Enzyme target for cancer, parasites
known cancer-related gene and a cellular enzyme that could be the
target of a new generation of drugs aimed at cancer and parasitic
infections.
The target is an enzyme involved in the production of a molecular 'anchor' called GPI (glycosylphosphatidylinositol) that is used to attach cellular proteins to the surface of the cell. The GPI-anchored proteins are involved in a range of cellular functions, regulating the way cells interact and connect with one another.
Impairments in this system are thought to allow the spread of tumour cells, and GPI-anchored proteins are also the point of attachment for a number of parasites, including the Plasmodium organism that is responsible for hundreds of millions of cases of malaria, and kills more than one million African children annually.
The scientists, from the Johns Hopkins Bloomberg School of Public Health and other institutions, note that the activity of the enzyme is related to mutations in Ras, a protein that is mutated in a number of human cancers,
The discovery may provide a new understanding of how tumour cells become malignant and how parasites defend themselves against the body's immune system, according to the researchers, who have published their findings in the journal Cell (28 May issue).
"Scientists have known for many years that Ras proteins work as molecular 'on/off' switches that can change the way cells grow, and interact with other cells," said David Levin, co-author of the study and a professor in the department of biochemistry and molecular Biology at the Bloomberg School of Public Health.
Mutated forms of Ras that are locked in the 'on' position are involved in about 30 per cent of all human cancers, he added, and the new study identifies a new way in which these forms of Ras may drive tumour progression.
The researchers found that Ras inhibits the enzyme target and interferes with the production of cell surface GPI-anchored proteins. In a Ras-driven cancer cell, such regulation of cell surface proteins may enable individual cells to break away from the primary tumour, a key to the spread of cancer to distant sites.
"If Ras regulates the production of GPI-anchored proteins in cancer cells, drugs can be designed to interfere with that regulation and prevent the cancer from spreading," said Dr Levin.
