Cells need to die, sometimes. The process of cell death is encoded within the genome of all higher organisms to kill off cancerous cells, and as a regular part of the development to shape a mass of embryonic cells into the organism it will become. Researchers at Jefferson have now revealed a gene called gasdermin E, which is downregulated in several cancers, aids cells in dying unexpectedly, and may also suppress tumor growth.
Emad Alnemri, Ph.D., the leader of the new study published in the journal Nature Communications and the Thomas Eakins endowed Professor of Biochemistry and Molecular Biology at Sidney Kimmel Cancer Center, said that they discovered that gasdermin E might be essential in controlling cancer growth.
In some gastric, breast, and colorectal cancers, gasdermin E gene expression is much lower than in healthy cells. Why cancers might turn down the expression of this gene was unknown. Dr. Alnemri and colleagues discovered in the previous study that gasdermin E participates in the cell death program when a cell death enzyme called caspase-3 cleaves it. The researchers discovered that the cleaved gasdermin E creates holes in the outer membrane of the cell. The holes cause the cell to swell and burst. The thought of the researchers was that such a mechanism could be at work in cancerous cells.
The death of the cell makes them undergo a series of coordinated, pre-programmed steps to self-destruct in a process known as apoptosis. When Dr. Alnemri and his group treated cancer cells with a chemotherapy drug that sets the death cascade in motion, they discovered that gasdermin E advances apoptosis by forming holes, not only in the cell membrane but also in the membrane of organelles essential for life, the mitochondria, the cell's powerhouse. When gasdermin E pokes holes in mitochondria, it unleashes the proteins that carry out the final phases of programmed cell death.
Dr. Alnemri pointed out that they found that cells with gasdermin E grow less and are more susceptible to death. He said that they don't form tumors as well wither, while the cells that lack this protein form bigger tumors and kill the mice much faster.
The study's finding suggests that gasdermin E limits cancer growth and progression and may serve as a way to tell whether a tumor is fast growing. The lead researcher maintained that gasdermin E could be used as a marker to distinguish aggressive tumors from less aggressive ones. Aggressive tumors may have no gasdermin E, but less aggressive one could have more. Also, the information could be used to decide how to design effective strategies to treat cancer.
