Blocking key enzyme in cancer cells could lead to new therapy
Researchers hope to exploit cancer's unique metabolic profile
2013-08-02
(Press-News.org) Researchers from the University of Illinois at Chicago College of Medicine have identified a characteristic unique to cancer cells in an animal model of cancer -- and they believe it could be exploited as a target to develop new treatment strategies.
An enzyme that metabolizes the glucose needed for tumor growth is found in high concentrations in cancer cells, but in very few normal adult tissues. Deleting the gene for the enzyme stopped the growth of cancer in laboratory mice, with no associated adverse effects, reports Nissim Hay, UIC professor of biochemistry and molecular genetics, and his colleagues in the August 12 issue of Cancer Cell.
Targeting glucose metabolism for cancer therapy -- while avoiding adverse effects in other parts of the body -- has been a "questionable" strategy, Hay said. But he and his coworkers showed that the glucose-metabolism enzyme hexokinase-2 can be almost completely eliminated in adult mice without affecting normal metabolic functions or lifespan.
Hexokinase-2 is abundant in embryos but absent in most adult cells, where related enzymes take over its role in metabolism. One of the changes that mark a cell as cancerous is expression of the embryonic enzyme. Hay and his colleagues showed that the embryonic version is required for cancer cells to proliferate and grow, and that eliminating it halts tumor growth.
They developed a mouse strain in which they could silence or delete the HK2 gene in the adult animal, and they found that these mice could not develop or sustain lung or breast cancer tumors but were otherwise normal and healthy.
"We have deleted the HK2 gene systemically in these mice, and they have been living for more than two years now. Their lifespan is the same as normal mice," Hay said.
The researchers also looked at human lung and breast cancer cells in the lab, and found that if they eliminated all HK2, the cells stopped growing.
"We think that the process we used to delete the HK2 gene is not absolutely perfect, so there must be some low levels of HK2 in the mice. But that seems to be enough for the cells that use HK2, and the therapeutic effects on tumors in these mice are stable."
Hay thinks the enzyme is involved in making the building-blocks for the DNA of cancer cells, which need lots of all cellular components as they rapidly divide.
"Without HK2, the cancer cells don't make enough DNA for new cells, and so tumor growth comes to a standstill," said Hay.
INFORMATION:
Krushna C. Patra, Qi Wang, Prashanth Bhaskar, Luke Miller, Zebin Wang from UIC; Will Wheaton, Navdeep Chandel from Northwestern University Feinberg School of Medicine; Markku Laasko from the University of Eastern Finland, William Muller from McGill University in Montreal; Eric Allen, Abhishek Jha, Gromoslaw Smolen, Michelle Clasquin from Agios Pharmaceuticals; and Brooks Robey from Dartmouth Medical School also contributed to this research.
The research was supported by VA Merit Award BX000733, by NIH grants AG016927 and CA090764, and in part by the UIC Center for Clinical and Translational Sciences Award Number ULRR029879, and grant from the Chicago Biomedical Consortium with support from The Searle Funds at The Chicago Community Trust to Hay. Patra was supported by Defense Department predoctoral fellowship W81XWH-11-1-0006.
END
ELSE PRESS RELEASES FROM THIS DATE:
2013-08-02
Las Cumbres Observatory Global Telescope (LCOGT), with first lights at nine new 1-meter telescopes since April of 2012, achieved another critical milestone by capturing the first on-sky image with a production Sinistro camera. In development for over six years, the camera is arguably more important than the telescopes that will use them. "A telescope is really nothing more than a large camera lens," explained Joe Tufts, instrumentation scientist on the Sinistro project. "A large, precise, stable, and very expensive camera lens."
Sinistro is the primary science camera ...
2013-08-02
NEW YORK (August 1, 2013) -- Researchers have discovered how an experimental drug is capable of completely eradicating human lymphoma in mice after just five doses. The study, led by researchers at Weill Cornell Medical College, sets the stage for testing the drug in clinical trials of diffuse large B-cell lymphoma (DLBCL), the most common subtype of non-Hodgkin lymphoma, itself the seventh most frequently diagnosed cancer in the U.S.
