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

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

Join For Free

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 3,000+ scientific posters on ePosters
  • More than 4,500+ 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 TechnologyNetworks.com 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
New Treatment for Pancreatic Cancer
Researchers at Purdue University have shown how controlling cholesterol metabolism in pancreatic cancer cells reduces metastasis.
Plasma Biomarkers for Breast Cancer Diagnosis
Plasma lipidomics profiling identified lipid biomarkers in distinguishing early-stage breast cancer from benign lesions.
How Different People Respond To Aspirin
Study findings could be used to help identify those who would benefit most from aspirin use.
Altered Metabolism of Four Compounds Drives Glioblastoma Growth
Findings suggest new ways to treat the malignancy, slow its progression and reveal its extent more precisely.
A Metabolic Twist that Drives Cancer Survival
A novel metabolic pathway that helps cancer cells thrive in conditions that are lethal to normal cells has been identified.
Liver-On-Chip Tracks Dynamics of Cellular Function
Hebrew University’s liver-on-chip platform is uniquely able to monitor metabolic changes indicating mitochondrial damage occurring at drug concentrations previously regarded as safe.
Living Off the Fat of the Land
Do cancer cells synthesize the parts for new cells or scavenge them from the environment?
Liver Disease, Obesity Linked
Kanazawa University researchers find similarities in the impeded signalling between central insulin activity and glucose production in the liver for both obese mice and mice that have had the vagus nerve removed.
Decoding Ties Between Vascular Disease, Alzheimer’s
NIH consortium uses big data, team science to uncover complex interplay of factors.
Gene Identified that May Worsen Cancer Outcome
Some patients with breast cancer, lung cancer and leukaemia seem to fare poorly after treatment because of the effects of a particular gene, a new study finds.
SELECTBIO

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
3,000+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,500+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!