Featured Research

from universities, journals, and other organizations

Cancer-cell quirk could be exploited to develop new drugs that starve tumors

Date:
September 17, 2010
Source:
Massachusetts Institute of Technology
Summary:
Scientists report a previously unknown element of cancer cells' peculiar metabolism. They found that cells can trigger an alternative biochemical pathway that speeds up their metabolism and diverts the byproducts to construct new cells.

In a paper appearing in the Sept. 16 online edition of Science, Matthew Vander Heiden assistant professor of biology and member of the David H. Koch Institute for Integrative Cancer Research at MIT and researchers at Harvard University report a previously unknown element of cancer cells' peculiar metabolism. They found that cells can trigger an alternative biochemical pathway that speeds up their metabolism and diverts the byproducts to construct new cells.

Related Articles


The finding could help scientists design drugs that block cancer-cell metabolism, essentially starving them of the materials they need to grow and spread. Vander Heiden has just begun tests in mice of several such drugs.

Just as trees can be turned into logs to build a new house, or firewood to generate heat, sugar can serve many purposes. In a normal cell, most of the sugar is burned up for energy, with little left over to build anything new. Cancer cells, on the other hand, need building blocks for new cells as well as energy.

"If you have a forest of trees, you can take all the trees and burn them and release a lot of energy, but you haven't built anything," says Vander Heiden. "To build a house out of it, you need to save some logs to turn them into lumber."

Most human cells burn a six-carbon sugar called glucose. Through a long chain of reactions that require oxygen, the cells extract energy from the sugar and store it in molecular energy packets known as ATP. Cells use ATP to power a variety of functions, such as transporting molecules in and out of the cell, contracting muscle fibers and maintaining cell structure.

Glucose metabolism normally occurs in two stages, the first of which is known as glycolysis. It has been known for decades that cancer cells perform gylcolysis only, skipping the second stage, which is where most of the ATP is generated.

Vander Heiden's new study focuses on glycolysis, traditionally thought to be a linear, nine-step process by which a cell turns one molecule of glucose into two molecules of pyruvate, an organic compound with three carbon atoms. That pyruvate is usually fed into the second phase of glucose metabolism.

"Everyone takes it for granted that this is how it works," says Vander Heiden, who did this research as a postdoctoral fellow in the lab of Harvard Medical School Professor Lewis Cantley, senior author of the paper. But the new study shows that "there is another way it can work, and this other way seems to be at play in proliferating cells." That could include rapidly dividing embryonic cells as well as cancer cells.

Scientists already knew that cancer cells replace one type of a key metabolic enzyme known as pyruvate kinase with another. Both versions of the enzyme (PKM1 and PKM2) catalyze the very last step of glycolysis, which is the transformation of a compound called PEP to the final product, pyruvate.

In the new study, the researchers found that PEP is involved in a previously unknown feedback loop that bypasses the final step of glycolysis. In cancer cells, PKM2 is not very active, causing PEP to accumulate. That excess PEP activates an enzyme called PGAM, which catalyzes an earlier step in glycolysis. When PGAM receives that extra boost, it produces even more PEP, creating a positive feedback loop in which the more PEP a cell has, the more it makes.

The most important result of this loop is that the cell generates a large pool of another chemical that is formed during an intermediate step of the reaction chain. Vander Heiden believes this compound, called 3-phosphoglycerate, is diverted into synthetic pathways such as the production of DNA, which can become part of a new cancer cell. In future studies, he plans to investigate how that diversion occurs.

This study suggests that drugs that activate PKM2 could be promising cancer treatments, says Vander Heiden. If PKM2 were highly activated, cancer cells would alter the metabolism of PEP, blocking the alternative pathway and hindering the production of new building blocks.

 Funding was provided by the Damon Runyon Cancer Research Foundation, the Burroughs Wellcome Fund, the American Cancer Society and the National Institutes of Health.


Story Source:

The above story is based on materials provided by Massachusetts Institute of Technology. Note: Materials may be edited for content and length.


Journal Reference:

  1. Matthew G. Vander Heiden, Jason W. Locasale, Kenneth D. Swanson, Hadar Sharfi, Greg J. Heffron, Daniel Amador-Noguez, Heather R. Christofk, Gerhard Wagner, Joshua D. Rabinowitz, John M. Asara, and Lewis C. Cantley. Evidence for An alternative glycolytic Pathway in rapidly proliferating cells. Science, 17 September 2010: 1492-1499 DOI: 10.1126/science.1188015

Cite This Page:

Massachusetts Institute of Technology. "Cancer-cell quirk could be exploited to develop new drugs that starve tumors." ScienceDaily. ScienceDaily, 17 September 2010. <www.sciencedaily.com/releases/2010/09/100916145055.htm>.
Massachusetts Institute of Technology. (2010, September 17). Cancer-cell quirk could be exploited to develop new drugs that starve tumors. ScienceDaily. Retrieved December 19, 2014 from www.sciencedaily.com/releases/2010/09/100916145055.htm
Massachusetts Institute of Technology. "Cancer-cell quirk could be exploited to develop new drugs that starve tumors." ScienceDaily. www.sciencedaily.com/releases/2010/09/100916145055.htm (accessed December 19, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Friday, December 19, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

The Best Tips to Curb Holiday Carbs

The Best Tips to Curb Holiday Carbs

Buzz60 (Dec. 19, 2014) — It's hard to resist those delicious but fattening carbs we all crave during the winter months, but there are some ways to stay satisfied without consuming the extra calories. Vanessa Freeman (@VanessaFreeTV) has the details. Video provided by Buzz60
Powered by NewsLook.com
Sierra Leone Bikers Spread the Message to Fight Ebola

Sierra Leone Bikers Spread the Message to Fight Ebola

AFP (Dec. 19, 2014) — More than 100 motorcyclists hit the road to spread awareness messages about Ebola. Nearly 7,000 people have now died from the virus, almost all of them in west Africa, according to the World Health Organization. Video provided by AFP
Powered by NewsLook.com
Researchers Test Colombian Village With High Alzheimer's Rates

Researchers Test Colombian Village With High Alzheimer's Rates

AFP (Dec. 19, 2014) — In Yarumal, a village in N. Colombia, Alzheimer's has ravaged a disproportionately large number of families. A genetic "curse" that may pave the way for research on how to treat the disease that claims a new victim every four seconds. Duration: 02:42 Video provided by AFP
Powered by NewsLook.com
Double-Amputee Becomes First To Move Two Prosthetic Arms With His Mind

Double-Amputee Becomes First To Move Two Prosthetic Arms With His Mind

Buzz60 (Dec. 19, 2014) — A double-amputee makes history by becoming the first person to wear and operate two prosthetic arms using only his mind. Jen Markham has the story. Video provided by Buzz60
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:

Strange & Offbeat Stories

 

Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins