Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scientists explain cancer cell metabolism changes

30.08.2006
Scientists at Jefferson Medical College and the Kimmel Cancer Center at Thomas Jefferson University in Philadelphia have found how a gene can dim the power production in the cell and in turn scale up its cancer-producing activities.

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!
Further information:
http://www.jefferson.edu

Further reports about: Cyclin Pestell cyclin D1 metabolism mitochondria proliferation

More articles from Life Sciences:

nachricht Ion treatments for cardiac arrhythmia — Non-invasive alternative to catheter-based surgery
20.01.2017 | GSI Helmholtzzentrum für Schwerionenforschung GmbH

nachricht Seeking structure with metagenome sequences
20.01.2017 | DOE/Joint Genome Institute

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Traffic jam in empty space

New success for Konstanz physicists in studying the quantum vacuum

An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Sustainable Water use in Agriculture in Eastern Europe and Central Asia

19.01.2017 | Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

 
Latest News

Helmholtz International Fellow Award for Sarah Amalia Teichmann

20.01.2017 | Awards Funding

An innovative high-performance material: biofibers made from green lacewing silk

20.01.2017 | Materials Sciences

Ion treatments for cardiac arrhythmia — Non-invasive alternative to catheter-based surgery

20.01.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>