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。

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