Featured Research

from universities, journals, and other organizations

Key metabolic pathway implicated in intractable form of breast cancer

Date:
July 19, 2011
Source:
Whitehead Institute for Biomedical Research
Summary:
Using a new in vivo screening system, researchers have identified a protein in a key metabolic pathway that is essential in estrogen receptor (ER)-negative breast cancer. When the expression of the gene that codes for this protein -- phosphoglycerate dehydrogenase or PHGDH -- is suppressed in tumors and cell lines with an overabundance of the protein, the rate of cellular growth declines markedly. PHGDH is overexpressed in approximately 70 percent of ER-negative breast cancer patients.

Using a new in vivo screening system, Whitehead Institute researchers have identified a protein in the serine biosynthesis pathway that is essential in estrogen receptor (ER)-negative breast cancer -- a notoriously difficult disease to treat associated with low five-year survival rates.

Related Articles


According to the researchers, when expression of the gene that codes for this protein -- phosphoglycerate dehydrogenase or PHGDH -- is suppressed in tumors and cell lines with an overabundance of the protein, the rate of cellular growth declines markedly.

As reported this month in Nature, the in vivo screen focused on 133 metabolic genes that the researchers predicted to be necessary for tumorigenesis. Using RNA interference (RNAi), first author Richard Possemato targeted these genes in human breast cancer cells implanted in mice.

"Our goal for this study was to look for essential cancer genes in vivo, where the levels of metabolites are likely more appropriate than in an in vitro model system," says Possemato, a postdoctoral researcher in the lab of Whitehead Member David Sabatini.

In vivo screening provides a more realistic understanding of what would work in a living organism rather than in a Petri dish's artificial environment. During the screen Possemato and colleagues identified PHGDH, which is overexpressed in approximately 70% of ER-negative breast cancer patients, as essential to tumor growth. The PHGDH protein is one of three enzymes involved in the metabolic serine biosynthesis pathway. Cancer cells alter their metabolism in the interest of sustaining rapid growth, and high levels of PHGDH appear to drive such metabolic change. When Possemato suppressed PHGDH protein production in breast cancer cell lines with elevated levels of it, the cells stopped proliferating.

The findings suggest that PHGDH may represent a promising target for drug development for ER-negative breast cancer.

"We do think this has some therapeutic relevance, where an inhibitors of this enzyme would have effects on the cells we identified that tend to overexpress this enzyme," says Sabatini, who is also a biology professor at MIT. "By RNAi, we've provided proof of principle, but whether a drug against this protein would be valuable remains to be determined."

This research was supported by Susan G. Komen for the Cure, Life Science Research Foundation, Keck Foundation, David H. Koch Institute for Integrative Cancer Research at MIT, The Alexander and Margaret Stewart Trust Fund, and National Institutes of Health (NIH).

Sabatini serves as a Member of the Scientific Advisory Board of Agios Pharmaceuticals.


Story Source:

The above story is based on materials provided by Whitehead Institute for Biomedical Research. The original article was written by Nicole Giese. Note: Materials may be edited for content and length.


Journal Reference:

  1. Richard Possemato, Kevin M. Marks, Yoav D. Shaul, Michael E. Pacold, Dohoon Kim, Kıvanη Birsoy, Shalini Sethumadhavan, Hin-Koon Woo, Hyun G. Jang, Abhishek K. Jha, Walter W. Chen, Francesca G. Barrett, Nicolas Stransky, Zhi-Yang Tsun, Glenn S. Cowley, Jordi Barretina, Nada Y. Kalaany, Peggy P. Hsu, Kathleen Ottina, Albert M. Chan, Bingbing Yuan, Levi A. Garraway, David E. Root, Mari Mino-Kenudson, Elena F. Brachtel, Edward M. Driggers, David M. Sabatini. Functional genomics reveal that the serine synthesis pathway is essential in breast cancer. Nature, 2011; DOI: 10.1038/nature10350

Cite This Page:

Whitehead Institute for Biomedical Research. "Key metabolic pathway implicated in intractable form of breast cancer." ScienceDaily. ScienceDaily, 19 July 2011. <www.sciencedaily.com/releases/2011/07/110718164209.htm>.
Whitehead Institute for Biomedical Research. (2011, July 19). Key metabolic pathway implicated in intractable form of breast cancer. ScienceDaily. Retrieved November 24, 2014 from www.sciencedaily.com/releases/2011/07/110718164209.htm
Whitehead Institute for Biomedical Research. "Key metabolic pathway implicated in intractable form of breast cancer." ScienceDaily. www.sciencedaily.com/releases/2011/07/110718164209.htm (accessed November 24, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Monday, November 24, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Ebola-Hit Sierra Leone's Late Cocoa Leaves Bitter Taste

Ebola-Hit Sierra Leone's Late Cocoa Leaves Bitter Taste

AFP (Nov. 23, 2014) — The arable district of Kenema in Sierra Leone -- at the centre of the Ebola outbreak in May -- has been under quarantine for three months as the cocoa harvest comes in. Duration: 01:32 Video provided by AFP
Powered by NewsLook.com
Don't Fall For Flu Shot Myths

Don't Fall For Flu Shot Myths

Newsy (Nov. 23, 2014) — Misconceptions abound when it comes to your annual flu shot. Medical experts say most people older than 6 months should get the shot. Video provided by Newsy
Powered by NewsLook.com
WFP: Ebola Risks Heightened Among Women Throughout Africa

WFP: Ebola Risks Heightened Among Women Throughout Africa

AFP (Nov. 21, 2014) — Having children has always been a frightening prospect in Sierra Leone, the world's most dangerous place to give birth, but Ebola has presented an alarming new threat for expectant mothers. Duration: 00:37 Video provided by AFP
Powered by NewsLook.com
Could Your Genes Be The Reason You're Single?

Could Your Genes Be The Reason You're Single?

Newsy (Nov. 21, 2014) — Researchers in Beijing discovered a gene called 5-HTA1, and carriers are reportedly 20 percent more likely to be single. 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:

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