Corporate Banner
Satellite Banner
Metabolomics & Lipidomics
Scientific Community
Become a Member | Sign in
Home>News>This Article

Gene Mutation Gives Boost to Brain Cancer Cells

Published: Monday, June 10, 2013
Last Updated: Monday, June 10, 2013
Bookmark and Share
An international team of researchers has found that a singular gene mutation helps brain cancer cells to not just survive, but grow tumors rapidly.

The findings are published online in the journal Cell Metabolism.

Mischel, who heads the Ludwig Institute's molecular pathology laboratory based at UC San Diego, and colleagues focused upon a process called alternative splicing, in which a single gene encodes for multiple proteins by including or excluding different, specific regions of DNA.

Alternative splicing is a tightly regulated and normal activity in healthy cells. For Mischel and colleagues in Los Angeles, Ohio and Japan, the question was whether mutations of a gene called EGFRvIII caused differential alternative splicing in glioblastoma multiformes (GBMs), the most common and aggressive type of malignant brain tumor. Median survival after GBM diagnosis is just 15 months with standard-of care radiation and chemotherapy. Without treatment, it is less than five months.

The scientists were particularly interested in whether the EGFRvIII mutation induced alternative splicing events that resulted in deregulation of normal cellular metabolism. "We focused on the ‘Warburg Effect,' a common metabolic derangement in cancer that enables tumor cells to metabolize glucose in a way that provides both a sufficient supply of energy and a source of building blocks that can be used for growth," Mischel said.

They discovered a complex but compelling series of consequential events: The EGFRvIII mutation controls expression of a splicing factor called HNRNPA1, which initiates an alternatively spliced form of a regulatory protein called Max. The alternative form is called Delta Max.

Max is associated with MYC, a gene that drives tumor growth and the Warburg Effect in cancer. "Unlike the regular form of Max," said Mischel, "Delta Max actually enhances c-MYC activity, specifically by promoting the glycolytic phenotype of the tumor cells." In other words, the EGFRvIII mutation and subsequent alternative splicing commandeer the cell's metabolic machinery in a way that lets it take up and use glucose to promote rapid tumor growth.

Mischel noted that the findings are specific to the EGFRvIII mutation and GBMs. It's not known whether other oncogenes are able to exploit alternative splicing in similar fashion.

The findings, according to Mischel, provide two clear insights. First, they highlight the central role of EGFRvIII in GBM pathogenesis and its critical role in altering cellular metabolism in tumors. Second, they show that oncogenes can regulate cell metabolism through alternative splicing, which may provide a new set of targets for oncogene-specific drug development.

Further Information
Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,600+ scientific posters on ePosters
  • More than 3,800+ scientific videos on LabTube
  • 35 community eNewsletters

Sign In

Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Disabling Enzyme Cripples Tumors, Cancer Cells
Knocking out a single enzyme dramatically cripples the ability of aggressive cancer cells to spread and grow tumors.
Thursday, September 05, 2013
Key Protein is Linked to Circadian Clocks, Helps Regulate Metabolism
Study sheds light on molecular basis for metabolic health and disease.
Wednesday, June 19, 2013
Researchers Engineer Metabolic Pathway in Mice to Prevent Diet-Induced Obesity
Researchers have constructed a non-native pathway in mice that increased fatty acid metabolism and resulted in resistance to diet-induced obesity.
Tuesday, June 09, 2009
Snails and Humans Use Same Genes to Tell Right from Left
Biologists have tracked down genes that control the handedness of snail shells, and they turn out to be similar to the genes used by humans to set up the left and right sides of the body.
Monday, December 29, 2008
Scientific News
Newly Identified Biochemical Pathway Could Be Target for Insulin Control
Researchers at Duke Medicine and the University of Alberta are reporting the identification of a new biochemical pathway to control insulin secretion from islet beta cells in the pancreas, establishing a potential target for insulin control.
Dirty,Crusty Meals Fit for (Long-Dormant) Microbes
Researchers apply the latest analytical techniques to further our understanding of desert biocrusts.
CSI -- On The Metabolite's Trail
Bioinformaticians at the University of Jena make the most efficient search engine for molecular structures available online.
Developing a Breathalyzer-Type Low Blood Sugar Warning Device For Diabetes
A multidisciplinary team of researchers at Indiana University-Purdue University Indianapolis has been awarded a $738,000 National Science Foundation grant to develop a breathalyzer-type device to detect the onset of hypoglycemia, or low blood sugar episodes, in people with diabetes.
Identifying The 'Dimmer Switch' Of Diabetes
University of Alberta research gives new insight into what causes Type 2 diabetes.
10 to 1: Bugs Win in NASA study
Bugs are winning out, and that's a good thing according to NASA's Human Research Program.
MYC Oncogene Disrupts Cancers Rhythm
Findings inform time-dependent treatment for reducing side effects and increasing effectiveness of cancer medications.
Keeping Gut Bacteria in Balance Could Help Delay Age-related Diseases
A new study suggests that analyzing intestinal bacteria could be a promising way to predict health outcomes as we age.
Genome Mining Effort Discovers 19 New Natural Products in Four Years
Each of these products is a potential new drug. One of them has already been identified as an antibiotic.
New CRISPR-Cas9 Strategy Edits Genes Two Ways
A team of Harvard and MIT researchers have developed a way to perform genome engineering and gene regulation at the same time.
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,600+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
3,800+ scientific videos