When the researchers were evaluating potential links between telomeres and the risk of cancer they discovered that telomeres act as end caps on the end of chromosomes to ensure the genetic structures don’t merge. As a cell makes a copy of its DNA during cell division telomeres get shorter, and eventually become too short to protect the chromosomes then the cell receives a signal to halt cell division. Sometimes the cells will not receive this signal and they continue to keep dividing until the telomere caps become too short or go missing then the cell will enter a state of crisis when their uncapped chromosomes fuse and malfunction, as in cancer cells.
This state of cell crisis often causes cells to die in droves which stops pre-cancer cells from developing into full blown cancer which led the team to investigate this crisis state to examine the mechanisms of this beneficial process.
“Many researchers assumed cell death in crisis occurs through apoptosis, which along with autophagy is one of two types of programmed cell death. But no one was doing experiments to find out if that was really the case.”
In experiments with human cells the team deactivated tumor suppressor genes that impose a limit on cell division to observe cells dividing nonstop until their telomeres caps became dangerously short and triggered the crisis state. Markers of apoptosis and autophagy were investigated next to determine which of these two processes kills cells in crisis. The researchers found that while they both contributed to the death of a small number of normal cells autophagy was the primary cause of cell death during crisis.
When testing the consequences of stopping autophagy during crisis the cells were observed to continue to divide since they could not die through autophagy. The chromosomes of the endlessly replicating cells eventually ended up being fused and deformed, and the DNA damage resembled genetic damage found in cancerous cells.
Next the researchers inflicted DNA damage to healthy cells by intentionally damaging either the telomeres or the middle regions of the chromosomes; cells with damaged telomeres were observed to undergo autophagy and cells with damaged chromosomes underwent apoptosis.
As published in Nature the researchers concluded that autophagy is a mechanism that destroys precancerous cells which is activated when cells incur DNA damage or when telomeres are too short/missing based on their findings. Autophagy is still a valid strategy even after cancer has begun, which can be used to kill a tumor by starving it.
