An international team of researchers has discovered the energy production mechanism of cancerous cells that drives the growth of the nucleolus and causes tumors to rapidly multiply. The study authors believe that the findings, published in Nature Cell Biology, could lead to the development of new cancer treatments to stop tumor growth.
 
Although it was discovered nearly 100 years ago that nucleoli enlarge in cancer cells and that enlargement leads to a ribosome increase, little was known about exactly how the nucleolus produces a massive amount of ribosome in cancerous cells.
 
“Nucleolus enlargement is a telltale sign of cancer, and its size has long been used as a yardstick to determine how advanced cancer is in patients," said Atsuo Sasaki, PhD, lead investigator.
 
The researchers examined the energy pathways in malignant brain tumors and glioblastoma in animal models followed by cohort studies for human specimen. The results demonstrated an increased level of inosine monophosphate dehydrogenase (IMPDH) in cancer cells. This has been found to accelerate the production of guanosine triphosphate (GTP), a nucleotide that is among the building blocks needed to create RNA, which is prevalent in cancerous cells.
 
According to Sasaki, the nucleolus quickly expands by devouring GTP.
 
"We were surprised to find out that among all types of energy that could be used for cell growth, it's GTP that spikes and plays the most crucial role in ribosome increases that are associated with nucleolus enlargement in cancer cells. We knew right away that this was a substantial discovery that would require a sweeping range of expertise to understand what it truly meant," Sasaki added.
 
The discovery of the close relationship between IMPDH and the nucleolus prompted the researchers to develop a new method of metabolic analysis, which enabled them to obtain critical data for demonstrating that GTP produced from IMPDH activities is used for the nucleolus's ribosome synthesis. This led to the discovery of a clear correlation between the suppression of glioblastoma cell growth and IMPDH inhibition.
 
 
Reference
  1. UC researchers unlock cancer cells’ feeding mechanism [news release]. University of Cincinnati. Published August 1, 2019. https://www.uc.edu/news/articles/2019/08/n20846510.html. Accessed August 2, 2019.