A team of University of Pittsburgh researchers has identified a previously unknown "fail-safe" mechanism that helps keep cell division from going awry and thus prevents cells from becoming malignant.

It's yet another piece of the complex mechanism that cells use to duplicate themselves that these researchers have uncovered as they try to find new ways to fight cancer.

"You have to understand the mechanism before you can impact the clinical setting," explained William Saunders, an associate professor of biological sciences, who heads one of the two research teams collaborating in the study.

The latest finding identifies a couple of additional targets for future cancer therapies. But Susanne Gollin, a professor of human genetics in the Pitt Graduate School of Public Health who heads the other research team in the study, cautioned that the cell division mechanism is so complex that additional pieces will need to be identified and targeted as well before the findings can be translated into a possible treatment.

Researchers have known for years that cancer cells often include extra copies of chromosomes, or have missing chromosomes ---- a consequence of mistakes that occur when cells divide.

Normally, before a cell divides, copies are made of each chromosome. As the cell divides, a structure called a spindle works to pull the chromosomes apart so that each of the daughter cells will have an equal number of chromosomes.

At each end of the spindle are proteins called centrosomes, which form "spindle poles" that attach to the chromosomes. But if the cell contains more than two centrosomes, it's possible for additional spindle poles to form, causing the chromosomes to be divided unequally between the daughter cells.

"Extra centrosomes are really, really bad," said Nicholas Quintyne, a post-doctoral fellow in Saunders' lab who conducted most of the new work. But scientists have been puzzled because sometimes even cells with extra centrosomes divide normally.

The reason, Quintyne discovered, has to do with a protein called dynein, which is involved in the formation and maintenance of spindles. Dynein helps hold extra centrosomes together in a single spindle pole, providing a fail-safe mechanism; without it, the centrosomes separate, multiple spindle poles form, and bad things happen.

Excessive levels of another protein, called NuMA, can inhibit dynein, the researchers found, and thus can lead to duplication errors.

Therapies that reduce NuMA levels and promote normal dynein function thus might help fight cancers. But the researchers emphasize that NuMA doesn't explain all of the failures of this mechanism and that other proteins that inhibit dynein must be studied before clinical applications are possible.