New evidence reported by researchers at Roswell Park Cancer Institute lends support to the hypothesis that the SSeCKS/AKAP12 gene is a key inhibitor of prostate cancer metastasis. The data are some of the first to demonstrate this dynamic in transgenic animal models, with promising implications for development of targeted therapies for prostate cancer and perhaps for other solid-tumor cancers.
The Roswell team notes that aggressive prostate cancers in humans typically turn off or delete two major regulatory genes, SSeCKS/AKAP12 and Rb. To explore this dynamic, the researchers developed a transgenic animal model to study the effects of deleting these two genes on prostate cancer progression. They report in Cancer Research that the loss of these two genes and associated protein products leads to early prostate cancer. Moreover, more than 80% of the transgenic models in their study developed metastatic lesions in lymph nodes near the prostate.
“This correlates with our earlier finding that SSeCKS/AKAP12 inhibits the chemotaxis of metastatic prostate tumor cells—that is, their ability to move on to another environment in response to chemical attractants,” says lead author Irwin Gelman, PhD. “Thus, our data suggest that SSeCKS plays a role in preventing the early dissemination of prostate cancer cells to metastatic sites. Importantly, we show that humans whose prostate cancers have turned off or deleted the SSeCKS/AKAP12 gene have significantly higher rates of metastasis formation compared to cases where SSeCKS/AKAP12 levels are sustained.”
While the SSeCKS/AKAP12 gene is deleted in about one-third of metastatic prostate cancers, the remaining two-thirds of such tumors may be treatable with drugs that induce the reactivation of SSeCKS/AKAP12 production. Researchers are now seeking to identify the genomic signatures controlled by SSeCKS/AKAP12 in the suppression of metastasis pathways. Read the study abstract.
