January 17, 1997

VUMC investigator seeks to translate language of cells.

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Dr. John Exton

VUMC investigator seeks to translate language of cells.

The human body's cells contain millions of molecules that perform a mind-boggling array of functions.

Accomplishing these functions requires cells to, in essence, talk to each other. Both the organization and the metabolic processes of cells are controlled by information that a cell receives from other cells. Dr. John H. Exton, professor of Molecular Physiology and Biophysics and Pharmacology, investigates the process by which cells communicate with each other to fulfill their functions.

"Information which passes between the cells as hormones in the blood stream, neurotransmitters, and related compounds are involved with cell growth and just about every other function," said Exton. "My research is currently most closely linked to cancer research because cancer cells are basically cells that are out of control."

Cancer arises from the uncontrolled and abnormal division of cells that then invade and destroy surrounding tissues. Key to any discovery of how to stop this process is discovering how these cells communicate.

Exton is currently involved in studying the role of an enzyme, Phospholipase D, in living systems. The enzyme is seemingly everywhere in the human body and yet no one knows exactly what it does.

"Phospholipase D's activity is turned on by hormones, neurotransmitters and growth factors in mammalian systems," said Exton. "It has to be important because nature does not waste effort on enzymes that do not perform a useful function."

In a recent paper that has received a substantially greater number of citations than other papers of its genre, according to the Science Citation Index of the Institute for Scientific Information, Exton revealed that a link exists between the enzyme Phospholipase D and an important cellular protein, RhoA.

Signals from the RhoA protein can lead to changes in a cell's growth, adhesion, and protein secretion and is important in a cell's transformation into a cancer cell.

"We brought that protein RhoA together with Phospholipase D and showed that it was activated in rat liver. Since then, we've found that the enzyme is regulated by RhoA in the brain, liver, spleen ‹ many other tissues," said Exton.

RhoA and related proteins have many effects on cells. One of these is to alter a cell's cytoskeleton, which changes the appearance and motility of a cell.

"If all the filaments line up in the cell together, the cell can become elongated or they can line up against the membrane," said Exton. "The resulting changes in cell shape and movement may be very important in cancer."

If Exton establishes a link between cancer cell metastasis, or the distant spread of cancer from its site of origin, and RhoA and Phospholipase D, then it may prove possible someday to manipulate that link to perhaps halt the unchecked spread of cancer cells.