Navigation Links
New UK study shows potential for targeting aggressive breast cancers
Date:2/11/2014

LEXINGTON, Ky. (Feb. 10, 2014) 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.

Jian Shi, a post-doctoral fellow at UK Markey Cancer Center, was the first author of this study, and other collaborators include UK Markey Cancer Center director Dr. Mark Evers and researchers Chi Wang and Haining Zhu. Previously, Zhou and his team have studied the role of the Snail complex also known as the cellular "brake" in contrast to Twist's accelerant in the EMT program.


'/>"/>

Contact: Allison Perry
allison.perry@uky.edu
859-323-2399
University of Kentucky
Source:Eurekalert

Related medicine news :

1. UNC study reveals potential route to bladder cancer diagnostics, treatments
2. Dartmouth study provides first global evidence that foreign aid boosts public opinion
3. Study: Resilience in parents of children undergoing stem cell transplant
4. Grant supports Cedars-Sinai study of possible links between air pollution and brain cancer
5. Study provides surprising new clue to the roots of hunger
6. Study identifies protein to repair damaged brain tissue in MS
7. Ice ages arctic tundra lush with wildflowers for woolly mammoths, study finds
8. Director of Womens Guild Lung Institute awarded grant to study treatment for lung disease
9. Columbia study finds hospitals dont follow infection prevention rules
10. Penn study reveals genetics impact risk of early menopause among some female smokers
11. New study finds feeling in control can help you live longer
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:2/27/2017)... ... February 27, 2017 , ... Robert E. Burke, MD, ... group. But his impoverished upbringing and life experiences could have led him down a ... Insightful and Inspirational Tales of Parenting, Perseverance and Pediatrics,” Dr. Burke shares a personal ...
(Date:2/27/2017)... Orange County, CA (PRWEB) , ... February 27, 2017 , ... ... for periodontitis. Periodontitis is a chronic inflammatory gum condition that occurs when the bacteria ... of deep cleaning, also referred to as a scaling and root planing or SRP, ...
(Date:2/27/2017)... ... February 27, 2017 , ... Sunshine Coast ... in British Columbia, Canada, at https://www.sunshinecoasthealthcentre.ca/ , is proud to announce the ... Mackenzie Alsager, showcases the Centre's commitment to innovation in drug rehab and alcohol ...
(Date:2/26/2017)... ... February 26, 2017 , ... Today, A' Design ... Edition of International Social Design Awards. , The 7th A' Social Design ... Governments and Institutions worldwide with realized projects and conceptual works. , The first ...
(Date:2/26/2017)... (PRWEB) , ... February 26, ... ... sets a new technology standard in staffing, scheduling, and reporting for healthcare ... and predict activity throughout the entire staffing process. StaffBridge technology improves staffing ...
Breaking Medicine News(10 mins):
(Date:2/28/2017)... Fourth-quarter 2016 revenues of $1,242 million brings ... of guidance Company reports ... associated with the write-down of goodwill and intangible assets ... Fourth-quarter reported $14.96 diluted (GAAP) ... $14.48 diluted (GAAP) loss per share from continuing operations ...
(Date:2/27/2017)... Halyard Health, Inc. (NYSE: HYH ) ... its 2017 outlook and related key planning assumptions. Executive Summary ... a 2 percent increase compared to the prior year. ... $10 million compared to net income of $15 million in ... was $24 million compared to adjusted net income of $27 ...
(Date:2/27/2017)... 27, 2017  Interpace Diagnostics Group, Inc. (NASDAQ: IDXG), ... molecular diagnostic tests and pathology services, announced today the ... upcoming United States and Canadian ... 2017 in San Antonio, Texas . ... data from the Company,s extensive experience in molecular thyroid ...
Breaking Medicine Technology: