研究提供了更好的如何脑瘤“喂”的理解

New findings explain how the enzyme ACSS2 aids tumors in a nutrient-starved environment offering potential new treatment approaches

MD安德森新闻发布2017年5月25日

All cancer tumors have one thing in common – they must feed themselves to grow and spread, a difficult feat since they are usually in a tumor microenvironment with limited nutrients and oxygen. A study at德克萨斯大学的MD AndersonCancer Center已经透露了所谓的乙酰辅酶A的酶是如何合成2（ACSS2）新的细节允许，尽管他们的恶劣环境中的脑肿瘤生长。这项研究结果发表在5月25日网上发行分子细胞, portends ACSS2 as a potential player in new approaches to treating this often deadly disease.

ACSS2提供肿瘤通过提高其使用称为乙蜂窝盐作为基于碳的食物来源，而不是更理想葡萄糖这通常是在癌细胞中的供不应求的能力的竞争优势。这条生命线使肿瘤细胞在肿瘤的核心生存和发展，甚至因为它与营养缺乏战斗。

Current therapies and the body’s own immune system are not efficient at stopping this vital nutrient pathway in cancer cells, and little is known about how these life-giving proteins are transported from cytosol, a liquid cell component, into the nucleus via a process called nuclear translocation. The ability to halt nuclear translocation of ACSS2 would cut off the cancer cell’s self-maintaining ability at its most basic level. The study, led byZhimin Lu, M.D., Ph.D., professor ofNeuro-Oncology，提供了有关核转及如何ACSS2可以提供治疗的新途径新信息。

“Overcoming metabolic stress is a critical step in solid tumor growth. Acetyl coenzyme A (CoA) generated via glucose and acetate uptake is a key carbon source for important cellular processes such as histone acetylation and gene expression,” said Lu. “However, how acetyl CoA is produced under nutritional stress is unclear. Our study explains the underlying mechanics of how this occurs, with ACSS2 as a novel and important method for gene expression under these circumstances.”

Using a CRISPR gene editing process, Lu’s team revealed what roles ACSS2 plays in histone acetylation by generation of nuclear acetyl-CoA from acetate within the cell’s nucleus. It also demonstrated the significance of histone modification via a metabolic enzyme in maintaining cell stability and tumor development. Histones are proteins that act as spools around which DNA winds and are crucial to gene regulation, while histone acetylation is a modification process critical to gene expression.

在本质上，ACSS2给出用于生产充当细胞的废物处理系统，从而摆脱不需要的物质的细胞溶酶体，细胞结构的遗传许可，同时回收消化的产品为蛋白质，DNA和脂质合成。溶酶体被认为是肿瘤发展的一个因素。ACSS2也促进叫做自噬细胞吃人的进给机构，使溶酶体接受，消化，循环和急需的营养物质。当位于细胞外的营养物质是有限的，是ACSS2通过增加自噬和重用溶酶体消化产物从细胞存活和生长不需要的或存储材料能够再编程癌细胞代谢。

“These findings elucidate an instrumental interplay between reprogramming of metabolism and gene expression in cancer cells,” said Lu. “Inhibition of both ACSS2’s nuclear function and the metabolic pathway known as glycolysis, which converts glucose to tumor-feeding energy, appears to be an efficient approach for cancer treatment.”

MD安德森研究小组成员包乐动体育LDsports中国括新建李，博士，徐谦，博士，夏炎，博士，燕化郑博士和钟浩利，博士，一切神经肿瘤的;和Ganesh饶，医学博士，神经外科。其他参与的机构包括杜克 - 新加坡国立大学内侧学院，新加坡;温州医学院，温州，中国;青岛大学癌症研究所，青岛，中国;和圣中山大学肿瘤防治中心，广州，中国。

这项研究是由美国国立卫生研究院（CA109035，CA169603，CA204996，NS089754，CA016672和CA127001）资助;詹姆斯·麦克唐纳基金会21st世纪科学举措脑癌研究奖（220020318）;乐动体育LDsports中国中国国家自然科学基金（8167282和81472386）;在MD安德森奥德赛奖学金;安妮伊斯特兰矛研究金在GI癌症研究;乐动体育LDsports中国卡罗琳·罗斯被资助的奖学金;和哈罗德C.和Mary L.日常捐赠基金奖学金。卢是一个Ruby E.卢瑟福特聘教授。