, Chuan He, Suyun Huang

Issue&Volume: 2020-10-29

Abstract: Brain metastasis is a major cause of cancer mortality, but its molecular mechanisms are severely understudied. In addition, little is known regarding the role of m6A reader YTHDF3 in human diseases. Here, we show that YTHDF3 overexpression clinicallycorrelates with brain metastases in breast cancer patients. YTHDF3 promotes cancercell interactions with brain endothelial cells and astrocytes, blood-brain barrierextravasation, angiogenesis, and outgrow. Mechanistically, YTHDF3 enhances the translationof m6A-enriched transcripts for ST6GALNAC5, GJA1, and EGFR, all associated with brain metastasis.Furthermore, overexpression of YTHDF3 in brain metastases is attributed to increasedgene copy number and the autoregulation of YTHDF3 cap-independent translation by bindingto m6A residues within its own 5′ UTR. Our work uncovers an essential role of YTHDF3 incontrolling the interaction between cancer cells and brain microenvironment, thereby inducing brain metastatic competence.

DOI: 10.1016/j.ccell.2020.10.004

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(20)30498-0

期刊信息

Cancer Cell:《癌细胞》,创刊于2002年。隶属于细胞出版社,最新IF:23.916
官方网址:https://www.cell.com/cancer-cell/home
投稿链接:https://www.editorialmanager.com/cancer-cell/default.aspx