It's relatively easy to run studies that explore the association between gene expression and cancer prognosis. Those studies, however, don't always paint a clear picture of what the genes do—many of them may be effect (instead of cause) or simply innocent bystanders that are simply caught up in the changes caused by cancer progression. A new study that appears in today's issue of Nature not only describes a strong correlation between the expression of a gene and the ability of breast cancer cells to metastasize, but also presents evidence that indicates the gene plays a key role in regulating the process.
The researchers started with 24 breast cancer cell lines and found that one gene, SATB1, was expressed in all of them. That link held up in cells taken directly from breast cancers, and, in a large population study with tissue from 1,000 patients, SATB1 showed a very significant correlation with longer survival times.
The authors then switched from correlation to experimental evidence. Invasive cancer cells were made to express interfering RNAs that blocked SATB1 expression. The loss of SATB1 had a variety of effects, including reducing the cells' proliferation and inducing them to form duct-like structures that normally appear in the breast. The cells themselves went from a spiky shape that sent out many invasive processes to one that was relatively rounded and, by one measure, was 85 percent less invasive. The researchers also injected cancer cells, with and without the SATB1 RNAi, into immunocompromised mice. The ability to invade and form tumors correlated with the cells' expression of the gene. The same held when a complementary experiment was done: cells that normally fail to establish themselves in mice became tumor forming when engineered to express SATB1.
