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 Climate Impact Research in Hannover: Small Plants against Large Waves
17.08.2018 | Leibniz Universität Hannover

nachricht First transcription atlas of all wheat genes expands prospects for research and cultivation
17.08.2018 | Leibniz-Institut für Pflanzengenetik und Kulturpflanzenforschung

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Color effects from transparent 3D-printed nanostructures

New design tool automatically creates nanostructure 3D-print templates for user-given colors
Scientists present work at prestigious SIGGRAPH conference

Most of the objects we see are colored by pigments, but using pigments has disadvantages: such colors can fade, industrial pigments are often toxic, and...

Im Focus: Unraveling the nature of 'whistlers' from space in the lab

A new study sheds light on how ultralow frequency radio waves and plasmas interact

Scientists at the University of California, Los Angeles present new research on a curious cosmic phenomenon known as "whistlers" -- very low frequency packets...

Im Focus: New interactive machine learning tool makes car designs more aerodynamic

Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.

When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...

Im Focus: Robots as 'pump attendants': TU Graz develops robot-controlled rapid charging system for e-vehicles

Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.

Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....

Im Focus: The “TRiC” to folding actin

Proteins must be folded correctly to fulfill their molecular functions in cells. Molecular assistants called chaperones help proteins exploit their inbuilt folding potential and reach the correct three-dimensional structure. Researchers at the Max Planck Institute of Biochemistry (MPIB) have demonstrated that actin, the most abundant protein in higher developed cells, does not have the inbuilt potential to fold and instead requires special assistance to fold into its active state. The chaperone TRiC uses a previously undescribed mechanism to perform actin folding. The study was recently published in the journal Cell.

Actin is the most abundant protein in highly developed cells and has diverse functions in processes like cell stabilization, cell division and muscle...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

LaserForum 2018 deals with 3D production of components

17.08.2018 | Event News

Within reach of the Universe

08.08.2018 | Event News

A journey through the history of microscopy – new exhibition opens at the MDC

27.07.2018 | Event News

 
Latest News

Smallest transistor worldwide switches current with a single atom in solid electrolyte

17.08.2018 | Physics and Astronomy

Robots as Tools and Partners in Rehabilitation

17.08.2018 | Information Technology

Climate Impact Research in Hannover: Small Plants against Large Waves

17.08.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>