New research by Cardiff scientists with colleagues at King’s College London has identified the switch which releases zinc into cells, with important implications for a number of diseases.
Zinc has long been known to play a vital part in human health. Too much zinc, or too little, can cause cell death. A growing body of evidence links zinc to disease states including neurodegeneration, inflammation, diabetes and cancer.
Zinc levels in cells are controlled by protein molecules called zinc transporters. These move zinc in and out of the cell to ensure correct levels are maintained. Until now, scientists have not understood how the transporters release the zinc. The new study, including Dr Kathryn Taylor at the Cardiff School of Pharmacy and Pharmaceutical Sciences, and Dr Peter Kille at the School of Biosciences, has identified a switch known as CK2. This is a protein which opens one transporter, called ZIP7, and allows the zinc to flow.
Earlier research by the team has already linked zinc delivery to types of breast cancer. Higher levels of intracellular zinc and the ZIP7 transporter were found in tamoxifen-resistant breast cancers. CK2 was also known to be more common in cancers which encourage cell growth. The discovery that CK2 opens ZIP7 suggests that drugs which block this release of zinc could also block cancer development. Early results from clinical trials of CK2 inhibitors suggest they are performing well.
Dr Taylor said: “We know that zinc, in the right quantities, is vital for development, our immune systems and many other aspects of human health. But when something goes wrong with the body’s zinc delivery system, it looks as though disease can result. In particular, our research has shown a link to highly aggressive forms of breast cancer. Our better understanding of how exactly zinc is delivered suggests if we can block malfunctioning transporter channels, we can potentially halt the growth of these forms of cancer. We believe this makes zinc, and zinc delivery, a high priority for future cancer research.”
The research, funded by a Wellcome Trust University Research Award to Dr Taylor, is published in the leading journal Science Signaling.