According to Professor Rob Richards, Head of Genetics and Evolution in the University’s School of Biological Sciences, “We’ve known for some time that in certain types of cancer, people with low levels of WWOX protein are more likely to develop cancer. We also know that cancers with low levels of WWOX tend to be more aggressive and less responsive to treatment. A higher level of WWOX activity is definitely a good thing to have, but, until now, the role that WWOX plays in cancer suppression has been a mystery.”
Working with his team of researchers, Dr Louise O’Keefe and Ph.D. students Amanda Choo and Cheng Shoou Lee, Professor Richards studied the impact of lower levels of WWOX on cells using a genetic model: the small laboratory fly, Drosophila. As Professor Richards explained, “Our research has shown that cancer cells with lower levels of WWOX had a competitive advantage over those cells with normal WWOX levels, and could outgrow them. This could lead to a more aggressive cancer and worse outcomes for cancer patients: poorer survival rates.”
After additional research, the scientists saw that the WWOX gene plays a role in the altered metabolism of cancer cells that are known to use glucose differently from normal cells. Cancer cells are likely to use glucose to create more cell building blocks than energy, and this process is what is assumed to help them to divide and grow.
Professor Richards added, “Another set of Drosophila experiments revealed that the WWOX gene helps keep the balance of glucose use in favour of producing energy rather than helping cancer cells multiply. This difference in metabolism is a key part of how cancer cells have a competitive advantage over normal cells. Low WWOX levels will allow more glucose to be used for these cancer cell building blocks.”
The research offered good news: is that WWOX belongs to a family of proteins that have enzyme activity. Thus, WWOX activity can be altered by targeting the enzyme.
“We now have a good idea of what WWOX does in cancer cells and how it acts to help suppress cancer. And we have a potential target to be able to influence that activity to change the properties of cancer cells,” Professor Richards concluded.