Allison Perry

Groundbreaking UK Study Shows Key Enzyme Missing from Aggressive Form of Breast Cancer

Published: Mar 25, 2013

See video

 

LEXINGTON, Ky. (March 25, 2013) – A groundbreaking new study led by the University of Kentucky Markey Cancer Center's Dr. Peter Zhou found that triple-negative breast cancer cells are missing a key enzyme that other cancer cells contain — providing insight into potential therapeutic targets to treat the aggressive cancer. Zhou's study is unique in that his lab is the only one in the country to specifically study the metabolic process of triple-negative breast cancer cells.

 

Normally, all cells — including cancerous cells — use glucose to initiate the process of making Adenosine-5'-triphosphate (ATP) for fuel to carry out essential functions. This process, called glycolysis, leads to other processes that use oxygen to make higher quantities of ATP — but solid tumor cells, which have little access to oxygen, are forced to rely almost exclusively on aerobic glycolysis for survival.  

 

Zhou's study, published in Cancer Cell, showed that the powerful transcription factor complex Snail-G9a-Dnmt1 is over-expressed in triple-negative breast cancer, inhibiting the enzyme fructose 1,6-bisphosphate (FBP1). The loss of this enzyme shuts down the glucose anabolic pathway and promotes the glucose catabolic pathway, leading to a large amount of glucose entering the tumor cells and thus "feeding" the aggressive cancer. This metabolic switch empowers the triple-negative breast cancer cells to suck more glucose from the body, increasing macromolecule biosynthesis in tumor cells and maintaining ATP production despite a dearth of nutrients and an oxygen-free environment.

 

Triple-negative breast cancer is the most deadly subtype of breast cancer, and tends to occur in women at a younger age. This subtype of breast cancer has poor clinical outcomes due to the early metastasis of tumor cells, resistance to chemotherapy, and the lack of specific drugs that target it. Identifying this change in the cancer's metabolic process provides major insight into developing drugs to target the disease, Zhou says. 

 

"These findings present significant insights regarding the development and progression of triple-negative breast cancer," said Zhou, associate professor of molecular and cellular biochemistry at UK. "They indicate that targeting the metabolic alteration will lead to an effective approach for treating this deadly disease."

 

Zhou's research was aided by the team in the Free Radical Biology in Cancer Shared Resource Facility (FRBC) of the Markey Cancer Center, directed by Dr. Allan Butterfield. The FRBC used an instrument called the Seahorse XF-96 Flux Analyzer to test and confirm the predictions of Zhou's findings in triple-negative breast cancer.

 

"The significance of this study rests in proving that triple negative breast cancer cells utilize glycolysis for survival and growth," Butterfield said. “The FRBC will assist Dr. Zhou in furthering this exciting research, potentially helping to identify key proteins in triple negative breast cancer cells that are expressed or modified differently than in control cells. Such knowledge may lead to new insights to potential approaches to treat this aggressive cancer."

 

Previously, Zhou has studied the role of the Snail complex in the cellular program known as the epithelial-mesenchymal transition (EMT), which is responsible for metastasis.

 

The study was also a collaboration with scientists at the University of Louisville (Dr. Teresa Fan) and at the University of Texas MD Anderson Cancer Center (Drs. Mien-Chie Hung and Jun Yao). 

 

 

 

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

img_0882.jpg
August
 
 
 
 
 
 
1
 
Sat
2
 
Sun
3
 
Mon
4
 
Tue
5
 
Wed
6
 
Thu
7
Curator Tour
Fri
8
 
Sat
9
 
Sun
10
 
Mon
11
 
Tue
12
 
Wed
13
 
Thu
14
 
Fri
15
 
Sat
16
 
Sun
17
 
Mon
18
We Are UK
Tue
19
 
Wed
20
 
Thu
21
Parent and Families Reception
Fri
22
K Team Meeting: K Week Overview
Big Blue U
Campus Ruckus
Getting Around Campus and Beyond
Sat
23
The Late Night Film Series Presents - Fast and Furious 7
K Team Meeting: Lunch and Campus Tour
UK Lex-Mart
Pedalpalooza
Bowman's Bash
Sun
24
Bowman's Bash
K Team Meeting: Dinner with Your K Team
Kentucky at Kroger
Mon
25
K Team Meeting: Common Reading Experience Discussion
Bicycle-Friendly Lexington
Tue
26
First Day of Classes
Don't Steal Bikes, Bro
Understanding Lexington's Bicycle Facilities
First Day of Classes
Wildcat Wellness Meditation
Wed
27
The Late Night Film Series Presents - The Wind Rises
The Late Night Film Series Presents - Avengers: Age of Ultron
Adjusting to College
Wildcat Wellness - Yoga for Relaxation
Painting and Mocktails
Terrace Time Out at the Hilary J. Boone Center
Thu
28
The Late Night Film Series Presents - Divergent
The Late Night Film Series Presents - Ex Machina
Wildcat Block Watch
Chapel Talk: Faith and Science in an Evolving World
Royalty Showcase
Fri
29
 
Sat
30
 
Sun
31
Wildcat Wellness Expressions - Inspiration Object
UK Mock Trial Informational Meeting
Mon
 
 
 
 
 

Fri, 08/28/2015

Mon, 08/31/2015

Tue, 09/01/2015

Reset Page