Cancer-promoting pathway thwarted by researchers
The study's research team, led by Hui-Kuan Lin, PhD, an assistant professor in M.D. Anderson's Department of Molecular and Cellular Oncology, was able to show that overexpression of the gene RhoA, or three of its transcription complex components, was strongly associated with metastatic disease.
“There are four components to this complex, which starts RhoA expression by transcribing the gene, and we found that all of them are important to metastasis,” Dr. Lin said. “Knock down any one of the four, and you can stop breast cancer metastasis by preventing RhoA expression.”
To come to their discovery, researchers identified that knocking down the Myc protein in cancer cell lines decreased RhoA expression, cell migration and invasion, while Myc overexpression increased all three. Then they discovered that the overexpression of Skp2 also resulted in more RhoA and that both Skp2 and Myc were required for the metastasis-producing RhoA to be overexpressed. In the end, experiments in a mouse model of breast cancer metastasis to the lung showed that deficiency of either Myc, Skp2, or Miz1 restricted metastasis, while overexpression of each of the three proteins increased cell migration and invasion.
“Right now, there are no small-molecule agents to inhibit any of these targets,” Dr. Lin concluded. “One future direction of research will be to find ways to target the entire transcription complex or its individual components.”