Enzyme That Allows Brain Tumor Growth Discovered
26/05/2017
New findings explain how the enzyme ACSS2 aids tumors in a nutrient-starved environment offering potential new treatment approaches.
All cancer tumors have one thing in common – they must feed themselves to grow and spread, a difficult feat since they are usually in a tumor microenvironment with limited nutrients and oxygen. A study at The University of Texas MD Anderson Cancer Center has revealed new details about how an enzyme called acetyl-CoA synthetase 2 (ACSS2) allows brain tumors to grow despite their harsh surroundings. The findings, published in the May 25 online issue of Molecular Cell, portends ACSS2 as a potential player in new approaches to treating this often deadly disease.
ACSS2 provides tumors a competitive edge by enhancing their ability to use a cellular salt called acetate as a carbon-based food source rather than the more desirable glucose which is often in short supply in cancer cells. This lifeline allows cancer cells at the core of the tumor to survive and even grow as it battles with nutrient deficiency.
Current therapies and the body’s own immune system are not efficient at stopping this vital nutrient pathway in cancer cells, and little is known about how these life-giving proteins are transported from cytosol, a liquid cell component, into the nucleus via a process called nuclear translocation. The ability to halt nuclear translocation of ACSS2 would cut off the cancer cell’s self-maintaining ability at its most basic level. The study, led by Zhimin Lu, Ph.D., professor of Neuro-Oncology, provided new information about nuclear translocation and how ACSS2 may offer a new approach for therapy.
“Overcoming metabolic stress is a critical step in solid tumor growth. Acetyl coenzyme A (CoA) generated via glucose and acetate uptake is a key carbon source for important cellular processes such as histone acetylation and gene expression,” said Lu. “However, how acetyl CoA is produced under nutritional stress is unclear. Our study explains the underlying mechanics of how this occurs, with ACSS2 as a novel and important method for gene expression under these circumstances.”