Featured Research

from universities, journals, and other organizations

'Oncometabolite' linked with widespread alterations in gene expression

Date:
January 18, 2011
Source:
Cell Press
Summary:
New research enhances the understanding of the link between metabolic deregulation and cancer and may help to guide development of new targeted cancer therapies. The new study finds that a metabolite commonly elevated in brain cancer and leukemia may promote tumorigenesis by altering the expression of a large number of genes.

A new study finds that a metabolite commonly elevated in brain cancer and leukemia may promote tumorigenesis by altering the expression of a large number of genes. New research, published by Cell Press in the January 18th issue of the journal Cancer Cell, enhances the understanding of the link between metabolic deregulation and cancer and may help to guide development of new targeted cancer therapies.

Related Articles


More than 75% of low grade gliomas and secondary glioblastoma multiforme (GBM), and about 20% of acute myeloid leukemia (AML), exhibit mutations in genes for isocitrate dehydrogenase (IDH1 and IDH2). The tumor-derived mutations in IDH1 and IDH2 lead to loss of normal production of α-ketoglutarate (α-KG), which is required for over 60 enzymes known as dioxygenases, and a gain in the production of 2-hydroxygulatrate (2-HG), which is found at very low levels in normal cells.

"Although 2-HG has been proposed to be an 'oncometabolite', its mechanism of action is not known," explains senior study author, Dr. Yue Xiong from the University of North Carolina at Chapel Hill. "Previous work demonstrated that 2-HG and α-KG are structurally similar, suggesting that 2-HG might interfere with the ability of α-KG to bind to and activate dioxygenases." Dr. Xiong, co-authors Dr. Kun-Liang Guan from the University of California at San Diego and Dr. Shi-min Zhao from Fudan University in Shanghai, and their colleagues designed a series of experiments to uncover how 2-HG contributes to cancer and determine the functional relationship between α-KG reduction and 2-HG elevation.

The researchers discovered that 2-HG functioned as a competitive inhibitor of multiple α-KG-dependent dioxygenases. Some of these dioxygenases regulate methylation of histones, a group of proteins that contribute to the structural organization of chromatin, and methylation of DNA. Alteration of histone and DNA methylation is likely to have a substantial impact on regulation of gene expression and, quite possibly, promote tumor growth. The researchers also showed that a cell-permeable derivative of α-KG reversed the effects of 2-HG inhibition.

"Our findings support the notion that although D-2-HG may not play a significant role in the regulation of α-KG-dependent dioxygenases in normal cells because of its low level, it could play an important role under pathological conditions in tumor cells expressing mutated IDH1 or IDH2," concludes Dr. Xiong. "We also suggest that drugs mimicking α-KG merit exploration as a therapy for tumors that harbor an IDH1 or IDH2 mutation, either alone or in combination with inhibitors to reduce the 2-HG production."


Story Source:

The above story is based on materials provided by Cell Press. Note: Materials may be edited for content and length.


Journal Reference:

  1. Wei Xu, Hui Yang, Ying Liu, Ying Yang, Ping Wang, Se-Hee Kim, Shinsuke Ito, Chen Yang, Pu Wang, Meng-Tao Xiao, Li-xia Liu, Wen-qing Jiang, Jing Liu, Jin-ye Zhang, Bin Wang, Stephen Frye, Yi Zhang, Yan-hui Xu, Qun-ying Lei, Kun-Liang Guan, Shi-min Zhao, Yue Xiong. Oncometabolite 2-Hydroxyglutarate Is a Competitive Inhibitor of α-Ketoglutarate-Dependent Dioxygenases. Cancer Cell, 2011; 19 (1): 17-30 DOI: 10.1016/j.ccr.2010.12.014

Cite This Page:

Cell Press. "'Oncometabolite' linked with widespread alterations in gene expression." ScienceDaily. ScienceDaily, 18 January 2011. <www.sciencedaily.com/releases/2011/01/110118123558.htm>.
Cell Press. (2011, January 18). 'Oncometabolite' linked with widespread alterations in gene expression. ScienceDaily. Retrieved January 31, 2015 from www.sciencedaily.com/releases/2011/01/110118123558.htm
Cell Press. "'Oncometabolite' linked with widespread alterations in gene expression." ScienceDaily. www.sciencedaily.com/releases/2011/01/110118123558.htm (accessed January 31, 2015).

Share This


More From ScienceDaily



More Health & Medicine News

Saturday, January 31, 2015

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

CDC: Get Vaccinated for Measles

CDC: Get Vaccinated for Measles

Reuters - US Online Video (Jan. 30, 2015) The CDC is urging people to get vaccinated for measles amid an outbreak that began at Disneyland and has now infected more than 90 people. Linda So reports. Video provided by Reuters
Powered by NewsLook.com
Obama To Outline New Plan For Personalized Medicine

Obama To Outline New Plan For Personalized Medicine

Newsy (Jan. 30, 2015) President Obama is expected to speak with drugmakers Friday about his Precision Medicine Initiative first introduced last week. Video provided by Newsy
Powered by NewsLook.com
NFL Concussions Down; Still on Parents' Minds

NFL Concussions Down; Still on Parents' Minds

AP (Jan. 30, 2015) The NFL announced this week that the number of game concussions dropped by a quarter over last season. Still, the dangers of the sport still weigh on players, and parents&apos; minds. (Jan. 30) Video provided by AP
Powered by NewsLook.com
U.S. Wants to Analyze DNA from 1 Million People

U.S. Wants to Analyze DNA from 1 Million People

Reuters - US Online Video (Jan. 30, 2015) The U.S. has proposed analyzing genetic information from more than 1 million American volunteers to learn how genetic variants affect health and disease. Rough Cut (no reporter narration). Video provided by Reuters
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins