Researchers at Tulane University School of Medicine have discovered that if animal cells gain an extra set of chromosomes, a condition known as polyploidy, they activate a stress signaling pathway that causes them to become more mobile and capable of engulfing neighboring cells with normal chromosome numbers. The study, to be published April 21 in the Journal of Cell Biology ( JCB ), could provide new ways to target polyploid cancer cells, which are thought to promote tumor aggressiveness and therapy resistance.
Animal cells are usually diploid: they contain two sets of chromosomes with one set inherited from their mother and one set from their father. Sometimes, however, cells may acquire extra sets of chromosomes and become polyploid. For example, they may duplicate their chromosomes in preparation for cell division but then fail to divide. The extra chromosomes can supercharge the cells, allowing them to resist stress and increase tissue size. This can be a normal, even essential, part of development: many liver cells, for example, have four or more sets of chromosomes. But in tumors, polyploid cancer cells can drive tumor growth, survival, and resistance to therapy.
In the new JCB study, Professor Wu-Min Deng and colleagues at Tulane University School of Medicine investigated how polyploidy affects the behavior of cells that usually remain diploid. The researchers induced the formation of polyploid cells in fruit flies, and found that the cells became more dynamic and mobile, migrating through tissues instead of remaining in place. The polyploid cells also gained the ability to engulf neighboring diploid cells, particularly if those cells were unhealthy and dying. In tumors, these behaviors can help cancer cells spread to surrounding tissue and organs, as well as ensuring that the strongest, most aggressive cancer cells survive at the expense of weaker, less aggressive cancer cells.
Deng and colleagues found that the extra chromosomes make polyploid cells produce more proteins. This overloads part of the cells’ protein production machinery, leading to the production of oxidant molecules that activate a cellular stress pathway involving an enzyme called JNK. Treating flies with antioxidants or inhibiting the JNK pathway reduced the ability of polyploid cells to migrate through tissues.
To investigate whether the same pathway occurs in human cancers, Deng and colleagues induced polyploidy in human lung cancer cells. Polyploid cancer cells became more mobile, but this enhanced motility was blocked by antioxidants or JNK inhibitors.
“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.”
Zhou et al., 2026. <em> J. Cell Biol. </em> https://rupress.org/jcb/article-lookup/doi/10.1083/jcb.202507096?PR
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Journal of Cell Biology ( JCB ) publishes peer-reviewed research in any area of basic cell biology as well as applied cellular advances in fields such as immunology, neurobiology, metabolism, microbiology, developmental biology, and plant biology. All editorial decisions on research manuscripts are made through collaborative consultation between professional editors with scientific training and academic editors who are active in the field. Established in 1955, JCB is published by Rockefeller University Press, a department of The Rockefeller University in New York. For more information, visit jcb.org .
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Journal of Cell Biology
Experimental study
Animals
Polyploidy reprograms epithelial cells for motility and phagocytosis via stress signaling
21-Apr-2026