Characterization of a novel EPHB2 mutant with respect to its proteolytic cleavage

The EphB receptors and their ligands have been shown to have both proliferation promoting and tumor suppressing roles. Here, we use cancer cell models to study how EPHB2 mutations affect colorectal cancer progression.

Aim

The aim is to clarify the role of Eph receptor mutations in colorectal cancer tumorigenesis.

Background

The Eph receptors constitute the largest subgroup of tyrosine kinase receptors. They are part of a bi-directional signaling pathway where their ephrin ligands, which either are transmembrane proteins or attached to the cell membrane with a GPI anchor, are also capable of signaling. These receptors and ligands are best known for their roles in axon guidance and cell migration. EphB receptors are paradoxical receptors in that they promote proliferation in normal intestinal epithelium but also act as tumor suppressors in colon cancer development. 

In a recent study, we found a mutation at the cleavage site in the ligand-binding domain of the EPHB2 in metastatic human colon cancer samples. The affected arginine residue is conserved in 11 of 14 human Eph receptors. Furthermore, there were 12 reported mutations in this residue when looking into all cancers of the TCGA dataset. Together, these observations suggest that this EPHB2 mutation can have a role in cancer development. In the project, we therefore study the function of the mutation through experiments on cell lines.

Project plan 

We are studying how the identified EPHB2 mutation affects human CRC progression, particularly at the metastatic phase of tumor development. To help us with this, we are looking for students who want to study cell signaling in cancer through study of EPHB2 wild type and mutant overexpressing cell lines. Techniques used in the project include qPCR, western blot, cell culture and growth curve analysis, confocal microscopy, and specific receptor cleavage assays.

CONTACT DETAILS

Professor Tobias Sjöblom
E-mail: tobias.sjoblom@igp.uu.se
Read more about our research here.