Adhesion G Protein-Coupled Receptors in Development and Diseases

The adhesion G protein-coupled receptors (GPCRs) are an enigmatic family of GPCRs that is highly conserved through evolution but poorly characterized. Their C-termini contain seven transmembrane domains resembling those in class B GPCRs and have been shown to signal through G proteins. But distinct from conventional GPCRs, the extracellular stalks of adhesion GPCRs often include motifs involved in cell adhesion and many were reported to interact with extracellular matrix. These receptors are thus considered a hybrid between adhesion receptors and GPCRs. Furthermore, in the juxtamembrane region of extracellular stalk of all adhesion GPCRs resides a GAIN domain (GPCR Autoproteolysis-INducing domain), which induces auto-cleavage of the receptor and hereby separates its extracellular stalk and transmembrane segments. The cleaved fragments could interact with each other non-covalently or function as independent entities, lending significant complexity to the regulatory mechanisms of adhesion GPCRs. Mutations in adhesion GPCRs had been found to associate with human diseases and knockout animals exhibit a variety of defects further supporting their functional importance during development and diseases.

Research in this area promises to reveal new insights on a variety of biological processes. This Research Topic welcomes contributions on the function of adhesion GPCRs in diseases, with a focus on cancer progression. Consideration will be preferentially provided for but not limited to studies on the signaling mechanisms and outcome of adhesion GPCRs in cancer cells, regulatory mechanisms of the protein or mRNA expression of adhesion GPCRs in cancer samples at different stages, the contribution of adhesion GPCRs to cancer development and progression in xenograft models or transgenic tumor models, and strategies to target adhesion GPCRs for cancer control and treatment.