Scientists Define New Role for Cell Signaling Pathway

Scientists at Norris Comprehensive Cancer Center of the University of Southern California (USC) have found a new fork in a much-studied genetic pathway, and their work may lead to new cancer therapies, according to the center’s director.

The genetic pathway known as the ras pathway already figures large in the control of cell division and growth. In the January 23, 1998, issue of Science, USC researchers confirm a new role for ras—the control of cell shape and movement. The study elucidates the molecular mechanism by which the ras oncogene regulates this process. Their work also sheds light on a mechanism by which more than a hundred related enzymes may be turned on and off in the cell.

Another Fork in the Signal Transduction Pathway

Before any cell divides—whether it be a cell of the skin, the immune system, or a tumor—a cascade of biochemical events occurs inside that cell. The cascade, called a signal transduction pathway, is triggered when a small growth factor binds to a receptor on the cell membrane. The pathway results in a message reaching the cell nucleus telling it to grow and divide. The signal tranduction pathway is a kind of biological domino effect, in which the ras gene and gene products are key dominos. Since this pathway’s errant ways can lead to cancer, scientists have hotly pursued its twists and turns.

Now, USC researchers have defined another fork in the path. A team led by Daniel Broek,PhD, a researcher at the USC/Norris and associate professor of biochemistry and molecular biology at the USC School of Medicine, and Jaewon Han, a USC biochemistry and molecular biology doctoral student, provide the “molecular explanation of how ras can activate rac—an enzyme that directs cellular architecture and motility,” Broek says.

“In terms of human cancer, any molecular defect in this ras to rac pathway is clearly of great importance,” says Peter Jones, PhD, director of the USC/Norris Cancer Center. “Understanding more about the pathway gives us clues to potential therapies that could block incorrect signaling events in cancer cells.”