Featured Research

from universities, journals, and other organizations

Interference with cellular recycling leads to cancer growth, chemo resistance

Date:
September 18, 2013
Source:
UT Southwestern Medical Center
Summary:
Overactivity of a protein that normally cues cells to divide sabotages the body’s natural cellular recycling process, leading to heightened cancer growth and chemotherapy resistance, researchers have found.

Overactivity of a protein that normally cues cells to divide sabotages the body's natural cellular recycling process, leading to heightened cancer growth and chemotherapy resistance, UT Southwestern Medical Center researchers have found.

Related Articles


The epidermal growth factor receptor, or EGFR, is found at abnormally high levels on the surface of many types of cancer cells. The study, led by Dr. Beth Levine and published Sept. 12 in Cell, revealed that EGFR turns off autophagy, a process by which cells recycle unneeded parts, by binding to a protein, Beclin 1, which normally turns on the process. The researchers found that the deactivation of autophagy by EGFR led to more rapid tumor growth and chemotherapy resistance in mice implanted with non-small lung carcinoma cells.

"The fact that this type of cell surface receptor can directly interact with Beclin 1 and shut off autophagy provides fundamental insight into how certain oncogenes may cause cancer," said Dr. Levine, director of the Center for Autophagy Research and a Howard Hughes Medical Institute (HHMI) investigator at UT Southwestern. "Our findings suggest that inactivation of autophagy may be a critically important factor in the progression of lung cancer."

Earlier work in the laboratory of Dr. Levine identified beclin 1 as the first mammalian gene shown to function in autophagy. Defects in this gene may contribute not only to cancer, but also to aging, neurodegenerative diseases, and infectious diseases.

While the link between EGFR cell signaling action and cancer growth was known, with several pharmaceutical inhibitors of EGFR already on the market to combat cancer, exactly how this process worked was a mystery. This latest research uncovers Beclin 1 as one important way in which EGFR may derail the body's cancer-fighting autophagy machinery to increase tumor growth.

A second finding in the new study related to chemotherapy resistance. Several clinical trials are currently ongoing to test inhibitors of autophagy as a means of overcoming the resistance to chemotherapeutic drugs that many tumors develop. Unexpectedly, Dr. Levine's study found just the opposite: that autophagy inhibition may actually worsen chemotherapy outcomes for patients with specific cancer mutations. The researchers showed that cancer cells with reduced autophagy grew faster and were more resistant to chemotherapy than cancer cells with normal autophagy. Dr. Levine noted that these findings may apply to many different types of cancers, especially those that rely on EGFR (or related signaling molecules) for their rapid growth.

About 10 percent of lung cancer patients have mutations in the EGFR oncogene, according to Dr. John Minna, one of the study authors and Director of the Nancy B. and Jack L. Hamon Center for Therapeutic Oncology Research and the W.A. "Tex" and Deborah Moncrief Jr. Center for Cancer Genetics at UT Southwestern. For those patients in particular, this finding could have significant impact in developing a personalized, targeted therapy.

"The EGFR protein is one of our most important targets for lung cancer therapy -- especially in patients whose tumors have certain EGFR gene mutations," Dr. Minna said. "We have oral medications that achieve dramatic clinical benefit and increase survival in this subset of patients, but even these successfully treated patients eventually become resistant to the treatment.

"These new findings are important for two reasons: First, they provide insight into how to extend EGFR-targeted therapy to a much larger group of lung cancer patients, including those whose tumors do not have mutations. Second, they provide a totally new approach to overcoming resistance to EGFR-targeted therapy."


Story Source:

The above story is based on materials provided by UT Southwestern Medical Center. Note: Materials may be edited for content and length.


Journal Reference:

  1. Yongjie Wei, Zhongju Zou, Nils Becker, Matthew Anderson, Rhea Sumpter, Guanghua Xiao, Lisa Kinch, Prasad Koduru, ChristhunesaS. Christudass, RobertW. Veltri, NickV. Grishin, Michael Peyton, John Minna, Govind Bhagat, Beth Levine. EGFR-Mediated Beclin 1 Phosphorylation in Autophagy Suppression, Tumor Progression, and Tumor Chemoresistance. Cell, 2013; 154 (6): 1269 DOI: 10.1016/j.cell.2013.08.015

Cite This Page:

UT Southwestern Medical Center. "Interference with cellular recycling leads to cancer growth, chemo resistance." ScienceDaily. ScienceDaily, 18 September 2013. <www.sciencedaily.com/releases/2013/09/130918130504.htm>.
UT Southwestern Medical Center. (2013, September 18). Interference with cellular recycling leads to cancer growth, chemo resistance. ScienceDaily. Retrieved December 21, 2014 from www.sciencedaily.com/releases/2013/09/130918130504.htm
UT Southwestern Medical Center. "Interference with cellular recycling leads to cancer growth, chemo resistance." ScienceDaily. www.sciencedaily.com/releases/2013/09/130918130504.htm (accessed December 21, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Sunday, December 21, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

The Best Tips to Curb Holiday Carbs

The Best Tips to Curb Holiday Carbs

Buzz60 (Dec. 19, 2014) It's hard to resist those delicious but fattening carbs we all crave during the winter months, but there are some ways to stay satisfied without consuming the extra calories. Vanessa Freeman (@VanessaFreeTV) has the details. Video provided by Buzz60
Powered by NewsLook.com
Sierra Leone Bikers Spread the Message to Fight Ebola

Sierra Leone Bikers Spread the Message to Fight Ebola

AFP (Dec. 19, 2014) More than 100 motorcyclists hit the road to spread awareness messages about Ebola. Nearly 7,000 people have now died from the virus, almost all of them in west Africa, according to the World Health Organization. Video provided by AFP
Powered by NewsLook.com
Researchers Test Colombian Village With High Alzheimer's Rates

Researchers Test Colombian Village With High Alzheimer's Rates

AFP (Dec. 19, 2014) In Yarumal, a village in N. Colombia, Alzheimer's has ravaged a disproportionately large number of families. A genetic "curse" that may pave the way for research on how to treat the disease that claims a new victim every four seconds. Duration: 02:42 Video provided by AFP
Powered by NewsLook.com
The Best Protein-Filled Foods to Energize You for the New Year

The Best Protein-Filled Foods to Energize You for the New Year

Buzz60 (Dec. 19, 2014) The new year is coming and nothing will energize you more for 2015 than protein-filled foods. Fitness and nutrition expert John Basedow (@JohnBasedow) gives his favorite high protein foods that will help you build muscle, lose fat and have endless energy. Video provided by Buzz60
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins