THE HIPPO PATHWAY

A basic science discovery made recently by researchers at Johns Hopkins University has revealed a fundamental way cells interpret signals from their environment and may eventually pave the way for potential new therapies.

The finding involves a signalling pathway in cells, called the Hippo pathway, which normally constrains cell division and regulates the size of organs, and also plays a role in tissue growth and development as well as tumour suppression.

The Hippo pathway normally works as a brake on cell division that stops organs from growing larger once they have reached the appropriate size. Mutations or other abnormalities in the pathway have been found in many cancers. The researchers clarified the working of this signalling pathway by solving a long-standing mystery of how one of its core components, an enzyme called MST2, can be activated. The Hippo pathway begins with the activation of two enzymes, MST1 and MST2. A variety of biological events, including cell-to-cell contacts, certain nutrients, stress, and signalling through cell receptors, can cause the enzymes to become activated. Once activated, the enzymes can send signals downstream to complete the signalling chain and inhibit cell division.

The researchers, led by Jennifer Kavran, assistant professor in the Bloomberg School’s Department of Biochemistry and Molecular Biology, showed for the first time that increasing the number of these enzymes helped stimulate their activation. The results should enhance the ability of researchers to manipulate the Hippo pathway signalling, for potential therapeutic applications for tissue regeneration and anti-cancer therapies.