Navigation Links
MIT researchers discover an unexpected twist in cancer metabolism
Date:9/16/2010

CAMBRIDGE, Mass. -- 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.

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.


'/>"/>

Contact: Jennifer Hirsch
jfhirsch@mit.edu
617-253-1682
Massachusetts Institute of Technology
Source:Eurekalert

Related medicine news :

1. OHSU researchers able to determine brain maturity through analyzing MRI scans
2. Lung cancer culprit could offer target for therapy, UT Southwestern researchers report
3. Researchers Develop Touch-Sensitive e-Skin
4. NYU researchers identify new neurological deficit behind lazy eye
5. SWOG names 5 cancer researchers outstanding Young Investigators
6. Adults demonstrate modified immune response after receiving massage, Cedars-Sinai researchers show
7. Researchers identify gene set that shows which patients benefit from chemo after surgery
8. Researchers will test suicide prevention program in high schools
9. Mount Sinai researchers find new target to improve pain management
10. Non-invasive therapy significantly improves depression, UCLA researchers say
11. For the first time, researchers identify and isolate adult mammary stem cells in mice
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:3/24/2017)... ... 2017 , ... Judy Buchanan, co-owner of Serenity Natural Health ... says, “I am passionate about sharing Reiki as a holistic, complementary therapy with ... time.” , A Certified Medical Reiki™ Master trained by Raven Keys Medical Reiki™ ...
(Date:3/24/2017)... ... ... “End Time GPS”: a dauntless and enlightened study of the second-coming of Christ, ... of published author, Wesley Gerboth, a World War II veteran, with a highly-regarded reputation ... age ninety-one, he shares the Wisdom God bestowed upon him in this publication. ...
(Date:3/24/2017)... ... March 24, 2017 , ... ... stories about real people of God in congregations across the United States. ... Presbyterian minister ordained in 1964 who has served congregations in seven states throughout ...
(Date:3/23/2017)... Greensboro, NC & Seattle, WA (PRWEB) , ... March 23, 2017 ... ... international public health emergency and now estimates that there could be four million Zika-related ... fastest growing epidemics to date with numbers of US cases reported per year skyrocketing ...
(Date:3/23/2017)... ... March 23, 2017 , ... The physicians of KSF ... the greater Houston Area. The new location is located at 2255 E. Mossy Oaks ... Springwoods Village. This newest location will provide patients living in the north Houston area ...
Breaking Medicine News(10 mins):
(Date:3/24/2017)... Research and Markets has announced the addition of the ... 2022" report to their offering. ... The global wound care market was worth $24,482.9 million in ... during 2016-2022 Among the various wound care products type, the ... market in 2015. Among the various applications, surgical wound segment held the ...
(Date:3/24/2017)... Research and Markets has announced the addition of the "Dental ... ... markets for Dental Implants in US$ Million. The report provides separate comprehensive ... , Europe , Asia-Pacific , ... Annual estimates and forecasts are provided for the period 2015 through ...
(Date:3/24/2017)... 24, 2017 ShangPharma, a leading ... cost-effective drug development and discovery services, technology, ... industry, announced today the intent for a ... be consolidating the Contract Research Organizations (CRO) ... ChemPartner. These entities include ChemPartner Shanghai, ChemPartner ...
Breaking Medicine Technology: