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

Probing What Fuels Cancer

Published: Monday, August 06, 2012
Last Updated: Monday, August 06, 2012
Bookmark and Share
Cancer is often described as a genetic disease, after all the transition a cell goes through in becoming cancerous tends to be driven by changes to the cell's DNA.

But genes, though hugely important, might not be the whole story. Researchers at Oxford University are interested in understanding how changes in cells' metabolism – the chemical processes through which cells get the energy they need – could also prime them to become cancerous.

They have just started collaborating with a lab at Keio University in Japan to bring large-scale techniques to the study of metabolic processes going on in cancer cells, much as gene technologies have given such insight into DNA changes involved in cancers.

'Altered cellular metabolism is a hallmark of cancer,' says Dr Patrick Pollard, who is leading this effort in the Nuffield Department of Clinical Medicine at Oxford.

This is not a new finding - it is something that has been known for a long time. The biochemist and Nobel laureate Otto Warburg pointed it out in the early 1900s. He observed that most cancer cells get the energy they need predominantly through a high rate of glycolysis (the metabolic process that breaks down glucose to release energy). It helps the cancer cells deal with the low oxygen levels that tend to be present in a tumour.

But whether dysfunctional metabolism causes cancer, as Warburg believed, or is something that happens afterwards is a different question.

In the meantime, gene studies rapidly progressed and gave us a picture of how genetic changes lead to cancer.

It goes something like this: DNA mutations spring up all the time in the body's cells, but most are quickly repaired. Alternatively the cell might shut down or be killed off before any damage is caused. However, the repair machinery is not perfect. If changes occur that bypass parts of the repair machinery or sabotage it, the cell can escape the body's normal controls on growth and further DNA changes can begin to accumulate as the cell switches to become cancerous.

So what has metabolism got to do with this? We get the energy we need from food of course, and we talk about our metabolism in the way our bodies make use of that food as a fuel for everything we do during the day. Our cells are the same. They have whole series of chemical reactions going on simultaneously to keep them working, wherever and whatever they are doing in the body – from heart cells to neurons in the brain and liver or pancreatic cells. Cellular metabolism is a constant process with thousands of metabolic reactions happening at the same time, all of which need to be regulated to keep our cells ticking over healthily.

It's what happens when the regulation of cellular metabolic processes goes wrong that could be of interest. And it's only a lot more recently that techniques to probe the entirety of metabolic processes in the cell have advanced. The result is something of a return to vogue for studies to understand how altered cellular metabolism and cancer are linked.

Studies of the genetic basis of cancer and dysfunctional metabolism in cancer cells are complementary, Patrick believes. 'Genomic data is very important, but certain changes in cells can’t always be accounted for by genetics.'

He is now collaborating with Professor Tomoyoshi Soga's large lab at Keio University in Japan, which has been at the forefront of developing the technology for metabolomics research over the past couple of decades (metabolomics being the ugly-sounding term used to describe research that studies all metabolic processes at once, like genomics is the study of the entire genome).

The Japanese lab's ability to screen samples for thousands of compounds and metabolites at once, coupled with the access to tumour material and cell and animal models of disease in Oxford, should give great power to probe the metabolic changes that occur in cancer.

There is reason to believe that dysfunctional cell metabolism is important in cancer. Some genes with metabolic functions are associated with some cancers, and changes in the function of a metabolic enzyme have been implicated in the development of gliomas.

These results have led to the idea that some metabolic compounds, or metabolites, when they accumulate in cells, can cause changes to metabolic processes and set cells off on a path towards cancer.

Patrick Pollard and colleagues have now published a perspective article in the journal Frontiers in Molecular and Cellular Oncology that proposes fumarate as such an 'oncometabolite'. Fumarate is a standard compound involved in cellular metabolism.

In that article, the researchers summarise evidence (often from their own lab) that shows how accumulation of fumarate when an enzyme goes wrong affects various biological pathways in the cell. It shifts the balance of metabolic processes and disrupts the cell in ways that could favour development of cancer.

