Mayo Clinic researchers find “two faced” protein critical to breast cancer spread
Remarkably, fewer researchers than one might think focus on how it is that cancer spreads from an initial tumor, say in the breast, to distant organs and sites, like the bones and brain. It is, after all, this distant spread that makes cancer so very deadly - about 95% of patients who succumb to cancer do so as a result of metastasis - but many scientists aim to halt cancer before it leaves the tumor.
Still, metastasis happens, even in the setting of advanced cancer treatment, so a group of researchers at the Mayo Clinic in Jacksonville have made it their goal to understand this initial movement of cancer from the first tumor that develops. Just how is it that a single cell, or several, can unlatch itself from the closely woven network of cells in a breast tumor to sail through the blood or lymph system to a new home?
Now, Mayo Clinic researcher Panos Anastasiadis, Ph.D, has found that a single protein acts as a deadly “master switch,” both freeing cancer cells from a tumor while promoting their new growth.
This is potentially good news, says Dr. Anastasiadis and his research team, who published their study in the November 17 issue of the Journal of Cell Biology. If this one molecule – known as p120 catenin - is that powerful, it may be possible to turn the tables on cancer by designing an agent that would suppress it.
“We believe p120 could be an excellent target for therapy,” says Dr. Anastasiadis, the study’s lead investigator. “Most cancer therapies target cancer growth, but miss migrating cancer cells that eventually re-establish the tumor often at distant sites. Our best hope for long-term cancer therapy is to target both cancer cell growth and tumor spread, or metastasis.
“An anti-p120 agent could provide a much needed double whammy – stop cancer spread and shut down growth at the same time,” he says.
Dr. Anastasiadis says that the discovery was made in breast cancer cells by a team of collaborating researchers that includes Edith Perez, M.D., a Mayo oncologist in the Breast Cancer Program who has played an integral role in the 26.2 with Donna: The National Marathon to Fight Breast Cancer.
Dr. Anastasiadis had earlier discovered that p120 activity is necessary if cancer is to spread. But they did not know about its role in growth promotion until this latest work.
p120 acts in cells by regulating the function of proteins called cadherins, which help cells stick to each other like Velcro to form tissue. The best understood of the cadherins is E-cadherin, which binds all epithelial cells to each other, forming layers that cover the inside of organs and body cavities, and the outside skin of humans. In short, E-cadherin holds a human’s cells and tissues together, Dr. Anastasiadis says.
In this study, the researchers discovered that not only does p120 promote metastasis when it is not bound to E-cadherin, it also turns on growth-promoting genes and proteins. In laboratory and animal experiments, they found that “free” p120 makes cancer very aggressive, able to grow in conditions that other cancer cells can’t.
“What is really interesting here is that p120 is acting like a tumor suppressor when it is bound to E-cadherin, and like a tumor promoter when it isn’t,” Dr. Anastasiadis says.
The researchers believe these findings could help explain why in some solid tumors, such as breast, loss of E-cadherin is associated with a more aggressive, less treatable prognosis.
“So in breast cancer that is HER2-positive, anti-HER2 therapies such as Herceptin will not function well if p120 has turned on alternate growth mechanisms,” Dr. Anastasiadis says.
A potential solution would be to design an agent that targets the tumor promoting function of p120 that is not bound to E-cadherin, he says. “This won’t be easy, but based on our current understanding of p120 function we believe it is possible.”
