Working with monkey and human cells, University of Minnesota researchers have begun to understand the intricacies of self-destructing cellular behavior.
Hormel Institute researchers have identified that cells that end up having the wrong number of chromosomes after faulty cellular divisions — an issue known as aneuploidy — can mark themselves and self-destruct.
Aneuploidy is commonly observed in diseases such as cancer. The findings are a step toward finding a way to prevent the failure of the cell’s self-destruction mechanism, which would help prevent aneuploidy and its resulting medical issues, said Edward Hinchcliffe, the lead author of the paper.
“The novelty is really in that they showed a chromosome gets marked,” said Jan van Deursen, a doctor in the Mayo Clinic’s Cancer Center. “It seems from the research that these chromsomes get modified, and that’s really innovative. … What they are showing is that if a cell makes a mistake in the segregation of chromosomes that chromosomes get marked.”
In 1998, scientists began recognizing that cells stopped growing when they have the wrong number of chromosomes, but many haven’t understood the triggers of this phenomena, Hinchcliffe said. The self-destruction mechanism differs from cell checkpoints that slow down processes but don’t stop it, he said. Hinchcliffe compares it to stop lights at an intersection. If all the lights are green, then a circuit is tripped, and it switches the lights flashing red.
“If you’ve made some catastrophic mistake, you trip a circuit that stops everything,” he said. “And that’s what’s happening here.”
Hinchcliffe said that there have been a variety of theories for understanding the way in which cells sense and respond to faulty chromosomal separation.
“One possibility is that they actually count their chromosomes, but rather than counting them all, they simply count the one [that’s in the wrong place],” he said.
By exposing their test cells to low temperatures, Hinchcliffe said they were able to change the complexion of the cell which led to an intentional occurrence of aneuploidy.
“And what we think is going on is that when they are alone, [the chromosomes] trigger a biochemical sensor,” he said. “That sensor then functions through a chemical pathway that signals for the cell to stop growing.”
Van Deursen said continued aneuploidy research can help improve treatment of the diseases it causes, like cancer.
“If you think of chemo [therapy], maybe .1 percent of the cells doesn’t get killed. The aneuploidy seems to help cells find ways around the toxic drugs to stay alive and thrive. … This aneuploidy has something to do with this resistance,” van Deursen said.