This work on metabolic pathways involving fumarate has already led to a cheap and reliable diagnostic test for a rare form of cancer caused by accumulation of fumarate within cells. Their test for hereditary leiomyomatosis and renal cell cancer (HLRCC) involves screening tumour samples for a particular molecular fingerprint unique to this type of cancer. The Oxford researchers are now hoping to develop their test for clinical use, largely to help with genetic counselling for families as the condition can be inherited.

While HLRCC is a rare type of cancer, Patrick Pollard says: 'Metabolic changes are observed in most cancers, so there could be wider implications. Lots of findings about pathways that are important in cancer come from studying rare cancers.'

This is where the collaboration with Keio University comes in. The Keio group is able to label glucose or glutamine, basic biological sources of fuel for cells, and track the pathways cells use to burn up the fuel. It allows the scientists to work out the metabolic pathways that are being used preferentially by different cell types including cancer-derived cell lines.

Patrick gives an example of how the research might progress: they could profile the metabolites in a cohort of tumour samples and matched normal tissue. This would produce a dataset of the concentrations of hundreds of different metabolites in each group. Statistical approaches could suggest which metabolic pathways were abnormal. These would then be the subject of experiments targeting the pathways to confirm the relationship between changed metabolism and uncontrolled growth of the cancer cells.

Patrick and colleagues write in their latest article that the shift in focus of cancer research to include cancer cell metabolism 'has highlighted how woefully ignorant we are about the complexities and interrelationships of cellular metabolic pathways'.

Hopefully, research efforts like this large-scale approach to understanding cell metabolism can give insight into how cells respond to shifted metabolic processes and how this is associated with the development of some cancers.


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 2,500+ 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

Gene Links Offer Picture of Biology Underlying Diabetes
Findings are published in the journal Nature Genetics.
Tuesday, August 14, 2012
Scientific News
Liquid Biopsies: Utilization of Circulating Biomarkers for Minimally Invasive Diagnostics Development
Market Trends in Biofluid-based Liquid Biopsies: Deploying Circulating Biomarkers in the Clinic. Enal Razvi, Ph.D., Managing Director, Select Biosciences, Inc.
Self-Assembling, Biomimetic Membranes May Aid Water Filtration
A synthetic membrane that self assembles and is easily produced may lead to better gas separation, water purification, drug delivery and DNA recognition, according to an international team of researchers.
Researchers Discover Immune System’s 'Trojan Horse'
Oxford University researchers have found that human cells use viruses as Trojan horses, transporting a messenger that encourages the immune system to fight the very virus that carries it.
How Cholesterol Leads to Clogged Arteries
A new study shows that when immune cells called neutrophils are exposed to cholesterol crystals, they release large extracellular web-like structures that trigger the production of inflammatory molecules linked to artherosclerosis.
Study Questions Presence in Blood of Heart-Healthy Molecules from Fish Oil Supplements
A new study from the Perelman School of Medicine at the University of Pennsylvania questions the relevance of fish oil-derived SPMs and their purported anti-inflammatory effects in humans.
Identifying a Key Growth Factor in Cell Proliferation
Researchers discover that aspartate is a limiter of cell proliferation.
Toxin from Salmonid Fish has Potential to Treat Cancer
Researchers from the University of Freiburg decode molecular mechanism of fish pathogen.
Key Player in Diabetic Kidney Disease Revealed
Discovery could lead to new and better diagnostic marker for chronic kidney disease.
Can Cell Cycle Protein Prevent or Kill Breast Cancer Tumors?
An MD Anderson study has shown the potential of a simple molecule involved in cancer metabolism as a powerful therapeutic.
Study Reveals Improved Way to Interpret High-Throughput Biological Data
A recent study has revealed a novel workflow, identifying associations between molecules to provide insights into cellular metabolism and gene expression in complex biological systems.
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
2,500+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
3,700+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FREE!