Cell Movement Mechanism May Provide Clues to Containing Metastasis

Author:  Neil Majithia
Institution:  Virginia Commonwealth University
Date:  October 2008

The Institute for Research in Biomedicine (IRB Barcelona), in conjunction with Instituto de Biología Molecular, has characterized a mechanism of cell movement that involves the regulation of cell-to-cell adhesion. The report, which was published in the August 2008 edition of Nature Cell Biology, suggests that defects in the cell adhesion mechanism might be responsible for the lethal metastatic migration of cancer cells.

The conclusions were based on a study of tracheal development in Drosophila flies. During development, cells originally found in columnar arrangement reposition themselves and line up in a "single file" manner. An important regulator of this cellular movement is E-Cadherin, a membrane protein involved in cell adhesion.

"When movement starts, the levels of this protein in the cells decrease, thereby allowing them to slide one on top of the other, and once in this position the levels of this protein are re-established in order to seal the new binding alignment. The sequence is clear: the greater the amount of protein, the greater the adhesion and the smaller the movement," said Jordi Casanova, one of the authors of the study.

Since E-Cadherin is made inside the cells before being incorporated into the membrane, manipulating E-Cadherin production was an effective way to alter cell migration. The team found that by tampering with the intracellular elements responsible for trafficking E-Cadherin from organelles to the membrane they could alter a cell's pattern of movement.

E-Cadherin is known to bind together epithelial cells of all animals, so the investigators speculate the intracellular mechanism of its regulation may also be universal.

"We speculate that the regulatory mechanism that we have discovered may also be present in other developmental contexts. However, in addition, fundamental elements of the mechanism may show a dysfunction in pathological processes such as the progression of cancer and metastases," said Casanova.

In a previous study Casanova's team had shown that the amount of E-Cadherin and intracellular elements responsible for its trafficking decreased with the progression of a certain type of esophageal cancer, allowing the tumor to migrate and move to surrounding tissues. The next goal for the research team is to use various in vivo cancer models to search for defects in the E-Cadherin trafficking pathway and determine whether they correlate with malignant cell migration.

Written by Neil Majithia

Edited by Pooja Ghatalia

Published by Hoi See Tsao