Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Study Reveals Interference with Cellular Recycling Leads to Cancer Growth, Chemotherapy Resistance

23.09.2013
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.

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 inactivation 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.”

Other UT Southwestern researchers involved in the study were lead author Dr. Yongjie Wei, assistant professor of internal medicine; Zhongju Zou, HHMI research specialist; Dr. Nils Becker, a former research assistant in internal medicine; Dr. Matthew Anderson, a former postdoctoral researcher in internal medicine; Dr. Rhea Sumpter, instructor of internal medicine; Dr. Guanghua Xiao, associate professor of clinical sciences; Dr. Lisa Kinch, bioinformatics scientist in biochemistry; Dr. Prasad Koduru, professor of pathology; Dr. Nick Grishin, professor of biophysics and biochemistry and an HHMI investigator; and Dr. Michael Peyton, a senior research scientist in the Hamon Center for Therapeutic Oncology Research. Researchers from Johns Hopkins University School of Medicine and Columbia University Medical Center also participated.

The research was supported by three grants from the National Institutes of Health, including a Lung Cancer SPORE (Specialized Program of Research Excellence) grant from the National Cancer Institute.

About UT Southwestern Medical Center

UT Southwestern, one of the premier academic medical centers in the nation, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty has many distinguished members, including five who have been awarded Nobel Prizes since 1985. Numbering more than 2,700, the faculty is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide medical care in 40 specialties to nearly 90,000 hospitalized patients and oversee more than 1.9 million outpatient visits a year.

This news release is available on our home page at utsouthwestern.edu/home/news/index.html

To automatically receive news releases from UT Southwestern via email, subscribe at UT Southwestern.edu/receivenews

Debbie Bolles | New
Further information:
http://www.utsouthwestern.edu

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Can we see monkeys from space? Emerging technologies to map biodiversity

An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.

Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

Supersensitive through quantum entanglement

28.06.2017 | Physics and Astronomy

X-ray photoelectron spectroscopy under real ambient pressure conditions

28.06.2017 | Physics and Astronomy

Mice provide insight into genetics of autism spectrum disorders

28.06.2017 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>