Study Shows Extra Chromosomes Push Cells to Migrate and Engulf Neighbors

Scientists at Tulane University School of Medicine have identified how animal cells respond when they gain extra sets of chromosomes, a condition known as polyploidy. Their study, published in the Journal of Cell Biology, shows that these cells activate a stress signaling pathway that increases their mobility and allows them to engulf neighboring cells with normal chromosome numbers. These findings point to mechanisms that may contribute to tumor aggressiveness and resistance to therapy.

Under normal conditions, animal cells are diploid, carrying two sets of chromosomes inherited from each parent. In some cases, however, cells replicate their chromosomes but fail to divide, resulting in polyploidy. This state can serve useful biological roles, such as in liver cells that naturally contain multiple chromosome sets. Polyploid cells can better tolerate stress and support tissue growth. In cancer, however, these same properties can promote tumor development, survival, and resistance to treatment.

To explore how polyploidy alters cell behavior, Professor Wu-Min Deng and colleagues induced polyploidy in fruit fly cells that are typically diploid. These cells became more active and mobile, moving through tissues rather than remaining stationary. They also gained the ability to engulf nearby diploid cells, particularly those that were unhealthy or dying. In tumors, this type of behavior could allow more aggressive cancer cells to spread and outcompete less robust cells. 

The researchers determined that the additional chromosomes increase protein production, which places stress on the cell’s protein-processing systems. This stress leads to the accumulation of oxidant molecules that activate a signaling pathway involving the enzyme JNK. When the flies were treated with antioxidants or when the JNK pathway was inhibited, the polyploid cells showed reduced movement, indicating that this stress response drives their enhanced motility.

To assess whether the same mechanism applies in human cancer, the team induced polyploidy in human lung cancer cells. These cells also became more mobile, and this effect was reduced when antioxidants or JNK inhibitors were used, supporting the role of this pathway in promoting movement.

“Our findings have important implications for cancer biology, where polyploid cells are often enriched in aggressive, therapy-resistant tumors,” Deng says. “Our data suggest that elevated reactive oxygen species and JNK activation may underlie the enhanced motility of polyploid cancer cells. Targeting stress-sensing pathways in polyploid cells could therefore represent a new therapeutic strategy to limit tumor invasion.”