Walter and Eliza Hall Institute researchers in Melbourne, Australia, have made a discovery that has upended scientists' understanding of programmed cell death and its role in tumour formation.
Programmed cell death, also called apoptosis, is an important process in human biology as it removes unwanted and damaged cells from our bodies. This process protects us against cancer development and autoimmune disease.
The research team's discovery, led by Professor Andreas Strasser from the institute's Molecular Genetics of Cancer Division, has implications for the understanding of how cancers develop and will inform the ongoing development of a new class of anti-cancer drugs called BH3 mimetics.
"Until now everybody believed that a failure of damaged cells to undergo suicide allowed mutated cells to proliferate, which contributes to tumour development," Professor Strasser said. "That's certainly still true but we discovered that, in certain settings, the opposite holds: the body's natural cell-suicide program can fuel tumour development."
The research team's experiments revealed that repeated cycles of cellular depletion and tissue regeneration, by activating stem cells, could promote tumour development.
In situations where the DNA in many cells is damaged, such as when the body is repeatedly exposed to low doses of radiation, there are repeated cycles of cell death in the body's tissues. "Attempts by the body's stem cells to repopulate the depleted tissue can then actually drive the tumour development," Professor Strasser said. "That's because the radiation, while killing many cells within a tissue, will create mutations in some of the surviving stem cells. When such abnormal (mutated) stem cells repopulate the tissue, they will divide many times and this can promote the development of tumours."
The research, done in collaboration with Dr Ewa Michalak, Dr Cassandra Vandenberg, Mr Alex Delbridge, Dr Li Wu, Dr C
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Walter and Eliza Hall Institute