A single protein may trigger the spread of breast cancer cells to other parts of the body by altering the behavior of large numbers of genes. The protein, SATB1, could potentially be used to identify women at risk of metastasis and may be a therapeutic target, Dr. Terumi Kohwi-Shigematsu of the Lawrence Berkeley National Laboratory and her colleagues report in the March 13 Nature.

They describe the protein as a "genome organizer." It coordinates the activity of genes from different chromosome regions by changing how DNA is packaged in the cell nucleus. For cells to acquire new functions, such as invading other tissues, they may need to induce global changes in gene activity.

In breast cancer cells, SATB1 activity may be necessary for and sufficient to induce metastasis. Blocking the protein in an aggressive breast cancer cell line altered the activity of more than a thousand genes and caused the cells to stop tumor growth and metastasis. Conversely, expressing the protein in a non-aggressive cell line fueled growth and metastasis.

The researchers say that SATB1 activity in breast cancer cells could identify women with early-stage disease who are at risk of metastasis. The primary prognostic indicator of metastasis has been the involvement of the lymph nodes, but additional markers are needed.

"Once this protein is expressed in breast cancer cells there is a very high propensity for metastasis," said Dr. Kohwi-Shigematsu. "And it may be possible to predict poor prognosis based on SATB1 expression independently from lymph node status."

SATB1 activity has also been found in colon and lung tumors, and the researchers are investigating how the protein is activated.

In a step toward therapies, the researchers are investigating ways to deliver SATB1 inhibitors directly into breast cancer cells. This is necessary to avoid disrupting the protein's critical role in the development of certain immune cells.