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
April
 
 
 
1
LNFS Presents: Inherent Vice
Wildcat Wellness: Meditation
Successful Networking & Job Search
Tanya Habjouqa: Recent Photographs
Edward Troye: Theme & Variation
Same Difference: Michelle Grabner, Simone Leigh & Russell Maltz
Lexington Tattoo Project
Brazilian Conversation Hour
The Arboretum presents a Party for the Planet! Celebrate Kentucky's Past
Mr. PharmD Pageant 2015
Wed
2
LNFS Presents: Manakamana
LNFS Presents: Donnie Darko
National Student Exchange (NSE) Info Session
Tanya Habjouqa: Recent Photographs
Edward Troye: Theme & Variation
Same Difference: Michelle Grabner, Simone Leigh & Russell Maltz
Lexington Tattoo Project
Wildcat Wellness: Healthy Habits
SEC-ACC Virtual Career Fair
Massage on the Go #3
Thu
3
Cultural Coffee Hour
Tanya Habjouqa: Recent Photographs
Edward Troye: Theme & Variation
Same Difference: Michelle Grabner, Simone Leigh & Russell Maltz
Lexington Tattoo Project
Fri
4
Free Saturday Swing Dance Lessons
Tanya Habjouqa: Recent Photographs
Edward Troye: Theme & Variation
Same Difference: Michelle Grabner, Simone Leigh & Russell Maltz
Lexington Tattoo Project
Sat
5
Tanya Habjouqa: Recent Photographs
Edward Troye: Theme & Variation
Same Difference: Michelle Grabner, Simone Leigh & Russell Maltz
Lexington Tattoo Project
Sun
6
Wildcat Wellness: Expressions (Creative Stress Relief)
Age Friendly Community Panel
Resumes & Cover Letters that Work
Mon
7
National Student Exchange (NSE) Info Session
Wildcat Wellness: Relaxation
Tanya Habjouqa: Recent Photographs
Edward Troye: Theme & Variation
Same Difference: Michelle Grabner, Simone Leigh & Russell Maltz
Lexington Tattoo Project
Tue
8
LNFS Presents: The Godfather
Wildcat Wellness: Meditation
Internship Info Session
Tanya Habjouqa: Recent Photographs
Edward Troye: Theme & Variation
Same Difference: Michelle Grabner, Simone Leigh & Russell Maltz
Lexington Tattoo Project
Brazilian Conversation Hour
UK Remembers
SpeakBlue: Richard Sherman
Wed
9
LNFS Presents: The Shawshank Redemption
Tanya Habjouqa: Recent Photographs
Edward Troye: Theme & Variation
Same Difference: Michelle Grabner, Simone Leigh & Russell Maltz
Lexington Tattoo Project
Wildcat Wellness: Healthy Habits
From Plows to Plates: A Journey Through Kentucky Foodways
Workshop on Publishing
Teached Documentary
Thu
10
LNFS Presents: Enemy
LNFS Presents: Seven Psychopaths
Cultural Coffee Hour
Last Day to Withdraw or Reduce Course Load
Tanya Habjouqa: Recent Photographs
Edward Troye: Theme & Variation
Same Difference: Michelle Grabner, Simone Leigh & Russell Maltz
Lexington Tattoo Project
Robert C. May Photography Endowment Lecture: Julian Cox
Fri
11
Free Saturday Swing Dance Lessons
Tanya Habjouqa: Recent Photographs
Edward Troye: Theme & Variation
Same Difference: Michelle Grabner, Simone Leigh & Russell Maltz
Lexington Tattoo Project
fab-ric-ate Exhibit
Sat
12
Tanya Habjouqa: Recent Photographs
Edward Troye: Theme & Variation
Same Difference: Michelle Grabner, Simone Leigh & Russell Maltz
Lexington Tattoo Project
Kentucky's Present - Learn about the Bluegrass region of the Walk Across Kentucky and about invasive plants that threaten Kentucky landscapes
Sun
13
Wildcat Wellness: Expressions (Creative Stress Relief)
Don't Ask, Don't Tell
Get Your DIY On! Fix-It Station Demonstrations
Mon
14
Wildcat Wellness: Relaxation
Job Club - LinkedIn: Your Job Search Best Friend
Tie Dye Tuesday
#UK Kick Butts Day
Career & Major Exploration Session @ 1 p.m.
Career & Major Exploration Session @ 2 p.m.
Career & Major Exploration Session @ 3 p.m.
Take Back the Night Lexington
Tue
15
LNFS Presents: The Godfather: Part II
Wildcat Wellness: Meditation
Brazilian Conversation Hour
Career & Major Exploration Session @ 11 a.m.
Career & Major Exploration Session @ Noon
Career & Major Exploration Session @ 1 p.m.
Affrilachian Poets
Bike-In Movie: The Bicycle Thieves
Wed
16
LNFS Presents: The Perks of Being a Wallflower
Wildcat Wellness: Healthy Habits
CANCELED: Bike-In Breakfast
Human Rights in China: a panel discussion
Thu
17
LNFS Presents: North by Northwest
LNFS Presents: Raiders of the Lost Ark
Cultural Coffee Hour
Car-Free Day
Performance Conference
Audience Appeals and Performing Assistance Conference
Holi: The Indian Festival of Colors
Fri
18
Free Saturday Swing Dance Lessons
Bully Breed Awareness Walk
Spring Carnival 2015
Taste of Africa
GAYla Drag Show and Silent Auction
Sat
19
 
Sun
20
Wildcat Wellness: Expressions (Creative Stress Relief)
Floral Sculpture
Pinterest Party #3
Mon
21
Wildcat Wellness: Relaxation
Student Center "Farewell" Informational Fair
Tour de Downtown Art
Tue
22
LNFS Presents: Birdman
Wildcat Wellness: Meditation
National Student Exchange (NSE) Info Session
Brazilian Conversation Hour
Healthy Smoothie Demonstration
Ping Pong Ball Drop
Shake the Stress Fest
Wed
23
LNFS Presents: Dr. Strangelove or: How I Learned to Stop Worrying and Love the Bomb
LNFS Presents: The Avengers
Wildcat Wellness: Healthy Habits
Wildcat Wrap-Up
UK Elder Care Lunch & Learn
Kentucky's Future - Plant a Tree in the Pennyrile region of the Walk Across Kentucky
Thu
24
LNFS Presents: Batman
LNFS Presents: O Brother, Where Art Thou?
Cultural Coffee Hour
Art in Bloom Weekend
Fri
25
Free Saturday Swing Dance Lessons
Network Publishing: Digital Writing in the Humanities
The Party for the Planet final event in April is Arbor Day at The Arboretum!
Art in Bloom Weekend
Art in Bloom Cocktail Party
Sat
26
Art in Bloom Weekend
Sun
27
Resumes & Cover Letters that Work
Wildcat Wellness: Expressions (Creative Stress Relief)
Fuel for Finals
UK Ag Equine Programs Distinguished Lecture Series
Mon
28
Wildcat Wellness: Relaxation
Job Club: How to Write the Perfect Resume and Cover Letter
How to Impress Your Boss: Employer Panel
Tue
29
Wildcat Wellness: Meditation
Internship Info Session
Brazilian Conversation Hour
Appalachian Research Day
Wed
30
Wildcat Wellness: Healthy Habits
Thu
 
 

Repeats every week until Thu Apr 30 2015 except Mon Mar 16 2015.
Mon, 04/20/2015

Mon, 04/20/2015

Tue, 04/21/2015

Repeats every week until Thu Apr 30 2015 except Tue Mar 17 2015.
Tue, 04/21/2015

Reset Page