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:2/10/2016)... ... 2016 , ... The Wickman Agency in Garland, TX has ... community. Pledging to select a new beneficiary every 60 days, the agency will ... is to bring community awareness to important local causes by forming campaigns which ...
(Date:2/10/2016)... ... February 10, 2016 , ... Dr. Peyman Ghasri, skin ... a variety of comprehensive procedures for facial enhancement. The treatments now available at ... enhancement and nasal reshaping. , As a result, patients can improve virtually ...
(Date:2/10/2016)... ... February 10, 2016 , ... Intalere’s ... together more than 200 of the country’s top healthcare executives to share insights ... true benefit of the Forum is the provider-centric perspective, experience, expertise and strategy ...
(Date:2/10/2016)... ... ... AxoGen, Inc. (NASDAQ: AXGN), a leading medical technology company focused on the peripheral ... December 31, 2015 on Monday, February 29, 2016 after the market closes. , The ... release at 4:30 PM ET. Investors interested in participating by phone are invited to ...
(Date:2/10/2016)... ... February 10, 2016 , ... Pediatric therapists ... their patients. Research shows that the Goal Attainment Scale (GAS) captures 20% more ... challenge and learn more about the Goal Attainment Scale, Education Resources Inc. is ...
Breaking Medicine News(10 mins):
(Date:2/10/2016)... Feb. 9, 2016 On Tuesday, ... (FDA) met with its Arthritis Advisory Committee ... of Johnson & Johnson,s Remicade and most ... in the U.S. The Biologics Prescribers Collaborative ... - Alliance for Patient Access, American Association ...
(Date:2/10/2016)... 2016 Demonstrates changes in ... receptor selectivity   1 receptor ... entered clinical development as a new treatment for ...   --> 1 receptor agonist, ... clinical development as a new treatment for cognitive ...
(Date:2/9/2016)... Corporation (NASDAQ: PODD ) (Insulet or the Company), the ... OmniPod ® Insulin Management System, today announced ... Insulet,s Board of Directors. With his appointment, the Board is ... --> --> Mr. Lemoine ... a deep knowledge of accounting, financial reporting and internal controls ...
Breaking Medicine Technology: