In Science this week, two independent research groups publish the crystal structures of the bacterial translocator protein (TSPO), a membrane protein that binds steroids and porphyrins and is implicated in various diseases. In the first study, a team from Columbia University shows that a mutant form of TSPO mimics a human mutation associated with psychiatric disorders and has structural changes in a region associated in cholesterol binding. In the other study, a group from Michigan State University presents data showing how TSPO catalyzes the degradation of porphyrins, which could be important in protecting against oxidative stress.
Meanwhile, in Science Translational Medicine, a group led by researchers from the University of Torino Medical School present data showing how overexpression of a protein can lead to drug resistance in colorectal cancer patients. While drugs inhibiting epidermal growth factor receptor (EGFR) can be quite effective against the disease, many patients develop resistance to the treatment. The researchers tested various EGFR inhibitors in mice carrying tumors from 125 patients with treatment-resistant colorectal cancer and found that resistance was associated with overexpression of insulin-like growth factor 2 (IGF2). Blocking IGF2 in these tumors restored their sensitivity to EGFR inhibitors, the researchers report.