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.
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.
Sharon Parmet | EurekAlert!
Multi-institutional collaboration uncovers how molecular machines assemble
02.12.2016 | Salk Institute
Fertilized egg cells trigger and monitor loss of sperm’s epigenetic memory
02.12.2016 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.
The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...
Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water
In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...
The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.
Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
02.12.2016 | Medical Engineering
02.12.2016 | Agricultural and Forestry Science
02.12.2016 | Physics and Astronomy