HOUSTON A protein which is intimately involved in cancer-promoting cell signaling also keeps a key component of the signaling pathway tied down and inactive, a team led by scientists from The University of Texas MD Anderson Cancer Center reports this week in Nature Structural Molecular Biology.
Shc, pronounced "schick," plays a key role in activating signals which lead to cell proliferation (and cancer) when cells are stimulated, however it unexpectedly turns out to be a tumor-suppressor, keeping Erk under wraps when a cell is less active, said senior author John Ladbury, Ph.D., professor in MD Anderson's Department of Biochemistry and Molecular Biology.
"Shc is a checkpoint to prevent out of control cell growth, binding to Erk when a cell is not being stimulated by growth factors," Ladbury said. "Otherwise, the lower-level background signaling that's always present in a cell would be uncontrolled."
Keeping Erk in check while the cell idles
Overexpression of Erk occurs in many types of cancer, including ovarian and prostate cancer and Hodgkin lymphoma, so cellular control of its activity is important.
In the absence of external stimulation by growth factors, cells remain active but lower levels of cell signaling occur, which Ladbury compares to a car idling, ready to roll. Under these conditions control mechanisms are in place to prevent the cell kicking into gear. Shc turns out to be one of these controllers.
"We're essentially looking at the cell in a resting, but ready, state," Ladbury said. "I would argue that's probably more like a cell behaves in tissue, it's not normally getting a slug of growth factors as is often the way when we investigate signaling in experiments in the lab. There's still a lot going on in the cell, basically background activity."
These findings point to a number of therapeutic possibilities, including the measurement of Shc concentration levels as a diagnostic t
|Contact: Scott Merville|
University of Texas M. D. Anderson Cancer Center