Scientists find genetic link between cancer and premature aging

June 26, 2003

SEATTLE - Biologists have long known that the promise of eternal youth comes with a hefty price tag, a truth borne out by the immortality of most cancer cells.

The link between aging and cancer is now clearer thanks to a new study that connects a powerful cancer-causing protein to a gene associated with Werner syndrome, a disease that causes premature aging.

Carla Grandori, M.D., Ph.D., of Fred Hutchinson Cancer Research Center, and colleagues report in the July issue of Genes & Development that the cancer-promoting activity of Myc - a protein implicated in breast, prostate and many other tumors - depends in part on its ability to activate the WRN gene, whose absence leads to Werner's syndrome.

Based on their results, Grandori and co-investigators at Fred Hutchinson, the University of Washington School of Medicine and Columbia University speculate that a novel class of anti-cancer therapies might be developed based on drugs that interfere with the anti-aging properties of the WRN gene.

Werner syndrome is a rare genetic disorder that develops when the WRN gene is missing or defective. The disease causes the onset of premature aging shortly after puberty and results in the appearance of old age when patients are 30 to 40 years of age. The syndrome is thought to occur because mutations in WRN cause genetic instability, a condition in which chromosomes are dramatically rearranged. Because genetic instability is also a common feature of tumor cells, Werner patients often die prematurely of cancers.

But the cancers that result from loss of the WRN gene differ from the tumors that are triggered by Myc, which require an intact WRN gene, said Grandori, a staff scientist in Fred Hutchinson's Human Biology Division and lead author of the paper.

"No one had implicated the Werner syndrome gene as a general pro-tumor agent," she said. "Patients with Werner do develop cancers, but they are very rare cancers and tend to occur later in a patient's life. They don't develop Myc-related cancers, and our findings help to explain why."

Myc already had been known to cause cell immortality, a characteristic that enables tumors to grow indefinitely. Grandori and colleagues in Riccardo Dalla-Favera's laboratory at Columbia University discovered in 1999 that Myc switches on telomerase, an enzyme that extends the lifespan of cells.

"Although telomerase is important for immortalizing cells, it's not sufficient in all cell types," she said. "We asked, 'What other gene could be important for preventing senescence?' The Werner syndrome gene was an obvious candidate."

Using human cells grown in the laboratory, Grandori found that when Myc was overproduced, activity of the Werner syndrome gene was similarly induced and cells became immortalized.

In cells in which the Werner syndrome gene was missing, an overabundance of Myc caused the cells to rapidly age. Aging cells have a flat appearance, stop dividing and have a unique pattern of gene expression.

Grandori said the these results suggest that it may be possible to block Myc's tumor-promoting activity by inhibiting the WRN gene, which would cause the cells to begin the aging process and cease to grow. She speculates that such drugs would be unlikely to mimic the symptoms of Werner syndrome.

"If cancer cells have higher levels of WRN than normal cells, tumor cells are likely to be more susceptible than healthy cells to drugs that inhibit WRN, so that normal cells would be relatively unaffected by the treatment." she said. "This could be a new approach for treating many cancers, since Myc is associated with numerous tumor types."
This research was funded by grants from the National Institutes of Health and the Nippon Boehringer-Ingelheim Virtual Research Institute on Aging.

The Fred Hutchinson Cancer Research Center, home of two Nobel Prize laureates, is an independent, nonprofit research institution dedicated to the development and advancement of biomedical technology to eliminate cancer and other potentially fatal diseases. Fred Hutchinson receives more funding from the National Institutes of Health than any other independent U.S. research center. Recognized internationally for its pioneering work in bone-marrow transplantation, the center's four scientific divisions collaborate to form a unique environment for conducting basic and applied science. Fred Hutchinson, in collaboration with its clinical partners, the University of Washington Academic Medical Center and Children's Hospital and Regional Medical Center, is the only National Cancer Institute-designated comprehensive cancer center in the Pacific Northwest and is one of 39 nationwide. For more information, visit the center's Web site at

Fred Hutchinson Cancer Research Center

Related Cancer Articles from Brightsurf:

New blood cancer treatment works by selectively interfering with cancer cell signalling
University of Alberta scientists have identified the mechanism of action behind a new type of precision cancer drug for blood cancers that is set for human trials, according to research published in Nature Communications.

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.

Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.

More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.

New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.

American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.

Read More: Cancer News and Cancer Current Events 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