Adhesion GPCRs in Tumorigenesis.
Alterations in the homeostasis of several adhesion GPCRs (aGPCRs) have been observed in cancer. The main cellular functions regulated by aGPCRs are cell adhesion, migration, polarity, and guidance, which are all highly relevant to tumor cell biology. Expression of aGPCRs can be induced, increased, decreased, or silenced in the tumor or in stromal cells of the tumor microenvironment, including fibroblasts and endothelial and/or immune cells. For example, ADGRE5 (CD97) and ADGRG1 (GPR56) show increased expression in many cancers, and initial functional studies suggest that both are relevant for tumor cell migration and invasion. aGPCRs can also impact the regulation of angiogenesis by releasing soluble fragments following the cleavage of their extracellular domain (ECD) at the conserved GPCR-proteolytic site (GPS) or other more distal cleavage sites as typical for the ADGRB (BAI) family. Interrogation of in silico cancer databases suggests alterations in other aGPCR members and provides the impetus for further exploration of their potential role in cancer. Integration of knowledge on the expression, regulation, and function of aGPCRs in tumorigenesis is currently spurring the first preclinical studies to examine the potential of aGPCR or the related pathways as therapeutic targets.
Department of Surgery, Research Laboratories, University of Leipzig, Liebigstraße 19, Leipzig, 04103, Germany. gabriela.aust@medizin.uni-leipzig.de.
Gabriela
G
Aust
Department of Neurosurgery and Hematology & Medical Oncology, School of Medicine and Winship Cancer Institute, Emory University, Atlanta, GA, 30322, USA.
Dan
D
Zhu
Department of Neurosurgery and Hematology & Medical Oncology, School of Medicine and Winship Cancer Institute, Emory University, Atlanta, GA, 30322, USA.
Erwin G
EG
Van Meir
Department of Biomedical Genetics, University of Rochester Medical Center, Rochester, NY, 14642, USA.
Lei
L
Xu
D000818:Animals; D001665:Binding Sites; D002448:Cell Adhesion; D002462:Cell Membrane / Q000378:metabolism*; D002465:Cell Movement; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000378:metabolism* / Q000473:pathology; D003198:Computer Simulation; D057225:Data Mining; D030562:Databases, Protein; D006801:Humans; D008958:Models, Molecular; D009361:Neoplasm Invasiveness; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D009389:Neovascularization, Pathologic; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction; D013329:Structure-Activity Relationship
D043562:Receptors, G-Protein-Coupled
Metastasis; Tumor angiogenesis; Tumor cell migration; Tumor invasion; Tumor therapy