A collaborative research team led by scientists from Roswell Park Comprehensive Cancer Center and Wake Forest University Baptist Medical Center has determined that a GTPase called RAC1 actively recruits enzymes involved in nucleotide production to promote cancer metastasis.
The study was published in Nature Communications.
Using a combination of computer modeling and monitoring of cellular biosensors, Roswell Park researchers tagged the RAC1 protein in a preclinical model and found that it directly interacts with IMPDH2, an enzyme that helps provide cancer cells with building blocks to grow and spread. RAC1 then recruits IMPDH2 to cell membrane protrusions—a process pivotal for cancer cell invasion.
The study suggests that disabling RAC1 interactions could be an effective target for drugs or treatments to disrupt the various metabolic pathways that fuel metastasis, and the results offer a starting point for this goal by identifying the specific areas in which IMPDH2 and RAC1 connect.
“Not only do interactions with IMPDH2 represent an important mechanism of RAC1 activation in live cells, but by virtue of these interactions, other metabolic enzymes are recruited to the same locations to fuel cancer and metastasis,” lead author Anna Bianchi-Smiraglia, assistant professor of oncology in the Department of Cell Stress Biology at Roswell Park, said in a statement. “Disabling such interactions may provide a new strategy to suppress metastatic spread.”
