Cambridge scientists discover abnormal cell death mechanism works 'under normal conditions'

In collaboration with Adfero

UK scientists studying how cells die have discovered that 'abnormal' death mechanism actually seems to occur in normal breast tissue.

The mechanism - involving parts of the cell known as the lysosomes - was observed in breast cells in mice by scientists at the University of Cambridge's Department of Pathology.

The discovery, which is published in the journal Nature Cell Biology, opens up new avenues of research into how tumour cells evade treatment, and may ultimately provide new targets for the development of anti-cancer therapies.

The researchers found that cells in the breast die after lactation by a process that differs from the usual mechanism of cell death (apoptosis), in which cell changes and death are brought about through a series of biochemical events.

Studies on mice revealed that breast cells die by a process that involves lysosomes - structures inside cells that digest and recycle cellular components.

During the process, enzymes called cathepsins leak out of the lysosomes and cause the cell to die.

The researchers also discovered that this new process of cell death involves a protein called Stat3, which has previously been shown to be present in higher levels in aggressive cancers.

Stat3 appears to promote high levels of cathepsins - the enzymes that cause cell death - and suppress cathepsin inhibitors.

Peter Kreuzaler, who made the discovery during the course of his PhD research, revealed: "Our work is the first to show that a lysosomal pathway of cell death occurs in a normal situation in the body.

"Current cancer research focuses on understanding how cancers evade cell death. The discovery of a novel pathway of cell death is likely to explain a yet unexplained tumour resistance to cell death, while giving researchers new prospective therapeutic targets."

Henry Scowcroft, science information manager at Cancer Research UK, said: "This is fascinating research, showing that a new cell death pathway is present in the breast cells of mice. If the same is true in people, then this could open up a new avenue of research into breast cancer.

"What's particularly interesting is that the protein that seems to control this pathway also appears to be involved in aggressive breast cancers, which are harder to treat. It will be interesting to see how this research pans out over the coming years."

References

  • Kreuzaler, P., Staniszewska, A., Li, W., Omidvar, N., Kedjouar, B., Turkson, J., Poli, V., Flavell, R., Clarkson, R., & Watson, C. (2011). Stat3 controls lysosomal-mediated cell death in vivo Nature Cell Biology DOI: 10.1038/ncb2171