Two Arms Are Better than One

 

Prof. Yosef Yarden of the Biological Regulation Department led a team of scientists from the Weizmann Institute and the Chaim Sheba Medical Center, as well as Portugal and the U.S., in deciphering a crucial mechanism that controls the first stage of breast cancer metastasis, when the cancer cell first starts to move. This action begins with a signal that comes from outside the cell telling it to prepare for the journey. The signal, called a growth factor, initiates a series of changes in the cell: The cell's internal skeleton comes apart, and the densely packed protein fibers that make up the skeleton unravel to form thin threads that push the cell away from its surroundings.

 

Yarden, Drs. Menachem Katz, Ido Amit and Ami Citri of the Biological Regulation Department; Tal Shay, a student in the group of Prof. Eytan Domany of the Physics of Complex Systems Department; Prof. Gideon Rechavi of the Sheba Medical Center at Tel Hashomer and others set about investigating the protein changes that growth factor signals bring about. They mapped all of the changes in gene expression that take place once the signal is received.

 

As they sifted through huge quantities of data, including every protein level that went up or down, the team noticed one family of proteins that stood out. To the scientists' surprise, one member of this family rose dramatically, while another closely related protein dropped off.

 

Tensins, as these proteins are called, stabilize the cell's internal skeleton. When the team investigated the two proteins, they discovered a significant difference: One of the proteins has two arms, while the other has only one. The two-armed protein – whose level drops in response to the growth factor – stabilizes the cell's structure by grabbing the internal skeleton with one arm and the cell membrane with the other. The one-armed version, in contrast, attaches only to the cell membrane, leaving the protein fibers that make up the skeleton dangling. These unanchored fibers loosen to form the threads that push cells apart. For a cancer cell, this can be the beginning of metastasis.

 

Further experiments were conducted, both on genetically engineered cells and on tissue samples taken from patients with inflammatory breast cancer (a swift and deadly cancer associated with elevated growth factor activity), as well as on samples from cancer patients who had received a drug that blocks growth factor receptors on cell walls. These studies confirmed the ties between the growth factor signal, the levels of the two proteins, and their direct involvement in metastasis.