Featured Research

from universities, journals, and other organizations

Targeting downstream proteins in cancer-causing pathway shows promise in cell, animal model

Date:
November 13, 2012
Source:
Perelman School of Medicine at the University of Pennsylvania
Summary:
The cancer-causing form of the gene Myc alters the metabolism of mitochondria, the cell’s powerhouse, making it dependent on the amino acid glutamine for survival. Depriving cells of glutamine selectively induces programmed cell death in cells overexpressing mutant Myc. Using Myc-active neuroblastoma cells, a team three priotein executors of the glutamine-starved cell, representing a downstream target at which to aim drugs. Roughly 25 percent of all neuroblastoma cases are associated with Myc-active cells.

The cancer-causing form of the gene Myc alters the metabolism of mitochondria, the cell's powerhouse, making it dependent on the amino acid glutamine for survival. In fact, 40 percent of all "hard-to-treat" cancers have a mutation in the Myc gene.

Accordingly, depriving cells of glutamine selectively induces programmed cell death in cells overexpressing mutant Myc.

Using Myc-active neuroblastoma cancer cells, a team led by Howard Hughes Medical Institute (HHMI) investigator M. Celeste Simon, Ph.D., scientific director for the Abramson Family Cancer Research Institute (AFCRI), identified the proteins PUMA, NOXA, and TRB3 as executors of the glutamine-starved cells. These three proteins represent a downstream target in the Myc pathway at which to aim drugs. Roughly 25 percent of all neuroblastoma cases are associated with Myc-active cells.

The findings appear in this week's issue of Cancer Cell. Simon is also a professor of Cell and Developmental Biology at the Perelman School of Medicine, University of Pennsylvania. The Penn team collaborated with colleagues from The Children's Hospital of Philadelphia (CHOP) John Maris and Michael Hogarty.

"These findings come from studies of fundamental cellular pathways and would not have been discovered without ongoing support for basic research," notes Simon. "Translational research is very important, but equal emphasis on basic research of processes such as cellular metabolism is critical for the ultimate cure of cancer."

Glutamine depletion in Myc-mutant cells induces cell death through a complicated series of molecular switches involving the three protein executors and the DNA-binding protein ATF4. Knowing this, the team showed that either agonists of ATF4 or inhibitors of glutamine metabolism potently caused cell death in assays using neuroblastoma cells and inhibited tumor growth in transgenic mice. Drugs in these two classes have been approved by the Food and Drug Administration and are being tested in clinical trials for other disorders.

This study suggests that a combination of the two types of drugs might work for Myc-related neuroblastoma cancer patients.

Co-authors include Guoliang Qing, Bo Li, Nicolas Skuli, Zandra E. Walton, and David R. Wise, all from Penn, and Annette Vu, Xueyuan Liu, and Patrick A. Mayes, all from CHOP. This research was supported by the Howard Hughes Medical Institute; National Cancer Institute grants CA104838, CA097323, CA97323; an NIH F32 Training Grant 1F32CA137988 and an National Natural Science Foundation grant 81171928 from China.


Story Source:

The above story is based on materials provided by Perelman School of Medicine at the University of Pennsylvania. Note: Materials may be edited for content and length.


Journal Reference:

  1. Guoliang Qing, Bo Li, Annette Vu, Nicolas Skuli, ZandraE. Walton, Xueyuan Liu, PatrickA. Mayes, DavidR. Wise, CraigB. Thompson, JohnM. Maris, MichaelD. Hogarty, M.Celeste Simon. ATF4 Regulates MYC-Mediated Neuroblastoma Cell Death upon Glutamine Deprivation. Cancer Cell, 2012; 22 (5): 631 DOI: 10.1016/j.ccr.2012.09.021

Cite This Page:

Perelman School of Medicine at the University of Pennsylvania. "Targeting downstream proteins in cancer-causing pathway shows promise in cell, animal model." ScienceDaily. ScienceDaily, 13 November 2012. <www.sciencedaily.com/releases/2012/11/121113134230.htm>.
Perelman School of Medicine at the University of Pennsylvania. (2012, November 13). Targeting downstream proteins in cancer-causing pathway shows promise in cell, animal model. ScienceDaily. Retrieved September 16, 2014 from www.sciencedaily.com/releases/2012/11/121113134230.htm
Perelman School of Medicine at the University of Pennsylvania. "Targeting downstream proteins in cancer-causing pathway shows promise in cell, animal model." ScienceDaily. www.sciencedaily.com/releases/2012/11/121113134230.htm (accessed September 16, 2014).

Share This



More Health & Medicine News

Tuesday, September 16, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

President To Send 3,000 Military Personnel To Fight Ebola

President To Send 3,000 Military Personnel To Fight Ebola

Newsy (Sep. 16, 2014) President Obama is expected to send 3,000 troops to West Africa as part of the effort to contain Ebola's spread. Video provided by Newsy
Powered by NewsLook.com
Man Floats for 31 Hours in Gulf Waters

Man Floats for 31 Hours in Gulf Waters

AP (Sep. 16, 2014) A Texas man is lucky to be alive after he and three others floated for more than a day in the Gulf of Mexico when their boat sank during a fishing trip. (Sept. 16) Video provided by AP
Powered by NewsLook.com
Ivorians Abandon Monkey Pets in Fear Over Ebola Virus

Ivorians Abandon Monkey Pets in Fear Over Ebola Virus

AFP (Sep. 16, 2014) Since the arrival of Ebola in Ivory Coast, Ivorians have been abandoning their pets, particularly monkeys, in the fear that they may transmit the virus. Duration: 00:47 Video provided by AFP
Powered by NewsLook.com
Study Links Male-Pattern Baldness To Prostate Cancer

Study Links Male-Pattern Baldness To Prostate Cancer

Newsy (Sep. 16, 2014) New findings suggest men with a certain type of baldness at age 45 are 39 percent more likely to develop aggressive prostate cancer. Video provided by Newsy
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:
from the past week

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