Kill the Messenger

What’s good news for one might spell disaster for another. In cancer for instance, when a certain cell is commanded to grow and divide without restraint, it’s a welcome message for the cell itself but a tragedy for the person who harbors this cell in his or her body. Weizmann Institute scientists have managed to decipher and block one type of molecular message that prompts unbridled cellular growth.

The molecular message first arrives at the cell’s membrane, but its ultimate destination is the cell’s nucleus, which contains the DNA. It’s a huge distance for the message to cross, equivalent to 50 kilometers for a human being. To reach the nucleus quickly, the message is relayed by a chain of chemical messengers, from one molecule to another. More than two decades ago, Prof. Rony Seger of the Weizmann Institute’s Biological Regulation Department took part in the discovery of one such chain – one that participates in the induction of numerous types of cancer; among other molecules, it includes the enzymes MEK1, MEK2, ERK1 and ERK2.

At first, Seger studied the transmission of molecular messages by these enzymes in the cell’s cytoplasm. Only four years ago did he and his team succeed in uncovering the details of the later, most crucial step: the entry of the message into the cell’s nucleus. The scientists identified a segment in the enzymes called NTS. Through the addition of phosphorus molecules, NTS undergoes a change that makes the enzymes’ entry into the nucleus possible. When the researchers created a small peptide mimicking NTS, the message was blocked and failed to reach the nucleus. As a result, the cell stopped growing: Apparently, the peptide had intercepted the “Enter the nucleus!” command. In experiments with mice, the peptide effectively blocked the development of several types of cancer, particularly melanoma: Not only did the tumors stop growing, they disappeared entirely.

Seger’s findings are currently being considered for future biotechnological applications.

 

Prof. Rony Seger's research is supported by the M.D. Moross Institute for Cancer Research; the Willner Family Center for Vascular Biology, which he heads; the Aharon Katzir-Katchalsky Center, which he heads; the Phyllis and Joseph Gurwin Fund for Scientific Advancement; and Katy and Gary Leff, Calabasas, CA. Prof. Seger is the incumbent Yale S. Lewine & Ella Miller Lewine Professorial Chair for Cancer Research.