Protein that can stop breast cancer from spreading found
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Researchers from University of California - San Francisco found that the spread of breast cancer to distant organs within the body appears in many cases to involve the loss of a key protein.
The protein, known as GATA3 normally acts downstream in biochemical pathways to prevent metastasis, the distant spread of cancer.
The discovery points to a biochemical control point that simultaneously holds in check several key events required for tumour 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 lead researcher Zena Werb.
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 tumour, to move away from the tumour mass, to induce cancer-promoting inflammation, and to stimulate the development of new blood vessels that can help spreading cancerous cells regrow as tumours in new locations.
"People knew that some of these genes were turned on in some cancers, but they did not know they were turned on because GATA3 and microRNA29b were turned off," Werb said.
"If you have 20 genes that are becoming less active all at once due to microRNA29b, it could have a profound effect," Werb said in a statement.
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, tumours spread even in the presence of GATA3.
In the mouse models of breast cancer studied by Werb's team, GATA3 normally restrains cancerous cells from breaking away from the main tumour 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 targeting we would like to do is to give back microRNA29b specifically to breast tumour cells to prevent metastasis," Werb said.
The study was published in journal Nature Cell Biology.