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Key mechanism identified in metastatic breast cancer
Date:5/4/2010

Scientists at the University of Kentucky Markey Cancer Center have identified a key molecular mechanism in breast cancer that enables tumor cells to spread to adjacent or distant parts of the body in a process called metastasis. This finding opens the way to new lines of research aimed at developing treatments for metastatic breast cancer.

The research, led by Peter Zhou, associate professor of molecular and cellular biochemistry at UK, focused on the process by which tumor cells stop clinging to other cells and become motile, or able to spread throughout the body. The findings were published in an article in the EMBO Journal, the flagship publication of the European Molecular Biology Organization.

The increased motility of tumor cells at the initial step of metastasis is similar to a process called epithelial-mesenchymal transition (EMT), which is required for large-scale cell movement in embryonic development, tissue remodeling and wound healing. For example, during wound healing, cells at the edge of the wound undergo a EMT process and migrate to the middle for sealing the wound.

In all EMT processes, cells lose the expression of a cell-to-cell adhesion molecule called E-cadherin, which functions as a "molecular glue" that attaches cells to one another. Breast cancer cells usurp this process for invasion and metastasis. When this molecular glue is broken down, tumor cells start to migrate and spread throughout the body.

A protein called Snail acts as a master switch in the cell's nucleus to suppress E-cadherin expression and induce EMT in the cell. Previous research has shown Snail to be elevated in many types of cancer, particularly breast cancer. High levels of Snail have been linked to metastasis, tumor cell survival and tumor recurrence, and thus predict a poor clinical outcome for women with breast cancer. However, scientists are still not clear how Snail triggers the down-regulation of E-cadherin and induces m
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Contact: Keith Hautala
klhaut2@uky.edu
859-257-1754
University of Kentucky
Source:Eurekalert

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