Featured Research

from universities, journals, and other organizations

Critical pathway in cell cycle may lead to cancer development

Date:
July 11, 2013
Source:
Salk Institute for Biological Studies
Summary:
Researchers' findings on chromosome shortening suggest a potential target to arrest cancer cell growth.

From left are Salk scientists Makoto Hayashi, Anthony Cesare and Jan Karlseder.
Credit: Image: Courtesy of the Salk Institute for Biological Studies

A team of scientists at the Salk Institute for Biological Studies has identified why disruption of a vital pathway in cell cycle control leads to the proliferation of cancer cells. Their findings on telomeres, the stretches of DNA at the ends of chromosomes that protect our genetic code and make it possible for cells to divide, suggest a potential target for preventive measures against cancer, aging and other diseases.

Related Articles


The findings were published July 11 in Molecular Cell.

Telomeres have been compared to the plastic tips at the end of shoelaces because they prevent the ends of chromosomes from fraying and sticking to each other, which scrambles the genetic information and may promote cancer. They are crucial to DNA replication, tumor suppression and aging. Each time a human cell divides, its telomeres become shorter. When they become too short, the cell can no longer divide and becomes inactive, or "senescent," or dies. Cells can escape this fate by activating an enzyme called telomerase, which prevents telomeres from getting shorter and allows the cells to continue to grow and divide. Uncontrolled cellular growth is a primary hallmark of cancer cells, and shortened telomeres have been identified in pancreatic, bone, prostate, bladder, lung, kidney and head and neck cancers.

"As telomeres shorten during normal [cellular] aging, they activate a DNA damage response to arrest cell growth, which protects our DNA from harm," says senior study author Jan Karlseder, a professor in Salk's Molecular and Cell Biology Laboratory and holder of the Donald and Darlene Shiley Chair.

Karlseder and his team identified that cell growth arrest due to shortening telomeres is confined to one specific portion of the cell cycle, called the G1 phase, which is the most protected stage of the cell cycle. "The pathway controlling G1-phase growth arrest, however, is commonly altered in cancer cells, allowing cancer cells to divide despite shortened telomeres, which can lead to the genomic instability seen in malignant cells."

In the study, Karlseder and his colleagues mimicked the process of cellular aging by partially removing a protein called TRF2 from the telomeres of human fibrosarcoma (a type of cancer that affects connective tissue) cells. By doing so, they were able to experimentally reproduce the process that occurs naturally as cells age. This telomere "deprotection" exposed the ends of chromosomes during certain stages of the cell cycle. In this state, they found that telomeres exhibited a partial DNA damage response: the ends of chromosomes were protected against fusing and fraying, but cell growth was still arrested.

"Basically," says lead author Anthony Cesare, a research associate in Karlseder's laboratory, "there's cell growth arrest without genomic instability. Thus, telomere aging, in normal, healthy cells and living organisms, means cell arrest, but no harmful genetic effects."

The Salk scientists identified the p53 pathway, a molecular mechanism that normally protects a cell's genetic material and suppresses tumors, as the key player in the response to telomere deprotection. When cells lose the function of p53, the gene at the center of the pathway, they can no longer arrest cells in the G1 phase, an important point in the cell cycle for repairing DNA damage or, if the damage cannot be repaired, targeting the cell for programmed death. Most commonly, p53 is lost in cancer cells due to a mutation in the p53 gene or the inactivation of p53 protein function through infection from cancer-causing viruses.

Because telomere deprotection results in a partial DNA damage response that only arrests cells in G1 through the p53 pathway, once cells lose p53 function telomere deprotection no longer arrests growth. "Cells without functional p53 are able to divide with deprotected telomeres, which causes genomic instability, a common feature of malignant cells," says Karlseder.

Karlseder and his colleagues believe that better understanding the telomere shortening process may lead to the ability to influence cellular aging and, as a result, stunt cancer cell growth. They say the next step is determining why this deprotection response is muted in cancer cells, and possibly affecting this process to prevent cancer cells from growing.

Other researchers on the study were Makoto T. Hayashi and Laure Crabbe of the Salk Institute. The work was supported by the National Institutes of Health, the John Sabo Trust, the Highland Street Foundation, the Human Frontier Science Program, the Japan Society for the Promotion of Science and the Salk Institute Glenn Center for Aging.


Story Source:

The above story is based on materials provided by Salk Institute for Biological Studies. Note: Materials may be edited for content and length.


Journal Reference:

  1. AnthonyJ. Cesare, MakotoT. Hayashi, Laure Crabbe, Jan Karlseder. The Telomere Deprotection Response Is Functionally Distinct from the Genomic DNA Damage Response. Molecular Cell, 2013; DOI: 10.1016/j.molcel.2013.06.006

Cite This Page:

Salk Institute for Biological Studies. "Critical pathway in cell cycle may lead to cancer development." ScienceDaily. ScienceDaily, 11 July 2013. <www.sciencedaily.com/releases/2013/07/130711135223.htm>.
Salk Institute for Biological Studies. (2013, July 11). Critical pathway in cell cycle may lead to cancer development. ScienceDaily. Retrieved December 21, 2014 from www.sciencedaily.com/releases/2013/07/130711135223.htm
Salk Institute for Biological Studies. "Critical pathway in cell cycle may lead to cancer development." ScienceDaily. www.sciencedaily.com/releases/2013/07/130711135223.htm (accessed December 21, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Sunday, December 21, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

The Best Tips to Curb Holiday Carbs

The Best Tips to Curb Holiday Carbs

Buzz60 (Dec. 19, 2014) It's hard to resist those delicious but fattening carbs we all crave during the winter months, but there are some ways to stay satisfied without consuming the extra calories. Vanessa Freeman (@VanessaFreeTV) has the details. Video provided by Buzz60
Powered by NewsLook.com
Sierra Leone Bikers Spread the Message to Fight Ebola

Sierra Leone Bikers Spread the Message to Fight Ebola

AFP (Dec. 19, 2014) More than 100 motorcyclists hit the road to spread awareness messages about Ebola. Nearly 7,000 people have now died from the virus, almost all of them in west Africa, according to the World Health Organization. Video provided by AFP
Powered by NewsLook.com
Researchers Test Colombian Village With High Alzheimer's Rates

Researchers Test Colombian Village With High Alzheimer's Rates

AFP (Dec. 19, 2014) In Yarumal, a village in N. Colombia, Alzheimer's has ravaged a disproportionately large number of families. A genetic "curse" that may pave the way for research on how to treat the disease that claims a new victim every four seconds. Duration: 02:42 Video provided by AFP
Powered by NewsLook.com
The Best Protein-Filled Foods to Energize You for the New Year

The Best Protein-Filled Foods to Energize You for the New Year

Buzz60 (Dec. 19, 2014) The new year is coming and nothing will energize you more for 2015 than protein-filled foods. Fitness and nutrition expert John Basedow (@JohnBasedow) gives his favorite high protein foods that will help you build muscle, lose fat and have endless energy. Video provided by Buzz60
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins