Key enzyme plays roles as both friend and foe to cancer

June 13, 2012

A molecule thought to limit cell proliferation also helps cancer cells survive during initial tumor formation and when the wayward cells spread to other organs in the body, researchers at the University of Illinois at Chicago College of Medicine have found.

The study was published in the May 31 issue of Nature.

The new study seems to contradict earlier findings that activation of the enzyme, called AMP-activated protein kinase, or AMPK, inhibits the growth of cells in culture.

Because of its role in inhibiting cancer cell growth and proliferation, AMPK has been viewed as a promising potential target for developing new chemotherapy drugs, says Nissim Hay, professor of biochemistry and molecular genetics at UIC and principle investigator on the study.

But Hay and his colleagues found that when the cell is under metabolic stress, AMPK is activated to promote cell survival and prevent cell death.

"Paradoxically, activated AMPK is actually required for the survival of the cancer cell during metabolic stress, when glucose uptake is decreased," Hay said. Cancer cells are subjected to metabolic stress when they first leave the cell matrix to form a solid tumor, and again when they migrate out of the tumor to spread throughout the body.

The researchers found that AMPK promotes the survival of cancer cells by indirectly regulating NADPH, a molecule that reduces harmful reactive-oxygen species. They showed that AMPK exerts it effect by regulating enzymes that control fatty acid synthesis and fatty acid oxidation.

The new study may also help to explain a previous unexpected finding: that cells that are deficient in AMPK, or in another enzyme that is responsible for activating AMPK, called LKB1, are resistant to becoming cancerous. Patients with Peuta-Jeghers syndrome, an inherited deficiency of LKB1, develop only benign tumors incapable of spreading.

AMPK, through its role in limiting proliferation, may still offer a promising target for chemotherapy, Hay said, but it would be important to target the fatty acid synthesis enzymes at the same time in order to block AMPK's protective effect.

The study was supported by grants from the National Institutes of Health; the Chicago Biomedical Consortium with support from The Searle Funds at The Chicago Community Trust; and the Diabetes Research and Training Center at the University of Chicago.

Sang-Min Jeon, former UIC graduate student, is first author on the study. He is now on staff at Genetech in San Francisco. Navdeep Chandel, professor of pulmonary and critical care medicine at Northwestern University, also contributed to the study.
-end-
[Editors note: images available at newsphoto.lib.uic.edu/v/Hay/hay.jpg.html. ]

For more information about the University of Illinois Hospital & Health Sciences System, visit www.hospital.uillinois.edu

University of Illinois at Chicago

Related Cancer Cells Articles from Brightsurf:

Cancer researchers train white blood cells to attacks tumor cells
Scientists at the National Center for Tumor Diseases Dresden (NCT/UCC) and Dresden University Medicine, together with an international team of researchers, were able to demonstrate that certain white blood cells, so-called neutrophil granulocytes, can potentially - after completing a special training program -- be utilized for the treatment of tumors.

New way to target some rapidly dividing cancer cells, leaving healthy cells unharmed
Scientists at Johns Hopkins Medicine and the University of Oxford say they have found a new way to kill some multiplying human breast cancer cells by selectively attacking the core of their cell division machinery.

Breast cancer cells use message-carrying vesicles to send oncogenic stimuli to normal cells
According to a Wistar study, breast cancer cells starved for oxygen send out messages that induce oncogenic changes in surrounding normal epithelial cells.

Breast cancer cells turn killer immune cells into allies
Researchers at Johns Hopkins University School of Medicine have discovered that breast cancer cells can alter the function of immune cells known as Natural killer (NK) cells so that instead of killing the cancer cells, they facilitate their spread to other parts of the body.

Breast cancer cells can reprogram immune cells to assist in metastasis
Johns Hopkins Kimmel Cancer Center investigators report they have uncovered a new mechanism by which invasive breast cancer cells evade the immune system to metastasize, or spread, to other areas of the body.

Engineered immune cells recognize, attack human and mouse solid-tumor cancer cells
CAR-T therapy has been used successfully in patients with blood cancers such as lymphoma and leukemia.

Drug that keeps surface receptors on cancer cells makes them more visible to immune cells
A drug that is already clinically available for the treatment of nausea and psychosis, called prochlorperazine (PCZ), inhibits the internalization of receptors on the surface of tumor cells, thereby increasing the ability of anticancer antibodies to bind to the receptors and mount more effective immune responses.

Engineered bone marrow cells slow growth of prostate and pancreatic cancer cells
In experiments with mice, researchers at the Johns Hopkins Kimmel Cancer Center say they have slowed the growth of transplanted human prostate and pancreatic cancer cells by introducing bone marrow cells with a specific gene deletion to induce a novel immune response.

First phase i clinical trial of CRISPR-edited cells for cancer shows cells safe and durable
Following the first US test of CRISPR gene editing in patients with advanced cancer, researchers report these patients experienced no negative side effects and that the engineered T cells persisted in their bodies -- for months.

Zika virus' key into brain cells ID'd, leveraged to block infection and kill cancer cells
Two different UC San Diego research teams identified the same molecule -- αvβ5 integrin -- as Zika virus' key to brain cell entry.

Read More: Cancer Cells News and Cancer Cells Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.