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Researchers reveal aggressive breast cancer's metastatic path
Date:1/14/2013

reast cancer subtypes because of its high recurrence rate and metastatic spread. This is why the research team chose to examine the role of miRNAs in the spread of triple negative breast cancer, which accounts for 15-25 percent of all breast tumors. The cancer is named "triple negative" because its tumor cells do not display two hormone receptors (estrogen and progesterone) or HER2/neu growth factor, which each form the basis of current targeted breast cancer treatments.

Using genome wide miRNA sequencing, Dr. Mittal and his research team found in human samples of triple negative breast cancer that miR-708 was significantly down-regulated with its normal expression curtailed. In both laboratory cells and in animal studies, the researchers identified that the normal role of miR-708 is to suppress the protein neuronatin, which is located on the membrane of a cell's endoplasmic reticulum -- an organelle that stores calcium. Neuronatin helps control how much calcium leaves that organelle.

"It is calcium that provides legs to cancer cells to help them escape a tumor. So miR-708 acts as a suppressor of metastasis by keeping neuronatin in check," Dr. Mittal says. "If miR-708 is itself suppressed, there is an increase in production of neuronatin proteins, which then allows more calcium to leave the endoplasmic reticulum and activate a cascade of genes that turn on migratory pathways leading to metastasis."

Researchers found that delivering synthetic miR-708, carried by bubbles of fat, blocked metastatic outgrowth of triple negative breast cancer cells in the lung of mice. This makes miR-708 a promising therapeutic against metastatic breast cancer. The researchers also discovered that polycomb repressor complex proteins are responsible for silencing miR-708. These proteins remodel the way DNA is packaged in order to epigenetically silence genes.

Dr. Mittal adds that the findings suggest that pharmacological agents now being tested in ly
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Contact: Lauren Woods
Law2014@med.cornell.edu
646-317-7401
Weill Cornell Medical College
Source:Eurekalert

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