Featured Research

from universities, journals, and other organizations

Potential for targeting aggressive breast cancers

Date:
February 11, 2014
Source:
University of Kentucky
Summary:
A new study shows that targeting Twist, a nuclear protein that is an accelerant of the epithelial-mesenchymal transition (EMT) program in human cells, may provide an effective approach for treating triple-negative breast cancer.

A new study led by University of Kentucky Markey Cancer Center researcher Peter Zhou shows that targeting Twist, a nuclear protein that is an accelerant of the epithelial-mesenchymal transition (EMT) program in human cells, may provide an effective approach for treating triple-negative breast cancer.

Triple-negative breast cancer has an activated EMT program, which is a process that provides cells with the increased plasticity (or flexibility) to adapt to stressed environments during embryonic development, wound healing, tissue fibrosis and metastasis. EMT provides tumor cells with stem cell-like characteristics, making them resistant to therapeutics and increasing their chances for early metastasis.

Triple-negative breast cancer in particular is associated with an aggressive clinical history, development of recurrence, distant metastasis and shorter patient survival, especially in younger women. It lacks effective targeted therapies and often displays early metastatic spread to brain and lung, sites known to be associated with an estimated 5-year survival of less than 20 percent.

Published in Cancer Cell, the study found that the nuclear protein Twist acts similarly to a virus protein. Using protein purification, Zhou's team identified that Twist interacted with a key nuclear transcription regulator BRD4. When many DNA viruses (such as papillomaviruses) enter into human "host" cells during infection, they hijack host cell machinery to replicate and synthesis their viral DNA and proteins. BRD4 is the virus's favored molecule and is often seized by DNA papillomaviruses for gene transcription during replication and growth.

Twist uses a similar strategy to recruit BRD4 to the genomic regions that are regulated by Twist. Many of these genomic regions contain oncogenes, such as those of survival proteins, growth factors and molecules that enhance cell migration and invasion. By recruiting BRD4 to these genomic regions, Twist accelerates cell growth and invasion by "waking up" the expression of these oncogenes.

Additionally, the study showed that two BRD4 inhibitors, JQ1 and MS417, can specifically disrupt the interaction of Twist with BRD4, resulting in the suppression of invasion, stem cell-like characters and tumorigenicity of triple-negative breast cancer cells.

"This finding has significant clinical ramification, because drugs that can target the Twist-BRD4 interaction provide a new hope for treating life-threatening triple-negative breast cancer," said Zhou, associate professor of molecular and cellular biochemistry at UK.


Story Source:

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


Journal Reference:

  1. Jian Shi, Yifan Wang, Lei Zeng, Yadi Wu, Jiong Deng, Qiang Zhang, Yiwei Lin, Junlin Li, Tiebang Kang, Min Tao, Elena Rusinova, Guangtao Zhang, Chi Wang, Haining Zhu, Jun Yao, Yi-Xin Zeng, B.Mark Evers, Ming-Ming Zhou, BinhuaP. Zhou. Disrupting the Interaction of BRD4 with Diacetylated Twist Suppresses Tumorigenesis in Basal-like Breast Cancer. Cancer Cell, 2014; 25 (2): 210 DOI: 10.1016/j.ccr.2014.01.028

Cite This Page:

University of Kentucky. "Potential for targeting aggressive breast cancers." ScienceDaily. ScienceDaily, 11 February 2014. <www.sciencedaily.com/releases/2014/02/140211174615.htm>.
University of Kentucky. (2014, February 11). Potential for targeting aggressive breast cancers. ScienceDaily. Retrieved October 20, 2014 from www.sciencedaily.com/releases/2014/02/140211174615.htm
University of Kentucky. "Potential for targeting aggressive breast cancers." ScienceDaily. www.sciencedaily.com/releases/2014/02/140211174615.htm (accessed October 20, 2014).

Share This



More Health & Medicine News

Monday, October 20, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

How Nigeria Beat Its Ebola Outbreak

How Nigeria Beat Its Ebola Outbreak

Newsy (Oct. 20, 2014) The World Health Organization has declared Nigeria free of Ebola. Health experts credit a bit of luck and the government's initial response. Video provided by Newsy
Powered by NewsLook.com
Another Study Suggests Viagra Is Good For The Heart

Another Study Suggests Viagra Is Good For The Heart

Newsy (Oct. 20, 2014) An ingredient in erectile-dysfunction medications such as Viagra could improve heart function. Perhaps not surprising, given Viagra's history. Video provided by Newsy
Powered by NewsLook.com
Ebola Worries End for Dozens on U.S. Watch Lists

Ebola Worries End for Dozens on U.S. Watch Lists

Reuters - US Online Video (Oct. 20, 2014) Forty-three people who had contact with Thomas Eric Duncan, the first person diagnosed with Ebola in the U.S., were cleared overnight of twice-daily monitoring after 21 days of showing no symptoms. Rough Cut (no reporter narration). Video provided by Reuters
Powered by NewsLook.com
Fauci: Ebola Protocols to Focus on Training

Fauci: Ebola Protocols to Focus on Training

AP (Oct. 20, 2014) Dr. Anthony Fauci, head of the National Institute of Allergy and Infectious Diseases, says he expects revised CDC protocols on Ebola to focus on training, observation and ensuring health care workers are more protected. (Oct. 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