Corporate Banner
Satellite Banner
Technology
Networks
Scientific Communities
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Protein Controlling Glucose Metabolism also a Tumor Suppressor

Published: Tuesday, December 11, 2012
Last Updated: Tuesday, December 11, 2012
Bookmark and Share
A protein known to regulate how cells process glucose also appears to be a tumor suppressor, adding to the potential that therapies directed at cellular metabolism may help suppress tumor growth.

In their report in the Dec. 7 issue of Cell, a multi-institutional research team describes finding that cells lacking the enzyme SIRT6, which controls how cells process glucose, quickly become cancerous. They also found evidence that uncontrolled glycolysis, a stage in normal glucose metabolism, may drive tumor formation in the absence of SIRT6 and that suppressing glycolysis can halt tumor formation.

"Our study provides solid evidence that SIRT6 may function as a tumor suppressor by regulating glycolytic metabolism in cancer cells," says Raul Mostoslavsky, MD, PhD, of the Massachusetts General Hospital (MGH) Cancer Center, senior author of the report. "Critically, our findings indicate that, in tumors driven by low SIRT6 levels, drugs that may inhibit glycolysis - currently a hot research topic among biotechnology companies - could have therapeutic benefits."

The hypothesis that a switch in the way cells process glucose could set off tumor formation was first proposed in the 1920s by German researcher Otto Warburg, who later received the Nobel Prize for discoveries in cellular respiration. He observed that, while glucose metabolism is normally a two-step process involving glycolysis in the cellular cytoplasm followed by cellular respiration in the mitochondria, in cancer cells rates of glycolysis are up to 200 times higher. Warburg's proposition that this switch in glucose processing was a primary cause of cancer did not hold up, as subsequent research supported the role of mutations in oncogenes, which can spur tumor growth if overexpressed, and tumor suppressors, which keep cell proliferation under control. But recent studies have suggested that alterations in cellular metabolism may be part of the process through which activated oncogenes or inactivated tumor suppressors stimulate cancer formation.

A 2010 study led by Mostoslavsky found that the absence of SIRT6 - one of a family of proteins called sirtuins that regulate many important biological pathways - appears to "flip the switch" from normal glucose processing to the excess rates of glycolysis seen in cancer cells. The current study was specifically designed to investigate whether SIRT6's control of glucose metabolism also suppresses tumor formation. The research team first showed that cultured skin cells from embryonic mice lacking SIRT6 proliferated rapidly and quickly formed tumors when injected into adult mice. They also confirmed elevated glycolysis levels in both cells lacking SIRT6 and tumor cells and found that formation of tumors through SIRT6 deficiency did not appear to involve oncogene activation.

Analysis of tumor samples from patients found reduced SIRT6 expression in many - particularly in colorectal and pancreatic tumors. Even among patients whose tumors appeared to be more aggressive, higher levels of SIRT6 expression may have delayed or, for some, prevented relapse. In a mouse model programmed to develop numerous colon polyps, the researchers showed that lack of intestinal SIRT6 expression tripled the formation of polyps, many of which became invasive tumors. Treating the animals with a glycolytic inhibitor significantly reduced tumor formation, even in the absence of SIRT6.

"Our results indicate that, at least in certain cancers, inhibiting glycolytic metabolism could provide a strong alternative way to halt cancer growth, possibly acting synergistically with current anti-tumor therapies," says Mostoslavsky, an assistant professor of Medicine at Harvard Medical School. "Cancer metabolism has only recently emerged as a hallmark of tumorigenesis, and the field is rapidly expanding. With the current pace of research and the speed at which some basic discoveries are moving into translational studies, it is likely that drugs targeting cancer metabolism may be available to patients in the near future."


