In a study published in Nature Chemistry, researchers have revealed how a molecule that was first discovered in bacteria, blocks a protein which causes breast cancer to develop and spread. Investigators at Cancer Research UK’s Cambridge Research Institute, funded by the Biotechnology and Biological Sciences Research Council (BBSRC) and The University of Cambridge, have shown at the molecular level how thiostrepton (a naturally-occurring cancer-protector molecule) “clamps” a cancer-causing protein called FOXM1, preventing it from working.
FOXM1 is present in larger amounts in breast cancer cells, and attaches to specific stretches of DNA – switching on genes regulating the growth and division of cells. FOXM1 also causes tumors to spread and initiates the growth of blood vessels which provide tumors with nutrients for growth.
The development of cancer at a primary stage may be prevented by blocking this protein, in addition to blocking cancer growth and spread.
For researchers designing drugs to stop proteins like FOXM1 is a massive challenge. However, this new data will permit investigators to design small molecules that mimic thiostrepton, but are even more efficient at blocking the cancer-promoting effects of FOXM1.
Based at Cancer Research UK’s Cambridge Research Institute, lead author, Professor Shankar Balasubramanian explained,
“Before this research we weren’t aware of any natural product which could directly target a protein that controls gene activity. Yet intriguingly a molecule in bacteria – which also has strong antibiotic effects – does this very well, switching off cancer-causing genes in breast cancer cells.
This naturally-occurring molecule doesn’t have all the right properties to be used as a breast cancer treatment itself. But this exciting discovery paves the way for the design of more potent and selective drugs based on the structure of thiostrepton to block the FOXM1 protein.”
In the UK approximately 48,000 women are diagnosed with breast cancer every year and around 12,100 die from the disease.
Dr Lesley Walker, Cancer Research UK’s director of cancer information, says,
“Survival rates for breast cancer have been improving for 30 years thanks to the development of more targeted treatments. But there is more to be done. One huge challenge is how to prevent breast cancer from spreading to other parts of the body – once a cancer has spread it becomes more difficult to treat successfully.
It’s fascinating to discover how a simple bacteria could hold the key to powerful new approaches to treat breast cancer developing and spreading.”
Written by Grace Rattue