Featured Research

from universities, journals, and other organizations

Breaking oncogene's hold on cancer cell provides new treatment direction

Date:
January 11, 2012
Source:
Baylor College of Medicine
Summary:
Just as people's bodies and minds can become addicted to substances their cancers can become addicted to certain genes that insure their continued growth and dominance. Researchers have now developed ways to exploit the addictions of cancers to kill them without harming normal tissues.

Just as people's bodies and minds can become addicted to substances such as drugs, caffeine, alcohol, their cancers can become addicted to certain genes that ensure their continued growth and dominance.

Related Articles


Researchers at Baylor College of Medicine and Harvard Medical School have developed ways to exploit the addictions of cancers to kill them without harming normal tissues. A report on their work recently appeared online in the journal Science.

Many cancers are driven by the overexpression of oncogenes. These oncogenes are two-faced. On one hand, they promote processes that allow the cells to become immortal and to grow unchecked. On the other hand, the expression of these oncogenes creates additional anti-growth cellular stresses, conflicts that the cancer cell must subvert in order to survive.

Myc gene

One classical example of an oncogene that creates such a delicate balance is c-myc. In patients, hyper-activation of c-myc is associated with the most aggressive cancer types, with 20-40 percent of all cancers having an activated myc gene.

"For 30 years, scientists have tried to attack the oncogene myc," said Dr. Thomas Westbrook, assistant professor of molecular and human genetics and biochemistry and molecular biology at BCM and a senior author of the report. "However, it has not been amenable to the drugs we have. Now we have to take advantage of the stresses the oncogene puts on the cancer cell and determine if we can ramp those up to kill the tumor."

"Tumor cells experience considerable mitotic stress," said Westbrook. Regular chemotherapy takes advantage of this, but the drugs kill dividing cancer and normal cells. Experts think that special programs within the cancer cell allow it to cope with the stress as it grows and divides (mitosis).

"The fundamental question we asked was how are the stresses in cancer cells different from those in normal cells?" said Westbrook. "We want to exploit that idea and see if we can exacerbate that stress.

SUMO-activating enzyme

To identify genes involved in coping with this stress, Westbrook and his colleague Dr. Stephen Elledge of Harvard Medical School used a special RNA interference screen to disrupt the function of each gene in the genome and identify the genes required to allow the cancer cell to tolerate the stress of the myc oncogene.

One of the core biochemical processes they uncovered was SUMOylation, a three-step process. Westbrook, Elledge, and colleagues showed that SUMO-activating enzyme, the first step in the process, is required for myc-driven cancers to go through cell division. Thus, inhibiting SAE could be a therapeutic strategy for myc-cancers.

To test this, they turned off the SAE enzyme in a form of myc-driven breast cancer.

"The tumors stopped growing and many of them melted away," said Westbrook. Today, many of the mice are still alive and healthy. If they did not turn off production of the enzyme, the tumors grew and eventually killed the animals.

"If you inhibit this enzyme in a non-myc driven breast cancer, nothing happens," said Westbrook. "If you inhibit it in normal cells of many kinds, nothing happens."

That means that turning off SAE2 exacerbates the stress on cancer cells but not normal cells and thus be a great way to kill cancers without many of the side effects of traditional chemotherapies.

Particular importance for TNBC

The findings in this report have particular importance for an aggressive form of breast cancer called triple negative breast cancer (TNBC). This subtype is often driven by myc, and there are currently no effective treatments for these patients.

"This may provide that target," said Westbrook. The therapeutic value is that a drug targeting SAE will cause the cancer cell to no longer tolerate myc but will not be detrimental to normal cells.

In addition, myc drives many others kinds of cancers and he anticipates that inhibiting this enzyme in these tumors may have the same effect.

