Investigators from the Moffitt Cancer Center have made an important discovery that has the potential to significantly impact the future science of oncogenesis. Their findings, which were published in the Dec. 26 issue of PLoS One, show that that breast and lung cancer patients who have low levels of a tumor suppressing protein called tristetraprolin (TTP) have more aggressive tumors and a poorer prognosis than those with high levels of the protein.
Tumor suppressing proteins are encoded by tumor-suppressor genes, which are normal genes that slow down cell division, repair DNA mistakes, or shut off cellular functions through a process called apoptosis. When tumor suppressing genes become abnormal, it leads to a dysfunction in cellular growth that consequently results in cancer (oncogenesis).
Previous work done by this group had already shown that TTP functions as a tumor suppressor that impairs the development and disables the maintenance of a certain type of lymphoma. In this study however, they aimed to identify genes that could be associated with TTP tumor suppressor functions in human cancer. To meet their study aims they analyzed The Cancer Genome Atlas (TCGA), a detailed catalog of genetic changes in cancer developed by the National Institutes of Health, and compared patients who had low levels of TTP to those with high levels of the protein for breast cancer, lung adenocarcinoma, lung squamous cell carcinoma, and colon cancer datasets.
The data analysis showed a signature of 50 genes differentially regulated between high and low TTP-expressing tumors. Patients with low TTP-expressing breast cancer and lung adenocarcinoma where found to have decreased survival rates and more aggressive tumors with increased necrosis, demonstrating that TTP is involved in a variety of mechanisms important for tumor development and growth.
The authors emphasize that reduced levels of TTP could become a potential biomarker for human cancers with poor outcome. Dr. Robert Rounbehler, Ph.D., senior study author and research scientist at Moffitt, stated in a news release, “Identifying this network allows us to set up future research projects focused on understanding how TTP functions as a tumor suppressor with the ultimate goal of developing treatments specific for patients that have low levels of TTP.”