In the journal Cell Reports, published today online, the scientists describe how the powerful master regulatory transcription factor Bcl6 ...
2013-08-02
A boost in the speed of brain scans is unveiling new insights into how brain regions work with each other in cooperative groups called networks.
Scientists at Washington University School of Medicine in St. Louis and the Institute of Technology and Advanced Biomedical Imaging at the University of Chieti, Italy, used the quicker scans to track brain activity in volunteers at rest and while they watched a movie.
"Brain activity occurs in waves that repeat as slowly as once every 10 seconds or as rapidly as once every 50 milliseconds," said senior researcher Maurizio Corbetta, ...
2013-08-02
EAST LANSING, Mich. — If two women have the same genetic mutation that puts them at higher-than-average risk for a disease such as breast cancer, why does only one develop the disease?
In the current issue of PLOS Genetics, Michigan State University genetic scientists have begun to understand how the rest of the genome interacts with such mutations to cause the differences we see among individuals.
"It's been known for a while that genetic mutations can modify each other's effects," said Ian Dworkin, MSU associate professor of zoology and co-author of the paper. "And ...
2013-08-02
A trace substance in caramelized sugar, when purified and given in appropriate doses, improves muscle regeneration in a mouse model of Duchenne muscular dystrophy. The findings are published today, Aug. 1, in the journal Skeletal Muscle.
Morayma Reyes, professor of pathology and laboratory medicine, and Hannele Ruohola-Baker, professor of biochemistry and associate director of the Institute for Stem Cell and Regenerative Medicine, headed the University of Washington team that made the discovery. The first authors of the paper were Nicholas Ieronimakis,UW Department of ...
2013-08-01
In women who use donor eggs to become pregnant through in vitro fertilization (IVF), those who are obese are just as likely to become pregnant as normal weight women, according to a new report.
Studies have shown that obesity is associated with lower chances of pregnancy using IVF, but most of this work is limited to women using their own eggs. Research on outcomes for obese women using donor eggs has had mixed results.
The new analysis by investigators at Washington University School of Medicine in St. Louis and the University of California-Los Angeles pooled and analyzed ...
2013-08-01
Irvine, Calif., July 31, 2013 — Breath analysis may prove to be an accurate, noninvasive way to quickly determine the severity of bacterial and other infections, according to a UC Irvine study appearing online today in the open-access journal PLOS ONE.
Employing a chemical analysis method developed for air pollution testing, UC Irvine microbiologists and chemists were able to correlate inflammation levels in laboratory mice to the amount of naturally produced carbon monoxide and other gases in breath samples.
The findings point to human applications of this technology ...
2013-08-01
DENVER - Researchers at National Jewish Health have identified an enzyme that is essential to the allergic reaction to peanuts. Blocking the enzyme's activity in sensitized mice prevented diarrhea and inflammation, and reduced levels of several proteins associated with allergies. The findings, published online in the Journal of Allergy and Clinical Immunology, identify the enzyme, known as Cyp11a1, as a potential target for treatment of increasingly common and potentially deadly food allergy.
"Right now, we have no therapy for food allergy other than to avoid the allergenic ...
2013-08-01
Heart failure occurs when the heart cannot pump enough blood to meet the body's needs. It's a very common condition, affecting about six million people in the United States, but current therapies are not adequately effective at improving health and preventing deaths. A study published by Cell Press August 1st in the journal Cell reveals the key role of a family of molecules known as bromodomain and extraterminal domain (BET) proteins in activating genes that contribute to heart failure. The study also demonstrates that a BET-inhibiting drug can protect against heart failure ...
2013-08-01
If you have trouble going to sleep at night and waking up for work or school in the morning, a week of camping in the great outdoors might be just what you need. That's according to evidence reported on August 1 in Current Biology, a Cell Press publication, showing that humans' internal biological clocks will tightly synchronize to a natural, midsummer light-dark cycle, if only they are given the chance.
A week of exposure to true dawn and dusk with nights lit only by a campfire's glow had the biggest effect on people who might otherwise describe themselves as night owls. ...
LAST 30 PRESS RELEASES:
[Press-News.org] Blocking key enzyme in cancer cells could lead to new therapy
Researchers hope to exploit cancer's unique metabolic profile
