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Two-faced protein can stop metastasis or promote it, researchers say

t important," he says.

Sometimes, such as during human development or wound repair, epithelial cells need to travel to other areas, and to do this, they undergo a process known as "epithelial-mesenchymal transition" (EMT). The cell reduces its production of E-cadherin proteins and increases expression of mesenchymal cadherins, thus effectively loosening the anchors that keep the cell bound to its neighbors.

Cancer, unfortunately, has adopted this strategy in order to spread, Anastasiadis says. "When the function of E-cadherin is lost in a cell, it can break free from its neighbors and travel to settle elsewhere," he says. "This means that E-cadherin normally helps suppress invasion."

But researchers have noted that the p120 catenin protein seems mysteriously two-faced: while it normally strengthens cell-cell bonding, in some cases it can also negatively affect cell adhesion. They also have found that over production of p120 increases a cell's ability to move. But the significance of these observations had eluded scientists.

In this study, Masahiro Yanagisawa, M.D., Ph.D., a research fellow in Anastasiadis' laboratory, and Anastasiadis provide an answer as to why p120 acts this way, which helps explain how the EMT shift between E-cadherin and mesenchymal cadherins allows cancer cells to break away from tissue and spread.

They found that p120 "prefers" to bind to E-cadherin, rather than to mesenchymal cadherins. So in normal epithelial cells p120 always associates with the more abundant E-cadherins. But when E-cadherin production is lost during the progression of cancer, p120 catenins begin binding to mesenchymal cadherins. And when that happens, the researchers found that p120 unexpectedly switches on a cascade of events that promote cell movement.

"We show that E-cadherin suppresses invasion, at least in part, by binding to p120 protein in the cell," Anastasiadis says. "If E-cadherin is missing, p120 is free to bind
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Source:Mayo Clinic, Jacksonville


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