X-ray structure of tumor suppressor OPCML

Congratulations to recently graduated PhD student Eloise Morecroft, whose work has been included in a new publication in Nature Communications

The publication - Inactivating mutations and X-ray crystal structure of the tumor suppressor OPCML reveal cancer-associated functions – is a result of a collaboration between Chiara Recchi and Hani Gabra from The Department of Surgery and Cancer and Lawrence Stern at The University of Massachusetts Medical School

OPCML (opioid binding protein call adhesion molecule-like) is a tumour suppressor protein anchored to the outer leaflet of the plasma membrane via a GPI (glycophosphatidylinositol) anchor. OPCML is a frequently inactivated tumour suppressor in numerous cancers including ovarian cancer. This new publication reports the crystal structure of OPCML to 2.65 Å resolution and the generation of a panel of OPCML variants with representative clinical mutations enabling mapping of diverse functions to distinct protein structural domains. The variants demonstrate clear phenotypic effects in vitro and in vivo including changes to anchorage-independent growth, oligomeric state, interaction with activated cognate receptor tyrosine kinases, cellular migration, invasion in vitro and tumor growth in vivo.

This project was funded by Ovarian Cancer Action  and Eloise’s PhD work was funded by the EPSRC through the Imperial College Centre for Doctoral Training.