Yale Researchers Describe Crossroads in Pathway to Cancer, Diabetes, Heart Disease

Yale University researchers have described a molecular traffic signal in the middle of a busy biological highway that influences such diverse processes as the production of insulin, activation of the immune system, creation of new brain cells and formation of tumors.

The centrality of this traffic signal, known as mTOR, makes it of intense interest to researchers searching for new treatments for a wide variety of diseases, said Michael Simons, M.D., chief of cardiology at Yale School of Medicine.

In a study appearing Friday in the journal Molecular Cell, a team led by Simons showed that a protein called syndecan-4 appears to activate mTORC2, one of two key mTOR protein complexes. Once mTORC2 is activated, it regulates a critical molecular pathway governed by an enzyme called Akt, which in turn controls the size, proliferation and survival of cells.

When syndecan-4 is disrupted, it decreases mTORC2 activity and increases activity of its cousin, mTOR1, which governs protein synthesis and cells’ response to oxygen deprivation.

Understanding the interaction between mTORC2 and Akt function opens new avenues to potentially regulating blood vessel growth in such conditions as cancer and coronary artery disease, Simons said.

Other authors from Yale contributing to the study are Chohreh Partovian, the lead author on the paper, Rong Ju, as well as Kathleen Martin and Zhen W. Zhuang from Dartmouth Medical School.

The National Institutes of Health funded the work.