London, May 05: In a major breakthrough, scientists claim to have identified a key molecular mechanism in breast cancer that enables tumour cells to spread to either adjacent or distant parts of the body through metastasis.
An international team, led by Prof Peter Zhou of the University of Kentucky, has achieved the breakthrough which it says will pave the way to new lines of research aimed at developing treatments for metastatic breast cancer.
The research focused on the process by which tumour cells stop clinging to other cells and become motile, or able to spread throughout body, the ‘European Molecular Biology Organisation’ journal reported.
The increased motility of tumour cells at the initial step of metastasis is almost similar to epithelial-mesenchymal transition (EMT) required for largescale cell movement in embryonic development, tissue remodelling and wound healing.
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.
hen this molecular glue is broken down tumour 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.
High levels of Snail have been linked to metastasis, tumour cell survival and tumour recurrence, and thus predict a poor clinical outcome for women with breast cancer. But, it’s not clear how Snail triggers the down-regulation of E-cadherin and induces metastasis in breast cancer.
Using a protein purification approach, Zhou and his colleagues found that Snail interacts and teams up with its “partner in crime”, an enzyme called LSD1, inside the cell.
LSD1, which stands for lysine-specific demethylase-1, is known to change the structure of DNA and even shut down the expression of many genes. This event triggers the “closure” of DNA structure and shuts down gene expression.
The team showed that the N-terminal portion of Snail molecular functions as a “molecular hook” for recruiting LSD1 to the E-cadherin gene, which, in turn, shuts down expression of E-cadherin and induces tumour cell invasion and metastasis.
“This finding has significant clinical ramification, because chemical compounds or agents that can disrupt the interaction of Snail with LSD1 will have a great therapeutic potential of treating metastatic breast cancer.
“An understanding of the mechanism underlying biology of breast cancer metastasis will provide novel therapeutic approaches to combat this life-threatening disease,” Zhou said.
—-Agencies