Extra sets of chromosomes may help aggressive tumor cells spread, study finds

One of the biggest challenges in cancer research is understanding why some tumor cells become especially aggressive, invasive and resistant to treatment. Scientists have increasingly linked these dangerous traits to polyploid cancer cells - cells with extra sets of chromosomes - but exactly how those extra chromosomes help tumors spread has remained unclear.

A new study from Tulane University offers a possible answer. Researchers found that when animal cells gain extra chromosomes, they activate a cellular stress response that makes the cells more mobile and more likely to engulf neighboring cells.

The study, published in the Journal of Cell Biology, used fruit flies and human lung cancer cells to expand the understanding of polyploid cell behavior and points to a possible new treatment strategy for limiting the spread of aggressive, therapy-resistant tumors.

- Youfang Zhou

Researchers found that gaining extra chromosomes prompts polyploid cells to make an abundance of proteins, triggering a stress pathway involving an enzyme called JNK. This stress reprograms the cells, which gain the ability to spread and consume surrounding cells. When researchers inhibited this enzyme in polyploid cells in fruit flies and polyploid human lung cancer cells, each showed a reduced ability to migrate through tissues.

"Our findings have important implications for cancer biology, where polyploid cells are often enriched in aggressive, therapy-resistant tumors," said corresponding author Wu-Min Deng, professor of biochemistry and molecular biology at Tulane University School of Medicine and the Gerald & Flora Jo Mansfield Piltz Endowed Professor in Cancer Research at Tulane Cancer Center. "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."

Most animal cells are diploid, meaning they contain two sets of chromosomes. Polyploid cells are not inherently dangerous. In tissues, such as the heart and liver, where stem cell activity is limited, polyploid cells producing extra proteins can supercharge regeneration and repair damaged tissue.

In tumor cells, however, this behavior has been linked to therapy resistance and aggressive behavior.

"Our study suggests that the same internal stress that helps polyploid cells survive may also make them more mobile and give them a competitive advantage," said co-first author Youfang Zhou, postdoctoral fellow at Tulane University School of Medicine.

In tumors, these behaviors can ensure that the strongest, most aggressive cancer cells survive and spread at the expense of weaker, less aggressive cancer cells.

"Our findings show that induced polyploid cells are not only stress resistant but also actively responsive, engaging in behaviors typically associated with immune or invasive cells," said co-first author Xianfeng Wang, research assistant professor at Tulane School of Medicine.