Two new studies provide stunning evidence suggesting that cyclin D1 – which is found in up to eight times normal amounts in half of all breast cancers – can cause a shift in the cancer cell's metabolism, changing its focus from energy production to proliferation. The findings, they say, may point to new therapeutic strategies against cancer.
Reporting last month in the journal Molecular and Cellular Biology, Kimmel Cancer Center director Richard G. Pestell, M.D., Ph.D., Professor and Chair of the Department of Cancer Biology at Jefferson Medical College, and colleagues showed for the first time that cyclin D1 – normally involved in promoting cell division – inhibits the size and activity of the cell's energy-making mitochondria.
In a separate report in August in the Proceedings of the National Academy of Sciences (PNAS), Dr. Pestell and a different team identified the mechanism behind cyclin D1's mitochondrial takeover. The research, taken together, shows that the inhibition leads to increased proliferation of cancer cells.
"From the cancer cell's point of view, the inhibition allows the cell to shift its biosynthetic priorities – it allows it to shift from making mitochondria themselves to synthesizing DNA and making the cell proliferate," says Dr. Pestell.
"Cyclin D1 shifts the individual cell's metabolism away from making mitochondria and towards cellular proliferation and the various genes involved in promoting such proliferation," he says.
The mitochondria often are called the "powerhouse" of the cell because they produce about 90 percent of the body's energy. They are located in the cytoplasm outside of each cell's nucleus.
Dr. Pestell notes that scientists have long suspected a link between mitochondrial malfunction and cancer, and since 1930 have known about such a change in metabolism when the cell turns cancerous. But the mechanisms haven't been well understood. When cells turn cancerous, they shift the way they metabolize glucose and other substrates. The researchers believe that their findings about cyclin D1 are part of such a mechanism. "These changes were observed previously," he says. "Now we know that the same factor that is involved in causing breast cancer also directly causes a metabolic shift."
I. Bernard Weinstein, M.D., Frode Jensen Professor of Medicine at Columbia University, notes that the 1930 discovery that the function of mitochondria is often impaired in cancer cells has remained unexplained and cancer research has been mainly focused on abnormalities in the function of genes in the nucleus of cells. The work by Dr. Pestell's group "provides novel insights into how these two types of abnormalities in cancer cells might be related."
In the PNAS publication, Dr. Pestell's team found that a protein, nuclear respiratory factor-1 (NRF-1), regulates a gene called mtTFA and is essential for mitochondrial
function. To make mitochondria, then, NRF-1 turns on mtTFA, which then activates genes that produce mitochondria. Cyclin D1 inactivates NRF-1, halting production.
"This discovery advances our understanding of the behavior of cancer cells and may suggest new types of cancer therapy," Dr. Weinstein says.
Dr. Pestell notes that such metabolic changes should leave the cancer cell vulnerable. "We'd like to link that change in metabolism to therapies," he says. "We've been able to prove that we can see changes in metabolism in the breast, and we should be able to target that change and kill the cancerous cells." He explains that specialists can image tumors based on changes in metabolism.
The results could also "provide a mechanism for targeting the mitochondria, rather than the nucleus," he says, noting that cancer drugs usually target nuclear genes. "Importantly, they provide a direct link between the mitochondria and the nucleus – one gene regulating both compartments of the cell. We didn't know what coordinated both functions. This shows both are functionally linked by a common gene."
"If we have therapies that target changes in metabolism, it allows us to develop therapies selective for the cancerous cells only," says Dr. Pestell.
Steve Benowitz | 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