小柯机器人

PIK3CA变体在神经胶质瘤形成过程中选择性引发脑活动亢进
2020-02-10 09:48

美国贝勒医学院Benjamin Deneen研究小组发现,PIK3CA变体在神经胶质瘤形成过程中选择性引发脑活动亢进。相关论文于2020年1月29日在线发表于国际学术期刊《自然》。

研究人员使用胶质母细胞瘤小鼠模型,开发了高通量的体内筛选平台,并发现了PIK3CA的几种驱动程序变体。研究人员表明,由这些变体驱动的肿瘤具有不同的分子特性,表现为对脑过度兴奋性的选择性启动和突触组成的重塑。此外,Glypican(GPC)家族的分泌成员在这些肿瘤中选择性表达,而GPC3驱动神经胶质瘤发生和过度兴奋。总之,这项研究表明了功能性研究个体产生的不同肿瘤表型的重要性,并揭示了胶质母细胞瘤如何改变神经元微环境。
 
据介绍,胶质母细胞瘤是一种广泛致死的脑癌,表现出一系列病理生理表型,其中许多是通过与神经元微环境的相互作用而介导的。最近的研究表明,神经元活性的增加在胶质母细胞瘤的增殖和进展中起着重要的作用。胶质母细胞瘤和神经元之间是否存在相互干扰的问题仍然不清楚,因为这些肿瘤如何重塑神经元环境以增强活性的机制尚不清楚。
 
附:英文原文

Title: PIK3CA variants selectively initiate brain hyperactivity during gliomagenesis

Author: Kwanha Yu, Chia-Ching John Lin, Asante Hatcher, Brittney Lozzi, Kathleen Kong, Emmet Huang-Hobbs, Yi-Ting Cheng, Vivek B. Beechar, Wenyi Zhu, Yiqun Zhang, Fengju Chen, Gordon B. Mills, Carrie A. Mohila, Chad J. Creighton, Jeffrey L. Noebels, Kenneth L. Scott, Benjamin Deneen

Issue&Volume: 2020-01-29

Abstract: Glioblastoma is a universally lethal form of brain cancer that exhibits an array of pathophysiological phenotypes, many of which are mediated by interactions with the neuronal microenvironment1,2. Recent studies have shown that increases in neuronal activity have an important role in the proliferation and progression of glioblastoma3,4. Whether there is reciprocal crosstalk between glioblastoma and neurons remains poorly defined, as the mechanisms that underlie how these tumours remodel the neuronal milieu towards increased activity are unknown. Here, using a native mouse model of glioblastoma, we develop a high-throughput in vivo screening platform and discover several driver variants of PIK3CA. We show that tumours driven by these variants have divergent molecular properties that manifest in selective initiation of brain hyperexcitability and remodelling of the synaptic constituency. Furthermore, secreted members of the glypican (GPC) family are selectively expressed in these tumours, and GPC3 drives gliomagenesis and hyperexcitability. Together, our studies illustrate the importance of functionally interrogating diverse tumour phenotypes driven by individual, yet related, variants and reveal how glioblastoma alters the neuronal microenvironment.

DOI: 10.1038/s41586-020-1952-2

Source: https://www.nature.com/articles/s41586-020-1952-2

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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