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组蛋白变体的掺入促进肿瘤转移
作者:小柯机器人 发布时间:2019/9/29 14:32:40

美国威尔康奈尔医学院John Blenis和Ana P. Gomes等研究人员合作发现,组蛋白H3变体动态整合到染色质中对于获取侵略性特征和转移性定植至关重要。2019年9月26日,国际知名学术期刊《癌细胞》在线发表了这一成果。

研究人员发现引起转移的途径调节组蛋白分子伴侣以减少经典组蛋白掺入染色质中,从而引起预后不良基因和转移诱导转录因子启动子处的H3.3变体沉积。H3.3向染色质的这种特殊掺入对于诱导侵袭性特征(促进转移形成)既必要又充分。总之,这些数据清楚地表明,将组蛋白变体H3.3掺入染色质中是肿瘤发生过程中细胞命运的主要调节者,并将组蛋白分子伴侣定义为有价值的浸润性癌治疗靶标。

据介绍,转移是癌症死亡的主要原因。染色质重塑为驱动转移所必需的细胞重编程提供了基础。但是,对于这种重塑的性质及其调节知之甚少。

附:英文原文

Title: Dynamic Incorporation of Histone H3 Variants into Chromatin Is Essential for Acquisition of Aggressive Traits and Metastatic Colonization

Author: Ana P. Gomes, Didem Ilter, Vivien Low, Adam Rosenzweig, Zih-Jie Shen, Tanya Schild, Martin A. Rivas, Ekrem E. Er, Dylan R. McNally, Anders P. Mutvei, Julie Han, Yi-Hung Ou, Paola Cavaliere, Edouard Mullarky, Michal Nagiec, Sejeong Shin, Sang-Oh Yoon, Noah Dephoure, Joan Massagué, Ari M. Melnick, Lewis C. Cantley, Jessica K. Tyler, John Blenis

Issue&Volume: 26 September 2019

Abstract: 

Metastasis is the leading cause of cancer mortality. Chromatin remodeling provides the foundation for the cellular reprogramming necessary to drive metastasis. However, little is known about the nature of this remodeling and its regulation. Here, we show that metastasis-inducing pathways regulate histone chaperones to reduce canonical histone incorporation into chromatin, triggering deposition of H3.3 variant at the promoters of poor-prognosis genes and metastasis-inducing transcription factors. This specific incorporation of H3.3 into chromatin is both necessary and sufficient for the induction of aggressive traits that allow for metastasis formation. Together, our data clearly show incorporation of histone variant H3.3 into chromatin as a major regulator of cell fate during tumorigenesis, and histone chaperones as valuable therapeutic targets for invasive carcinomas.

DOI: 10.1016/j.ccell.2019.08.006

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(19)30374-5

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