Tumor suppression via a nuclear cAMP signaling microdomain

cAMP has a long and complicated history as it relates to tumor growth and response to therapeutics. We have identified a novel nuclear specific cAMP microdomain that blocks the growth of multiple human and mouse cancer cell lines both in vitro and in vivo. This nuclear signaling domain is activated early in tumorigenesis and when lost leads to tumor growth and invasion. We have established that nuclear cAMP regulates a novel signaling cascade that inhibits the Hippo pathway and leads to EMT transition. Antibodies that detect this pathway in the nucleus have diagnostic and prognostic utility, and we are working to understand the mechanisms by which this pathway inhibits tumor growth, invasion, and response to therapy.