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 2,400+ scientific posters on ePosters
  • More Than 3,700+ 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

Evo-Engineered CRISPR-Cas9s Hit More Gene-Editing Targets
Scientists have engineered a more effective CRISPR- Cas9 system paving the way for more advanced applications.
Wednesday, June 24, 2015
Reducing Chemotherapy Drug’s Cardiac Side Effects
Preventing doxorubicin-induced cardiotoxicity could improve chemotherapy outcomes, reduce heart failure risk.
Thursday, December 11, 2014
Direct Drug Screening Of Biopsies Could Overcome Resistance
Combining genetic with pharmacologic screening of tumors may enable truly individualized treatment regimens.
Monday, November 17, 2014
Culture System Replicates Course Of Alzheimer’s Disease
Three-dimensional system should significantly reduce time and costs of drug development.
Monday, October 20, 2014
Genetic Signals Reflect the Evolutionary Impact of Cholera
Study identifies regions of genome associated with cholera susceptibility in Bangladesh.
Monday, July 08, 2013
Powerful Gene-Editing Tool Appears to Cause Off-Target Mutations in Human Cells
Results indicate need to improve precision of CRISPR-Cas RNA-guided nucleases.
Wednesday, June 26, 2013
Mass. General, Duke Study Identifies Two Genes that Combine to Cause Rare Syndrome
Mutations in genes that regulate cellular metabolism found in families with ataxia, dementia and reproductive failure.
Monday, May 13, 2013
Phase 1 ALS Trial is First to Test Antisense Treatment of Neurodegenerative Disease
No serious adverse effects seem from central-nervous-system infusion of drug that blocks mutated protein.
Tuesday, April 09, 2013
Detection, Analysis of 'Cell Dust' may Allow Diagnosis, Monitoring of Brain Cancer
System combining nanotechnology and NMR detects particles shed by brain tumors in bloodstream.
Thursday, November 15, 2012
Circulating Tumor Cells can Reveal Genetic Signature of Dangerous Lung Cancers
MGH-developed device promises improvements in targeted therapy, treatment monitoring.
Friday, July 04, 2008
Gene Variation may Elevate Risk of Liver Tumor in Patients with Cirrhosis
A single alteration in the epidermal growth factor (EFG) gene may greatly increase the risk of developing hepatocellular carcinoma, researchers say.
Tuesday, January 08, 2008
Scientific News
RNAi Screening Trends
Understand current trends and learn which application areas are expected to gain in popularity over the next few years.
New Weapon in the Fight Against Blood Cancer
This strategy, which uses patients’ own immune cells, genetically engineered to target tumors, has shown significant success against multiple myeloma, a cancer of the plasma cells that is largely incurable.
TOPLESS Plants Provide Clues to Human Molecular Interactions
Scientists at Van Andel Research Institute have revealed an important molecular mechanism in plants that has significant similarities to certain signaling mechanisms in humans, which are closely linked to early embryonic development and to diseases such as cancer.
Toxin from Salmonid Fish has Potential to Treat Cancer
Researchers from the University of Freiburg decode molecular mechanism of fish pathogen.
Study Finds Non-Genetic Cancer Mechanism
Cancer can be caused solely by protein imbalances within cells, a study of ovarian cancer has found.
Scientists Create CRISPR/Cas9 Knock-In Mutations in Human T Cells
In a project spearheaded by investigators at UC San Francisco, scientists have devised a new strategy to precisely modify human T cells using the genome-editing system known as CRISPR/Cas9.
Researchers Find U.S. Breast Milk is Glyphosate Free
Washington State University scientists have found that glyphosate, the main ingredient in the herbicide Roundup, does not accumulate in mother’s breast milk.
Peering into the Vapors
Research suggests that e-cigarettes are much less harmful than previous studies have indicated.
New Technique for Mining Health-conferring Soy Compounds
A new procedure devised by U.S. Department of Agriculture (USDA) scientists to extract lunasin from soybean seeds could expedite further studies of this peptide for its cancer-fighting potential and other health benefits.
Long-sought Discovery Fills in Missing Details of Cell 'Switchboard'
A biomedical breakthrough reveals never-before-seen details of the human body’s cellular switchboard that regulates sensory and hormonal responses.
Scroll Up
Scroll Down
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
2,400+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
3,700+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FREE!