Possible drug target to stop breast cancer metastasis identified

London, Jan ary 28: UC San Francisco researchers have found the spread of breast cancer to distant organs within the body, an event that often leads to death, appears in many cases to involve the loss of a key protein.

Their finding points to possible targets for therapy.

UCSF scientists describe for the first time how the protein, known as GATA3 – which is abnormal or absent in many cases of human breast cancer – normally acts downstream in biochemical pathways to prevent the distant spread of cancer, an event called metastasis.

The discovery points to a biochemical control point that simultaneously holds in check several key events required for tumor cells to successfully spread.

“When GATA3 is present, it turns off many genes that are active in metastasis. We now have identified the molecular mechanisms involved,” said Zena Werb, PhD, a UCSF professor of anatomy who led the research.

The key finding of the new study is that GATA3 acts downstream biochemically to activate a molecule – obscure until now – called microRNA29b. MicroRNA29b in turn stops protein production from other genes that play vital roles in metastasis.

The absence or loss of GATA3 can free cancerous cells to break free from their defined roles and tethers within a tumor, to move away from the tumor mass, to induce cancer-promoting inflammation, and to stimulate the development of new blood vessels that can help spreading cancerous cells regrow as tumors in new locations.

Working with mice, the researchers found that restoring microRNA29b to one of the most deadly types of breast cancer stopped metastasis. But the researchers also found that if they knocked out the microRNA29b, tumors spread even in the presence of GATA3, suggesting that microRNA29b can be the driver of metastasis.

In the mouse models of breast cancer studied by Werb’s team, GATA3 normally restrains cancerous cells from breaking away from the main tumor and migrating to other organs.

It might be possible, Werb said, to develop drugs that inhibit breast cancer metastasis by re-activating these controls in cancerous cells that have lost the normal protein.

The study recently appeared in online edition of Nature Cell Biology. (ANI)