Dr Jorg Hartkamp and Dr Stefan Roberts have found that the protease HtrA2 can "clean" cells of the oncogene WT1, which is found at high levels in many leukaemias and solid cancers such as breast and lung cancer.
Their work has given drug designers a new target which will allow them to develop treatments for all these cancers in which WT1 expression is elevated.
WT1 is a well-known factor in cancer, having been discovered 20 years ago. It suppresses the development of Wilms' tumour of the kidney, a rare cancer that affects one in 10,000 children. However it has a cancer causing role in other forms of the disease, particularly leukemias such as acute myeloid leukaemia (AML) and chronic myeloid leukaemia (CML).
In addition high expression of WT1 is associated with a bad prognosis in AML patients, while trials using peptide vaccines against WT1 in patients with lung cancer, breast cancer and leukaemia were promising.
This latest study published in the journal Molecular Cell and funded by the Wellcome Trust, Cancer Research UK and the Association of International Cancer Research (AICR) is the first to identify the enzyme that can rid cells of WT1.
Dr Hartkamp, at the University of Manchester's Faculty of Life Sciences, said: "The cancer causing role of WT1 has been known for many years, but how it worked was not understood so we studied a regulatory domain of WT1 to see what modified its activity. We carried out a fishing experiment and discovered the role of the protease HtrA2 instead, by accident. This discovery has a much bigger impact.
"We have filled in the black box of WT1. It is this protease that is doing the trick it can clean cells of WT1."
Dr Roberts, who initiated the work at Manchester and is now at the University at Buffalo, added: "There are great prognostic implications in leukaemias but this protease may have even more targets. It is unlikely that a protease cleaves only one t
|Contact: Mikaela Sitford|
University of Manchester