Allison Perry

New UK Study Shows Potential for Targeting Aggressive Breast Cancers

Published: Feb 10, 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. 

 

 

MEDIA CONTACT: Allison Perry, (859) 323-2399 or allison.perry@uky.edu

zhou.jpg
November
 
 
 
 
 
 
1
Free Saturday Swing Dance Lessons
College of Pharmacy Open House
Iron Pour
UK Women's Choir 20th Anniversary Concert
Adventure Hiking & Rappelling @ Red River Gorge
Pickin' Time Mountain Music and Harvest Day
Purposeful Retirement: Planning Your Next Stage of Life
Diwali Dhoom 2014
Sat
2
UK Percussion Ensemble
Day Hike
Curator Tour: Take My Word For It
Sun
3
Industry Career Week: Resumes and Cover Letters
Kentucky Volleyball vs. Morehead State
Mon
4
Industry Career Week: How to Impress Your Boss in 90 Days
Rock Star Professionalism Series
UK Lab Band
Tue
5
Industry Career Week: Networking and Job Search
Social Enterprise and Innovation / Certified Nonprofit Professional Program Informational Meeting
Circle of Love Name Distribution
Appalachian Forum with Dr. Fran Ansley
Dana Harper Gallery Reception
Wed
6
Career Assessment Workshop
LNFS Presents: Zona Sur
LNFS Presents: The Grand Budapest Hotel
UK Jazz Ensemble
Circle of Love Name Distribution
Abstract Workshop
Lauren Potter
Thu
7
LNFS Presents: V for Vendetta
Last Day to Withdraw or Reduce Course Load
Circle of Love Name Distribution
R.C. May Photography Lecture Series: Marvin Heiferman
Men's Soccer vs. Charlotte
Kentucky Volleyball vs. Georgia
Free Friday Evening Swing Dance
Fri
8
Kentucky Football vs. Georgia
Free Saturday Swing Dance Lessons
The Power of Poetry
The Lexington Lowdown and Free Lindy Hop Workshop
Swing Dance Featuring Live music by"The Metrognomes Orchestra"
Sat
9
UK Combos Concert
Kentucky Volleyball vs. Missouri
Sun
10
Circle of Love Name Distribution
Mon
11
UK Sax Ensembles
Job Club - Interviewing Strategies
Undergraduate Research Information Session
Jose Abisambra Presentation on Current Alzheimer's Research
Women of the World: Judy Smith
Tue
12
Internship Info Session
LNFS Presents: Reservoir Dogs
Refugee Life in America
#UKEDTALKS: International Opportunities for Education Majors
Leadership Assessment
Wed
13
Career Assessment Workshop
LNFS Presents: Iron Man 3
Chili and Pie Cook-Off Supper
#TrendingTopics: Vegetarians vs. Meat-Eaters
Campus Polar Plunge to benefit Special Olympics KY
LNFS Presents: La Demora
Thu
14
LNFS Presents: Pretty in Pink
LNFS Presents: Mean Girls
Fri
15
Free Saturday Swing Dance Lessons
Sat
16
Kentucky Volleyball vs. Florida
Greek Cinematography: Critical Approach and Discussion
"Storied Streets" Documentary Showing about Experiences of Homelessness
Sun
17
The Vexillology (the study of maps) Contest
UK Rep Bands Concert
College of Agriculture, Food & Environment 2014 Celebration of Land-Grant Research
Amanda Rogers, "Black Flags, ISIS 'Swag' & Jihadi Rap: Marketing Militancy after the Arab Spring"
Stories of Homelessness: Panel Discussion
Mon
18
The Vexillology (the study of maps) Contest
A Positive Approach to Caregiving Conference
Education Abroad Open House
CatWatch Party
Appalachian Forum and Film Screening of "Up the Ridge"
Tue
19
The Vexillology (the study of maps) Contest
LNFS Presents: The Princess and the Frog
Pinterest Party
International Games Day
Global Design with Phil Duncan
Caregiver Support Group
OXFAM Social Issues Banquet
Wed
20
The Vexillology (the study of maps) Contest
Much Ado About Nothing
LNFS Presents: I Travel Because I Have To, I Come Back Because I Love You
LNFS Presents: The Big Lebowski
International Education Week Keynote Speaker: Christie Vilsack, Senior Advisor for International Education at USAID
Tobacco-free Tailgate 5 Year Anniversary
Bollywood Night
Thu
21
The Vexillology (the study of maps) Contest
Much Ado About Nothing
LNFS Presents: Water For Elephants
4th Annual Markesbery Symposium on Aging & Dementia
Freedom from Fear: On Black Childhood and Other Dangers
Bouldering @ Stone Fort
MEAT.
Fri
22
The Vexillology (the study of maps) Contest
Much Ado About Nothing
Bouldering @ Stone Fort
Free Saturday Swing Dance Lessons
Sat
23
The Vexillology (the study of maps) Contest
Much Ado About Nothing
Bouldering @ Stone Fort
UK Symphony Band and UK Concert Band
Sun
24
The Vexillology (the study of maps) Contest
Free Thanksgiving Shuttle to Blue Grass Airport
Mon
25
Free Thanksgiving Shuttle to Blue Grass Airport
Job Club - What is your money habitude?
Multicultural Student Thanksgiving Dinner
Tue
26
Thanksgiving - Academic Holidays
Free Thanksgiving Shuttle to Blue Grass Airport
Wed
27
Thanksgiving - Academic Holidays
Thu
28
Thanksgiving - Academic Holidays
Fri
29
Thanksgiving - Academic Holidays
Free Saturday Swing Dance Lessons
Kentucky Volleyball vs. Arkansas
Sat
30
 
Sun
 
 
 
 
 
 
Reset Page