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Adhesion GPCRs in Tumorigenesis

  • Gabriela AustEmail author
  • Dan Zhu
  • Erwin G. Van Meir
  • Lei Xu
Chapter
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 234)

Graphical Abstract

Abstract

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.

Keywords

Tumor cell migration Tumor invasion Metastasis Tumor angiogenesis Tumor therapy 

Abbreviations

CCLE

Cancer Cell Line Encyclopedia

CTF

C-terminal fragment

ECD

Extracellular domain

ECM

Extracellular matrix

GAIN

GPCR autoproteolysis inducing

GPS

GPCR-proteolytic site

NTF

N-terminal fragment

TG2

Tissue transglutaminase

TSR

Thrombospondin repeat

Notes

Acknowledgments

G.A. was supported by grants of the German Research Foundation (AU 132/7-3; FOR2149 Project 8 AU 132/8-1), L.X. by the National Institute of General Medicine Sciences (NIGMS; grant R01GM098591), D.Z. and E.G.V.M. in part by the US National Cancer Institute (grants CA086335 and NS096236), and the Southeastern Brain Tumor, Cure Childhood Cancer, and St. Baldrick’s Foundations.

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Copyright information

© Springer International Publishing AG 2016

Authors and Affiliations

  • Gabriela Aust
    • 1
    Email author
  • Dan Zhu
    • 2
  • Erwin G. Van Meir
    • 2
  • Lei Xu
    • 3
  1. 1.Department of Surgery, Research LaboratoriesUniversity of LeipzigLeipzigGermany
  2. 2.Department of Neurosurgery and Hematology & Medical OncologySchool of Medicine and Winship Cancer Institute, Emory UniversityAtlantaUSA
  3. 3.Department of Biomedical GeneticsUniversity of Rochester Medical CenterRochesterUSA

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