Abstract
Cellular communication plays a critical role in diverse aspects of tumorigenesis including tumor cell growth/death, adhesion/detachment, migration/invasion, angiogenesis, and metastasis. G protein-coupled receptors (GPCRs) which constitute the largest group of cell surface receptors are known to play fundamental roles in all these processes. When considering the importance of GPCRs in tumorigenesis, the adhesion GPCRs (aGPCRs) are unique due to their hybrid structural organization of a long extracellular cell-adhesive domain and a seven-transmembrane signaling domain. Indeed, aGPCRs have been increasingly shown to be associated with tumor development by participating in tumor cell interaction and signaling. ADGRG1/GPR56, a representative tumor-associated aGPCR, is recognized as a potential biomarker/prognostic factor of specific cancer types with both tumor-suppressive and tumor-promoting functions. We summarize herein the latest findings of the role of ADGRG1/GPR56 in tumor progression.
Highlights
IntroductionPublisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations
Deletion of the PLL domain increases the signaling activity of GPR56 [26]. These results strongly suggest that the activation of GPR56 is mostly mediated via the dissociation/conformational change of the NTF
Several GPR56-specific monobodies were found to activate the same GPR56-F385A mutant efficiently [47]. These results indicated that these specific agonists bind to the extracellular region (ECR) of GPR56 and cause a unique conformational change that activates the receptor without the need of its proteolytic modification, supporting the GPS
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. The extracellular region (ECR) of most aGPCRs is uncommonly large and often consists of diverse cell-adhesive protein modules such as the epidermal growth factor (EGF)-like, immunoglobulin (Ig)-like, and lectin-like domains at its N-terminal half. These protein modules normally function as the binding sites for specific cellular ligands and/or binding partners of aGPCRs [10,11]. The activation and signaling mechanisms of aGPCRs are multifaceted, including the GPS cleavage-dependent and -independent as well as NTF-CTF dissociationGPCR proteolysis site (GPS) modes within [10,15,16,17].
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