New Target Protein Identified in Cancerous Cells

Investigators have identified an enzyme that is the target of the Ras oncoprotein. The finding, reported in the May 28, 2004, issue of Cell, may provide new insights that would aid the development of new treatments for parasitic infections and cancers.

The enzyme produces a molecular anchor that allows specific proteins to adhere to the cell surface. These molecules, known as glycosylphosphatidylinositol- (GPI)-anchored proteins, regulate the way cells interact and connect with one another. GPI-anchored proteins are also used by parasites, such as the Plasmodium bacterium that causes malaria, to defend themselves again the body's immune system.

"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. Mutated forms of Ras that are locked on the ‘on' position are involved in about 30% of all human cancers,” said David Levin, Ph.D., coauthor of the study and a professor in the department of biochemistry and molecular biology at the Johns Hopkins University Bloomberg School of Public Health (Baltimore, MD, USA).

Dr. Levine and coworkers studied Ras interaction with an enzyme needed for the synthesis of GPI-anchors in yeast cells. They discovered that yeast Ras inhibited the enzyme, thus interfering with the production of cell surface GPI-anchored proteins. In a Ras-controlled cancer cell, this regulation of cell surface proteins may enable individual cells to break away from the primary tumor, a key to the metastasis process. Dr. Levin also said that parasites produce GPI-anchored cell surface proteins as a way to defend against the host's antibodies. Further study is planned to determine if production of GPI-anchored proteins is correspondingly controlled in parasite and animal cells.

"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.




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