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

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 2,800+ scientific posters on ePosters
  • More than 4,000+ 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

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
Scientific News
Exploring the Causes of Cancer
Queen's research to understand the regulation of a cell surface protein involved in cancer.
Measuring microRNAs in Blood to Speed Cancer Detection
A simple, ultrasensitive microRNA sensor holds promise for the design of new diagnostic strategies and, potentially, for the prognosis and treatment of pancreatic and other cancers.
Novel Proteins Linked to Huntington's Disease
University of Florida Health researchers have made a new discovery about Huntington's disease, showing that the gene that causes the fatal disorder makes an unexpected "cocktail" of mutant proteins that accumulate in the brain.
Enzyme Critical to Maintaining Telomere Length Discovered
New method expected to speed understanding of short telomere diseases and cancer.
New Method Identifies Up to Twice as Many Proteins and Peptides
An international team of researchers developed a method that identifies up to twice as many proteins and peptides in mass spectrometry data than conventional approaches.
Metabolic Profiles Distinguish Early Stage Ovarian Cancer with Unprecedented Accuracy
Studying blood serum compounds of different molecular weights has led scientists to a set of biomarkers that may enable development of a highly accurate screening test for early-stage ovarian cancer.
New Way to Force Stem Cells to Become Bone Cells
Potential therapies based on this discovery could help people heal bone injuries or set hardware, such as replacement knees and hips.
Long-Sought Protein Sensor for the ‘Sixth Sense’ Discovered
In a study led by scientists from The Scripps Research Institute (TSRI)the sensor protein for propioception has been identified.
How Viruses Commandeer Human Proteins
Researchers have produced the first image of an important human protein as it binds with ribonucleic acid (RNA), a discovery that could offer clues to how some viruses, including HIV, control expression of their genetic material.
Tracking How Herpes Simplex Virus Moves Through Cells
In a recent study, Derek Walsh, PhD, associate professor of Microbiology-Immunology, and his team showed how the herpes simplex virus (HSV) exploits microtubule plus-end tracking proteins to initiate transport and infection in human cells.
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
2,800+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,000+ scientific videos