DISCOVERIES
New Mechanism Proposed for Chromosome Miscounts in Cancer
In the human body, healthy cells divide according to an intricately choreographed sequence of events. When this dance goes awry, disease can take root. Tumor cells, for example, often end up with the wrong number of chromosomes after faulty cell division. A new study from the Dana-Farber Cancer Institute has found an explanation for this phenomenon, debunking a long-held theory about cancer cell division while yielding a path to potential new therapies.
Photo by Graham Ramsay
David Pellman
For more than a century, the prevailing explanation for a cancer cell’s tendency to gain or lose chromosomes was that it was more prone to multipolar division; in this rare process, a cell splits into three or more daughter cells, each one receiving an irregular complement of genetic material. This theory was bolstered by the observation that cancer cells often have extra centrosomes, small structures that organize and tether chromosomes during cell division. Until the recent study, the link between cancer and multipolar division had never been experimentally verified.
Using advanced microscope technology, coauthors Neil Ganem and Susana Godinho, both DFCI postdoctoral fellows, examined thousands of cancer cells from different cell lines. They noticed that contrary to traditional wisdom, multipolar division was too rare and too harmful to the daughter cells to account for the number of chromosomally abnormal cells in a real tumor.
“This paper shows that one way cells become chromosomally unstable is extra centrosomes.” —Neil Ganem |
Instead, the researchers saw a new and unexpected mechanism. Rather than pulling chromosomes in all different directions during mitosis, the centrosomes they observed lined up neatly along an axis, as in a normal cell. But because the cancer cells had too many centrosomes, chromosomes in the middle of the cells were tugged by unequal forces in opposite directions. This explains why the daughter cells had an irregular number of chromosomes, though the researchers noted that other mechanisms could also be at play.
Nevertheless, Ganem said, uncovering this mechanism may lead to new strategies for treating cancer. “This paper shows that one way cells become chromosomally unstable is extra centrosomes. If you take cancer cells and get rid of those extra centrosomes, can you make them less likely to adapt to a tumor, or less likely to evade chemo drugs, or less likely to become metastatic?”
Ganem, Godinho, and David Pellman, the Margaret M. Dyson Professor of Pediatric Oncology at Children’s Hospital Boston and a professor of cell biology at DFCI, reported their results online June 7 in the journal Nature.
Students may contact David Pellman at david_pellman@dfci.harvard.edu for more information.
Conflict Disclosure: The authors declare no conflicts of interest.
Funding Sources: The National Institutes of Health