The action and activity of proteins in cancerous cells is an area of study that has provided us with many therapeutic targets. However, the targeted activation of tumor-suppressor proteins has not been readily achieved in the clinic. Now, research into EphB3, a protein that is overexpressed in non-small-cell lung cancer (NSCLC), has led to the surprising discovery that phosphorylation of this protein by EphB3 kinase 'turns' it into a tumor-suppressor protein.

The researchers, led by Dong Xie at the Shanghai Institutes for Biological Sciences, used patient-derived paired normal and NSCLC cell lines to investigate the mechanism behind this observation. They identified a novel binding protein for EphB3 kinase—the receptor for activated C-kinase 1—and showed that this protein mediates formation of a signaling complex that was associated with inhibition of metastasis.