Others who took part in this work include Jessica D. Kessler, Tingting Sun, Kristen L. Meerbrey, Earlene M. Schmitt, Samuel O. Skinner, Mitchell Rao, Peng Yu, Rocio Dominguez-Vidana, Ronald J. Bernardi, Tiffany Hsu, Ido Golding, C. Kent Osborne, Chad J. Creighton, Susan G. Hilsenbeck, Rachel Schiff, Chad A. Shaw, all of BCM; ,Kristopher T. Kahle, Michael R. Schlabach, Qikai Xu, Mamie Z. Li, Anthony C. Liang and Nicole L. Solimini, all of Harvard and Brigham and Women's Hospital; Bing Yu and Ji Luo, both of the National Cancer Institute and Zachary C. Hartman of the University of Texas MD Anderson Cancer Center.

Funding for this work came from the National Institutes of Health, the U.S. Department of Defense, the Human Frontier Science Program, the Welch Foundation, the National Science Foundation, the Susan G. Komen for the Cure, the National Cancer Institute, the U.S. Army Innovator Award, the Howard Hughes Medical Institute, the V Foundation for Cancer Research and the Mary Kay Ash Foundation for Cancer Research.


Story Source:

The above story is based on materials provided by Baylor College of Medicine. Note: Materials may be edited for content and length.


Journal Reference:

  1. J. D. Kessler, K. T. Kahle, T. Sun, K. L. Meerbrey, M. R. Schlabach, E. M. Schmitt, S. O. Skinner, Q. Xu, M. Z. Li, Z. C. Hartman, M. Rao, P. Yu, R. Dominguez-Vidana, A. C. Liang, N. L. Solimini, R. J. Bernardi, B. Yu, T. Hsu, I. Golding, J. Luo, C. K. Osborne, C. J. Creighton, S. G. Hilsenbeck, R. Schiff, C. A. Shaw, S. J. Elledge, T. F. Westbrook. A SUMOylation-Dependent Transcriptional Subprogram Is Required for Myc-Driven Tumorigenesis. Science, 2011; DOI: 10.1126/science.1212728

Cite This Page:

Baylor College of Medicine. "Breaking oncogene's hold on cancer cell provides new treatment direction." ScienceDaily. ScienceDaily, 11 January 2012. <www.sciencedaily.com/releases/2011/12/111208141935.htm>.
Baylor College of Medicine. (2012, January 11). Breaking oncogene's hold on cancer cell provides new treatment direction. ScienceDaily. Retrieved November 20, 2014 from www.sciencedaily.com/releases/2011/12/111208141935.htm
Baylor College of Medicine. "Breaking oncogene's hold on cancer cell provides new treatment direction." ScienceDaily. www.sciencedaily.com/releases/2011/12/111208141935.htm (accessed November 20, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Thursday, November 20, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

UN Says It Will Scale Up Its Ebola Response

UN Says It Will Scale Up Its Ebola Response

AFP (Nov. 20, 2014) UN Resident Coordinator David McLachlan-Karr and WHO representative in the country Daniel Kertesz updated the media on the UN Ebola response on Wednesday. Duration: 00:51 Video provided by AFP
Powered by NewsLook.com
Takata Offers "sincerest Condolences" To Victims of Malfunctioning Airbag

Takata Offers "sincerest Condolences" To Victims of Malfunctioning Airbag

Reuters - US Online Video (Nov. 20, 2014) U.S. Congress hears from a victim and company officials as it holds a hearing on the safety of Takata airbags after reports of injuries. Rough Cut (no reporter narration). Video provided by Reuters
Powered by NewsLook.com
Obesity Costs Almost As Much As War And Terrorism

Obesity Costs Almost As Much As War And Terrorism

Newsy (Nov. 20, 2014) The newest estimate of the cost of obesity is pretty jarring — $2 trillion. But how did researchers get to that number? Video provided by Newsy
Powered by NewsLook.com
Ebola Crisis Affecting US Adoptions

Ebola Crisis Affecting US Adoptions

AP (Nov. 20, 2014) The Sanborn family had hoped they'd be able to bring home their 5-year-old adopted son from Liberia by now. But Ebola has forced them to wait. The boy is just one of thousands of orphans in West Africa who've been impacted by the deadly virus. (Nov. 20) Video provided by AP
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