The University of Texas MD Anderson Cancer Center, researchers have discovered that a protein involved in the immune response to microbes can also fuel cancer development and suppress the immune response to the disease. Working on mouse models of lung cancer, the group discovered TANK-binding kinase 1 (TBK1), and its adaptor protein TBK-binding protein 1 (TBKBP1) contributes to tumorigenesis when they’re activated by growth factors quite than by innate immune mechanisms. Their findings are reported today in Nature Cell Biology.
The latest research indicated that TBK1, which usually mediates induction of type 1 interferon in response to viruses or bacteria, additionally promotes the survival and reproduction of KRAS-dependent most cancers cells. Sun and colleagues set out to determine TBK1’s impact on cancer cells and its function in cancer development in vivo.
They first discovered that knocking out TBK1 in a mouse model designed to spontaneously develop lung cancer driven by KRAS mutations sharply decreased the number and size of tumors. Knockdown in a human lung cancer line promoted programmed cell death and suppressed tumor growth.
In a collection of experiments, the researchers showed that TBK1 and TBKBP1 form a growth factor signaling axis that activates mTORC1 to advertise tumor development. The pathway consists of TBKBP1 recruiting TBK1 to protein kinase C-theta (PKCθ), by way of a scaffold protein referred to as CARD10, enabling PKCθ to activate TBK1.
Whereas amlexanox has been examined in a clinical trial for the treatment of type 2 diabetes and weight problems like obesity, there are not any scientific trials open to testing the drug against cancer. Sun says his group continues preclinical research essential to put the groundwork for clinical trials, including analysis to find out whether or not amlexanox may work against different cancer types.