January 10, 2006
La Jolla, CA – A research scientist who recently discovered a critical message-relaying pathway that underlies the development of both cancer and type 2 diabetes, in January joined the Salk Institute for Biological Studies as an assistant professor in the institute’s Molecular and Cell Biology Laboratory and Dulbecco Laboratory for Cancer Research.
At the Salk Institute, Reuben Shaw, Ph.D., will follow up on his recent discovery, reported in a December issue of the journal Science, that directly connects tumor suppression to metabolism and diabetes.
Shaw, who comes to Salk from Harvard Medical School in Boston, specializes in the study of one of the tumor suppressor genes. Named LKB1, the gene investigated by Shaw carries the DNA recipe for a protein that is mutated in the rare disorder, Peutz-Jegher Syndrome. People who have inherited a flawed version of the LKB1 gene have a much greater risk (15 times higher than normal) of developing a malignant tumor. The LKB1 gene also is frequently abnormal in people with sporadic lung adenoma, one of the world’s most widespread and lethal cancers.
Reasoning that a therapy that could treat the rarer and easier to study cancer Peutz-Jegher Syndrome tumors could potentially help millions of people afflicted with a much more common form of cancer, Shaw and a group of researchers at Harvard Medical School launched into a deep investigation of LKB1’s function. They found that LBK1 switches on a metabolic enzyme known as AMPK, when levels of energy in a body cell run low.
AMPK has been extensively studied for years, since it is both activated in response to exercise and is triggered by drugs used for treating type 2 diabetes. It acts as a ‘metabolic master switch,’ in two ways. It reduces glucose levels in the blood – with immediate benefits for those with diabetes. Because cancer cells are very active, they usually require more fuel to survive. By depriving tumor cells of the energy they need to grow AMPK puts a damper on the cell proliferation that underlies the growth of cancerous tumors in the body.
This connection between metabolism and cancer via LKB1 may provide a new area of research into the treatment of certain cancers.
Shaw demonstrated that cells lacking a normal copy of the LKB1gene fail to activate AMPK in response to low energy levels in the cell but also, and more strikingly, that tumor cells lacking LKB1 are killed by drugs that normally stimulate this regulatory cascade. These drugs include metformin and glitazones, several of the most widely prescribed type 2 diabetes treatments.
His latest finding, published in December issue of the journal Science, reports that LBK1 not only functions as a tumor suppressor that puts a brake on the cancer process but also hems in glucose production by the liver. In the process, he discovered how metformin, a drug that’s been used to treat type 2 diabetes for nearly 50 years, amplifies insulin’s effect.
On Feb. 15, Shaw will be one of four scientists speaking at a National Cancer Institute seminar for journalists that will be held in San Diego.
“Reuben Shaw is a creative young scientist who has already made major contributions to our understanding of cancer and diabetes. He will bring new ideas, technology, and expertise to the Institute, and we are delighted that he will be joining us,” says Richard Murphy, Ph.D., president and CEO of the Salk Institute.
Shaw, who received his Ph.D. in biology from the Massachusetts Institute of Technology, is one of 58 faculty scientists at the institute, whose basic research identifies the biological principles of life at all levels, from the individual cell, to the whole organism. For more information about the Salk Institute, visit www.salk.edu.