Jagged2 Binding Drives Metastasis in Lung Cancer Study

Researchers have discovered a new, key component in the spread of lung cancer as well as a likely way to block it with drugs now in clinical trial. The study was published on March 14, 2011, in the Journal of Clinical Investigation. A team led by scientists at The University of Texas MD Anderson Cancer Center found a way to identify metastasis-prone lung cancer cells and then uncovered a mechanism that shifts primary tumor cells into a more deadly type of cell with the capacity to move elsewhere in the body. "We think tumors have to learn how to metastasize because they can't do it initially," said paper senior author Dr. Jonathan Kurie, professor in MD Anderson's Department of Thoracic/Head and Neck Medical Oncology. "Cells change in response to cues from their external environment." About 90 percent of all cancer deaths are caused by metastasis - the spread to, and invasion of, other organs. Lung cancer is the leading cause of cancer-related death in the United States, accounting for more than 157,000 deaths annually. The median five-year survival rate is 3.5%. The researchers found that when a protein called Jagged2 binds externally to Notch, a membrane protein that sticks out through the surface of a cell, it suppresses a microRNA that thwarts metastasis inside the cell. "Jagged2 suppresses miR-200 and drives metastasis as a consequence." Dr. Kurie said. "It's been known for some time that Notch is involved in cancer, but no one really knew how." Two Notch inhibitors are in clinical trial at MD Anderson. "These drugs might suppress the ability of primary tumors to metastasize," Dr. Kurie said. "One question is who is supposed to get these drugs," Dr. Kurie said.
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