Identification of Key Mechanism in Breast Cancer

A key molecular mechanism that favors spreading of tumor cells to adjacent or distant regions of the body has been identified by researchers at the University of Kentucky Markey Cancer Center. This process is called metastasis and appears in breast cancer as well as in other types of this disease. As a result of this study, ways to new lines of research are opening, which aim at developing efficient treatments for metastatic breast cancer.
The team led by Peter Zhou, associate professor of molecular and cellular biochemistry at UK, concentrated on studying the process by which cancer cells stop holding tight to other cells and become capable to move and spread throughout the entire body. The results of the research were published in the EMBO Journal, the most representative publication of the European Molecular Biology Organization.
The motility of tumor cells is increased at the initial phase of metastasis and is similar to the epithelial-mesenchymal transition process (EMT) that is necessary for large-scale movement present in embryonic development, wound healing and tissue remodeling. It is known that during wound healing cells from the edge of the wound are subject to an EMT process and migrate to the middle of the wound in a sealing effect.
All EMT processes are characterized by loss of a cell-to-cell adhesion molecule called E-cadherin, which has the role of molecular glue. It attaches cells to each other. Breast cancer cells take control of this process and proceed to invasion and metastasis. When this molecular glue is destroyed, cancer cells start to migrate and then spread throughout the whole body.
Snail is a protein that acts in the cell’s nucleus, suppresses E-cadherin expression and induces EMT in the cell. As previous researches have shown, Snail is elevated in many forms of cancer, and particularly in breast cancer. Increased levels of Snail have been related to metastasis and tumor cell survival, as well as tumor recurrence. Scientists are not yet sure how Snail manages to trigger down-regulation of E-cadherin and induce metastasis in breast cancer.
Zhou and his team used a protein purification approach and found that Snail makes team with the LSD1 enzyme, inside the cell. LSD1 is already known to produce changes in the structure of DNA and inhibits the expression of many genes.
LSD1 is not chemically related to the hallucinogen LSD and stands for lysine-specific demethylase-1. It regulates the chromosome’s structure by removing a key methylation at histone H3, which is a core component warping the DNA into compact form. Thus, the closure of DNA is started and down gene expression, such as E-cadherin, is shut. According to Zhou’s team, the N-terminal portion of Snail molecules works as a molecular hook for recruiting LSD1 to the E-cadherin gene. This one, in turn, will shut down the expression of E-cadherin and will induce cancer cell invasion and metastasis.
This research has important clinical implications, as chemical agents or compounds that are able to break the interaction of Snail with LSD1 have great potential in metastatic breast cancer treatment. Scientists are exploring this idea and are committed to develop medication efficient in metastatic cancer treatment.
One of the most common forms of cancer in women, breast cancer determines an important rate of mortality. About 90 percent of death cases are caused by local invasion and distant metastasis. The average survival after the appearance of metastasis is about two years.
According to Peter Zhou, a good understanding of the mechanism of breast cancer metastasis will allow new therapeutic approaches and will make more efficient the combat against this terrible threat.