Issues

McKie and colleagues show that OPCML expression is silenced in multiple tumor types, including the vast majority of high-grade serous ovarian tumors, and correlates with poor prognosis. They further establish an extracellular mechanism of OPCML-mediated tumor suppression through negative regulation of a specific group of receptor tyrosine kinases (RTK). Through binding to RTK extracellular domains, OPCML induces RTK membrane redistribution, internalization, and degradation. Recombinant OPCML downregulated the same RTKs in vivo and inhibited ovarian cancer cell growth, suggesting that extracellular protein therapy may be useful in the treatment of OPCML-deficient tumors. For details, please see the article by McKie and colleagues on page 156.