Navigation Links
Understanding cancer energetics

It's long been known that cancer cells eat a lot of sugar to stay alive. In fact, where normal, noncancerous cells generate energy from using some sugar and a lot of oxygen, cancerous cells use virtually no oxygen and a lot of sugar. Many genes have been implicated in this process and now, reporting in the May 27 issue of Cell, researchers at the Johns Hopkins University School of Medicine have discovered that this so-called Warburg effect is controlled.

"It turns out to be a feed-forward mechanism, where protein A turns on B, which in turn goes back and helps A do more," says Gregg Semenza, M.D., Ph.D., the C. Michael Armstrong Professor of Medicine, director of the vascular program in Hopkins' Institute for Cell Engineering and a member of the McKusick-Nathans Institute of Genetic Medicine. "PKM2 normally functions as an enzyme involved in the metabolism of glucose, but in this case we have demonstrated a novel role in the control of gene expression in cancer cells."

Nearly 20 years ago, Semenza's research team discovered that HIF-1 can turn on a number of genes that that help cells survive when oxygen levels fall too low. In addition to genes that contribute to building new blood vessels, HIF-1 also turns on genes involved in the metabolic process that turns glucose into energy. One of those genes, pyruvate kinase M2 or PKM2, catalyzes the first step of this metabolic process and is present only in cancer cells.

To figure out whether and if HIF-1 and PKM2 interact, the team first engineered cells to have or lack HIF-1. They kept them in high or low oxygen for 24 hours and found that cells starved of oxygen, but containing HIF-1, had more PKM2 than cells without HIF-1, suggesting that HIF-1 controls the production of PKM2.

The team then asked if HIF-1 and PKM2 physically interact with each other by isolating one of the two proteins from cells; they found that pulling one out also resulted in the other coming along for the ride, showing that the two proteins do in fact bind to each other.

Knowing that the primary function of HIF-1 is to bind DNA and turn on specific genes, Semenza's team next asked whether PKM2 somehow helped HIF-1 do that. They examined genes known to be activated by HIF-1 in low oxygen after the removal of PKM2 and found that without PKM2, less HIF-1 was bound to DNA.

Now armed with evidence that PKM2 helps HIF-1 turn on genes, the team looked at the activity of genes directly involved in the metabolic pathway that burns so much sugar in cancer cells and compared genes known to be activated by HIF-1 with those not affected by HIF-1. Removing PKM2 from cells had no effect on genes not controlled by HIF-1 but reduced the activity of HIF-1-controlled genes.

"These results were really astounding," says Semenza. "In addition to solving the long-standing mystery of the Warburg effect, we also discovered that PKM2 may play a far broader role in promoting cancer progression than has been appreciated before."


Contact: Audrey Huang
Johns Hopkins Medical Institutions

Related medicine news :

1. Exploring the limits: Understanding the challenges facing Winter Olympic champions
2. MRC scientists announce advance in understanding bodys natural defenses
3. Health Occupations Students of America, Inc. and the U.S. Army Sign Memorandum of Understanding in Support of Improving Career Options for Nations Students
4. Understanding causes of cancer and chronic disease: The Canadian Partnership for Tomorrow Project
5. Study Makes Strides in Understanding Ovarian Cancer
6. Researchers make advances in understanding causes, treatments and outcomes of liver disease
7. Existence Genetics is Pioneering the Field of Predictive Medicine - Nexus Technologies Critical in Understanding and Preventing Deadly Disease
8. Understanding the relationship between bacteria and obesity
9. Rochester advances understanding of deadly form of malaria
10. Understanding Back Pain May Improve Management, Study Suggests
11. FSU study takes novel approach to understanding pituitary function
Post Your Comments:
(Date:10/13/2017)... ... October 13, 2017 , ... PurhealthRX , a leading ... Purzorb™ technology. Applying the Purzorb™process to full spectrum CBD oil will revolutionize the rapidly ... CBD form that can be easily incorporated into liquid products, while reducing costs to ...
(Date:10/13/2017)... ... October 13, 2017 , ... Many families have long-term insurance that ... insurance companies have a waiver for care if the client has a cognitive impairment ... family pays for care, is often waived, so the benefits from their insurance start ...
(Date:10/13/2017)... Texas (PRWEB) , ... October 13, 2017 , ... Yisrayl ... this week that explains one of the most popular and least understood books in ... like cryptic and puzzling descriptions that have baffled scholars for centuries. Many have tossed ...
(Date:10/13/2017)... ... , ... “America On The Brink”: the Christian history of the United States ... creation of published author, William Nowers. Captain Nowers and his wife, Millie, have ... thirty years in the Navy. Following his career as a naval aviator and ...
(Date:10/12/2017)... , ... October 12, 2017 , ... ... to meet the demand of today’s consumer and regulatory authorities worldwide. From Children’s ... experts and tested to meet the highest standard. , These products are ...
Breaking Medicine News(10 mins):
(Date:10/11/2017)... Texas , Oct. 11, 2017  True ... services, has amplified its effort during National Breast ... about hereditary cancer risks. ... of Clinical Oncology calculated that more than 10 ... have inherited mutations in BRCA1 or BRCA2 and have ...
(Date:10/10/2017)... 10, 2017  NDS received FDA 510(k) clearance in May 2017 ... display stand specifically designed for endoscopy environments. An innovative secondary monitor ... clinical solution to support the improvement of patient outcomes, procedural efficiency, ... ... ...
(Date:10/7/2017)... IRVING, Texas , Oct. 6, 2017   ... industry with more than $100 billion in purchasing power, ... industry news and information. The Newsroom is ... chain and industry trends, infographics, expert bios, news releases, ... Besides having access to a wealth of resources at ...
Breaking Medicine Technology: