Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Tumor suppressor acts as oncogene in some cancers

Researchers at Mayo Clinic in Florida have found that a molecule long believed to be a beneficial tumor suppressor — and thus a potential cancer drug target — appears to act as an oncogene in some lethal brain tumors.

The protein, epithelial cadherin (E-cadherin), is known for its ability to keep cancer cells glued together, preventing them from breaking away and metastasizing. But, based on their findings, published online in PLoS ONE, the scientists suggest E-cadherin can also function as an oncogene in some cancers. An oncogene helps push cancer development and growth.

They say the findings could explain recent, puzzling observations about E-cadherin expression in breast cancer, for example. While loss of E-cadherin is generally considered a harbinger of metastasis, researchers have also found that most breast cancer that has spread retains E-cadherin expression. Ovarian tumors also have been paradoxically found to produce more and more E-cadherin as they grow.

"This surprising finding should compel us all to shift our thinking about E-cadherin," says the study's lead investigator, cancer biologist Panos Z. Anastasiadis, Ph.D. "Up to now, we have all thought that if a tumor loses E-cadherin function, that represents a movement toward metastasis. That makes sense because 50 percent of cancers don't express E-cadherin and they are linked to a worse prognosis.

"But now it appears that E-cadherin expression in a tumor could be responsible for cells growing out of control if the protein is not functioning as it should be."

Dr. Anastasiadis focuses his research on the biological factors involved in cancer metastasis. In this study, he and a research team, which included scientists from Mayo Clinic's campuses in Florida and Minnesota, examined protein expression in glioblastoma cancer cells. Glioblastoma is the most common, as well as the most dangerous, brain cancer.

"Our interest is to understand the pathways that induce glioblastoma to be so invasive," he says. "The problem with this cancer is that the tumors can be very aggressive, and single cancer cells can spread all over the brain."

Among other proteins, the researchers looked at cadherins, of which about 20 are expressed in the brain — more than in any other organ. These are transmembrane proteins that play critical roles in determining how cells bind to each other in a tissue. The researchers expected to find significant amounts of neural cadherin (N-cadherin) in the tumors, but not E-cadherin, which is expressed in epithelial rather that normal brain tissue.

In epithelial tissue, loss of E-cadherin usually represents a switch in cell behavior known as epithelial-mesenchymal transition (EMT). In EMT, cells that had been tightly bound to each other loosen up, due to loss of E-cadherin, and other proteins — including other members of the cadherin superfamily — then promote migration of individual cells away from a cancer cluster. Drugs are being developed that target this EMT switch, says Dr. Anastasiadis.

Given these facts, the researchers say that what they found surprised them. While N-cadherin was expressed in most human brain tumor cell lines — and N-cadherin is potentially oncogenic — some also expressed E-cadherin. They also found those cells that expressed E-cadherin acted more aggressively than brain cancer that did not express the protein. The researchers then validated their findings in animal studies. Finally, they performed an experiment in which they removed E-cadherin expression from glioblastoma cells and found these cells had a reduced ability to move, and grew at a much slower pace.

"E-cadherin expressed in these glioblastomas did not function to keep cells stuck together. Instead, they promoted tumor growth and migration," Dr. Anastasiadis says. "This is the complete opposite of what we have known about E-cadherin. For some reason, in these brain cells, E-cadherin expression is linked to aggressive cell behavior and poor prognosis."

The findings suggest "cadherins, as a whole class of proteins, need to be studied in more detail," he says. "E-cadherin expressed in glioblastoma functioned like an oncogene and it could be doing the same in many breast, ovarian, and other tumors found elsewhere in the body.

"Understanding what causes the switch in E-cadherin function from a tumor suppressor to an oncogene, and how to block it, will be critical," concludes Dr. Anastasiadis. "But the bottom line is that we cannot view E-cadherin simply as a tumor suppressor anymore."

The study was funded by the National Institutes of Health, the Accelerate Brain Cancer Cure Foundation, and a Daniel Foundation training grant. Co-authors from Mayo Clinic's sites in Florida and Minnesota include Laura Lewis-Tuffin, Ph.D., Fausto Rodriquez, M.D., Caterina Giannini, M.D., Ph.D., Bernd Scheithauer, Brian Necela, Ph.D., and Jann Sarkaria, M.D. The authors declare no conflicts of interest.

About Mayo Clinic

For more than 100 years, millions of people from all walks of life have found answers at Mayo Clinic. These patients tell us they leave Mayo Clinic with peace of mind knowing they received care from the world's leading experts. Mayo Clinic is the first and largest integrated, not-for-profit group practice in the world. At Mayo Clinic, a team of specialists is assembled to take the time to listen, understand and care for patients' health issues and concerns. These teams draw from more than 3,700 physicians and scientists and 50,100 allied staff that work at Mayo Clinic's campuses in Minnesota, Florida, and Arizona; and community-based providers in more than 70 locations in southern Minnesota, western Wisconsin and northeast Iowa. These locations treat more than half a million people each year. To best serve patients, Mayo Clinic works with many insurance companies, does not require a physician referral in most cases and is an in-network provider for millions of people. To obtain the latest news releases from Mayo Clinic, go to For information about research and education, visit ( is available as a resource for your general health information.

Kevin Punsky | EurekAlert!
Further information:

More articles from Life Sciences:

nachricht Biologists unravel another mystery of what makes DNA go 'loopy'
16.03.2018 | Emory Health Sciences

nachricht Scientists map the portal to the cell's nucleus
16.03.2018 | Rockefeller University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Locomotion control with photopigments

Researchers from Göttingen University discover additional function of opsins

Animal photoreceptors capture light with photopigments. Researchers from the University of Göttingen have now discovered that these photopigments fulfill an...

Im Focus: Surveying the Arctic: Tracking down carbon particles

Researchers embark on aerial campaign over Northeast Greenland

On 15 March, the AWI research aeroplane Polar 5 will depart for Greenland. Concentrating on the furthest northeast region of the island, an international team...

Im Focus: Unique Insights into the Antarctic Ice Shelf System

Data collected on ocean-ice interactions in the little-researched regions of the far south

The world’s second-largest ice shelf was the destination for a Polarstern expedition that ended in Punta Arenas, Chile on 14th March 2018. Oceanographers from...

Im Focus: ILA 2018: Laser alternative to hexavalent chromium coating

At the 2018 ILA Berlin Air Show from April 25–29, the Fraunhofer Institute for Laser Technology ILT is showcasing extreme high-speed Laser Material Deposition (EHLA): A video documents how for metal components that are highly loaded, EHLA has already proved itself as an alternative to hard chrome plating, which is now allowed only under special conditions.

When the EU restricted the use of hexavalent chromium compounds to special applications requiring authorization, the move prompted a rethink in the surface...

Im Focus: Radar for navigation support from autonomous flying drones

At the ILA Berlin, hall 4, booth 202, Fraunhofer FHR will present two radar sensors for navigation support of drones. The sensors are valuable components in the implementation of autonomous flying drones: they function as obstacle detectors to prevent collisions. Radar sensors also operate reliably in restricted visibility, e.g. in foggy or dusty conditions. Due to their ability to measure distances with high precision, the radar sensors can also be used as altimeters when other sources of information such as barometers or GPS are not available or cannot operate optimally.

Drones play an increasingly important role in the area of logistics and services. Well-known logistic companies place great hope in these compact, aerial...

All Focus news of the innovation-report >>>



Industry & Economy
Event News

Ultrafast Wireless and Chip Design at the DATE Conference in Dresden

16.03.2018 | Event News

International Tinnitus Conference of the Tinnitus Research Initiative in Regensburg

13.03.2018 | Event News

International Virtual Reality Conference “IEEE VR 2018” comes to Reutlingen, Germany

08.03.2018 | Event News

Latest News

Wandering greenhouse gas

16.03.2018 | Earth Sciences

'Frequency combs' ID chemicals within the mid-infrared spectral region

16.03.2018 | Physics and Astronomy

Biologists unravel another mystery of what makes DNA go 'loopy'

16.03.2018 | Life Sciences

Science & Research
Overview of more VideoLinks >>>