Study Identifies Key Step Allowing Cells To Migrate

Their work helps explain how cells can stick to a surface long enough to pull themselves and move forward and then release that grip so that they can continue and not be anchored to one spot.

Cai Huang, a graduate student about to complete his doctorate in cell and developmental biology at the UNC School of Medicine, led the project. He and colleagues showed for the first time that an important enzyme known as JNK, which is involved in many cell regulatory pathways, also controls a central and complex step in the biochemical process.

A report on their work appears in the July 10 issue of Nature, the top British science journal. Co-authors are Drs. Ken Jacobson and Michael Schaller, professors of cell and developmental biology; Dr. Zenon Rajfur, research assistant professor of cell and developmental biology; and Dr. Christoph Borchers, assistant professor of biochemistry and biophysics and faculty director of the UNC Proteomics Core Facility.

"Cell migration is involved in a variety of normal and pathological events in life, including embryo development, wound healing and the abnormal, life-threatening movement of cancer cells that doctors call metastasis," Jacobson said. "Cai's work demonstrates how phosphorylation of a single serine residue of an important protein component of cell adhesion, paxillin, can regulate cell migration."

Phosphorylation is a major signal in biology that involves joining a phosphorus group to specific amino acids, one of the ways living things regulate functions of proteins, he said. A serine residue is one of the 20 or so amino acids that are linked together in various combinations to form the many different proteins found in cells.

"For cells to be able to move, they must have adhesions that can break down from time to time," Jacobson said. "If they were permanent--in other words too sticky--the cell would be stuck. The new work shows this phosphorylation event is important in signaling the cell to disassemble some of its adhesions so that it can move."

The experiments were done on both fish scale cells and rat bladder tumor cells. They identify a specific biochemical pathway by which signals from outside cells--provided by hormones and growth factors--can regulate cell locomotion, he said. Understanding the complex cascade of molecular events could become a key to solving the mystery of how to stop cancer cells in their tracks, like nailing shoes to the floor.

"Another significance of this study is beyond cell migration," Huang said. "Previously, JNK was thought to function solely in cell nuclei. Our finding that paxillin, which is called a focal adhesion protein, is a target for the JNK enzyme indicates that JNK also plays an important role in cytoplasm, which is outside the nucleus."

Thus, the experiments greatly expand knowledge of what JNK does, he said.

"We expect to identify more cytoplasmic JNK targets in the near future," Huang said.

Besides cell and developmental biology, the researchers are affiliated with UNC's Comprehensive Center for Inflammatory Disorders, Lineberger Comprehensive Cancer Center and department of biochemistry and biophysics.

Grants from the National Institutes of Health, the Cell Migration Consortium and the National Institute for Dental and Cranial Research supported the studies.