A Melbourne-based research team has discovered a genetic defect that can halt cell growth and force cells into a death-evading survival state.
The finding has revealed an important mechanism controlling the growth of rapidly-dividing cells that may ultimately lead to the development of new treatments for diseases including cancer.
The discovery was made by Associate Professor Joan Heath, Dr Yeliz Boglev and colleagues at the Melbourne-Parkville Branch of the Ludwig Institute for Cancer Research. Dr Kate Hannan, Associate Professor Rick Pearson and Associate Professor Ross Hannon at the Peter MacCallum Cancer Centre, also contributed to the work, which was published in the journal PLOS Genetics this month.
Associate Professor Heath, a Ludwig Institute Member who recently transferred her research group to the Walter and Eliza Hall Institute, said the discovery was made while studying zebrafish embryos that harbour genetic mutations which prevent rapid cell growth during organ development.
"Zebrafish embryos provide us with a great laboratory model for these studies because they are transparent, an attribute that allows us to track the growth of rapidly developing organs in live animals under a simple microscope. Moreover, the genes controlling growth and proliferation of developing tissues are essentially identical in zebrafish and humans, and are known to be frequently commandeered by cancer cells.
"We discovered that a mutation in a relatively under-studied gene called pwp2h leads to the faulty assembly of ribosomes, the 'protein factories' of cells, and stops cells from dividing," she said. "What was intriguing was that cells under stress from ribosome failure did not die. Instead, the cells switched on a survival mechanism called autophagy and began obtaining nutrients by digesting their own intracellular components."
Ribosomes are large molecular machines in cells that manufacture proteins, and are critical for cell growth and division. Currently, there is great interest in developing therapeutics to block ribosome production, as a strategy to prevent cancer cells from dividing.