Published online 12 March 2008 | Nature | doi:10.1038/news.2008.667

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A protein that makes breast cancer spread

Researchers pinpoint protein 'boss' that controls gene expression.

Will it spread? One protein controls the expression of many genes that dictate whether breast cancer will metastasize.Getty

A protein that determines whether breast cancer will spread and become deadly has been found. Researchers say that the protein, which is found inside the nuclei of cells, would be difficult and potentially dangerous to target with drugs. But monitoring for the protein could help patients to know how dangerous their cancer is before it spreads elsewhere, and help them to decide which treatment to chose.

Because breasts are not critical to survival, cancers that remain within breast tissue do not kill the patient. But if the cancer cells break away from the original tumour, settle and start dividing elsewhere, these secondary tumours can threaten the function of vital organs.

Rather like an invasive plant landing on an island, the circulating breast cancer cell needs to evolve genetic changes to survive in a new environment. It has to find a way to stick to a new type of cell or supporting structure, called a matrix, and form links to surrounding cells, for instance.

Now a protein has been found that changes the levels at which more than a thousand genes are expressed in breast cancer cells, seemingly controlling whether cancer cells will survive elsewhere. The protein is called SATB1. “All sorts of molecular pathways that enable the cell to invade and inhabit a new microenvironment are under the control of SATB1,” says Terumi Kohwi-Shigematsu of the University of California, Berkeley, who was an author of the study.

The nuclear organizer

Kohwi-Shigematsu and her colleagues had previously shown that SATB1 acts as an architect inside the nuclei of cells, directing loops of DNA to clump together. By changing the spatial arrangement of DNA, SATB1 can alter the proteins surrounding some sections of the genome, and in changing this 'casing' effectively turn some genes on and others off.

When the researchers looked for SATB1 in breast cancer cells from more than 1,300 samples, they found a striking pattern. In almost all cases, the more SATB1 those cells contained, the more aggressive the tumour was.

At present, the test to see whether a cancer can spread to other organs, or metastasize, involves looking for the cancer in the lymph nodes. But this catches a tumour only in the act of spreading, rather than beforehand. Crucially, in this study the link between high levels of SATB1 and aggressive tumours held for breast cancers that had not yet spread to the lymph nodes.

This means that the protein could be a good prognostic test for women with breast cancer. “If we discover that this protein is present in the primary tumour, we will have a good idea that the prognosis of this woman will be different and maybe that will lead to a different choice of treatment,” says co-author Jose Russo from the Fox Chase Cancer Center in Philadelphia, Pennsylvania. Patients with more aggressive tumours may chose to be more precautionary and have a larger section of their breast removed, for example.

Growth control

To show that SATB1 was both necessary and sufficient for breast cancer metastasis, the team used a technique called RNA interference to remove it from highly aggressive cancer cells in mice. This inhibited tumour growth. They then added SATB1 to non-aggressive breast cancer cells in mice. This caused those cells to alter the combinations of genes they expressed, and made the cells resemble metastatic cells. The study is published in the journal Nature1.

“Researchers have been describing changes to the DNA casing of large groups of genes in cancer cells, but they have not understood what causes those changes,” says Frances Shannon, a researcher at the Australian National University in Canberra. “This study goes a step further by identifying what causes those changes," she says. But, she adds, the next question is "what leads SATB1 levels to rise?". 

  • References

    1. Han, H.-J., Russo, J., Kohwi, Y. & Kohwi-Shigematsu, T. Nature 452, 187-193 (2008). | Article |
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