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GPR56 Interacts with Extracellular Matrix and Regulates Cancer Progression

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Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 706)

Abstract

GPR56 is a relatively recent addition to the adhesion-GPCR family. Genetic and biochemical studies uncovered its roles in cancer and development and established its function as an adhesion receptor to mediate the interactions between cells and extracellular matrix. Despite of much progress on understanding its biological implications, the mechanism of its function remains elusive. It has not been firmly established whether GPR56 signals directly through G proteins and what its upstream stimuli and downstream effectors are to execute its various biological effects. This chapter will give an overview of the primary structures of the Gpr56 gene and its encoded protein and attempt to point out open questions in this research area, with an emphasis on its roles in cancer and signal transduction.

Keywords

Human Melanoma Cell Line Tissue Transglutaminase Stem Cell Maintenance Neuronal Progenitor Cell GPR56 Gene 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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References

  1. 1.
    Liu M, Parker RM, Darby K et al. GPR56, a novel secretin-like human G-protein-coupled receptor gene. Genomics 1999; 55(3):296–305.PubMedCrossRefGoogle Scholar
  2. 2.
    Zendman AJ, Cornelissen IM, Weidle UH et al. TM7XN1, a novel human EGF-TM7-like cDNA, detected with mRNA differential display using human melanoma cell lines with different metastatic potential. FEBS Lett 1999; 446(2-3):292–298.PubMedCrossRefGoogle Scholar
  3. 3.
    Xu L, Begum S, Hearn JD et al. GPR56, an atypical G protein-coupled receptor, binds tissue transglutaminase, TG2 and inhibits melanoma tumor growth and metastasis. Proc Natl Acad Sci USA 2006; 103(24):9023–9028.PubMedCrossRefGoogle Scholar
  4. 4.
    Li S, Jin Z, Koirala S et al. GPR56 regulates pial basement membrane integrity and cortical lamination. J Neurosci 2008; 28(22):5817–5826.PubMedCrossRefGoogle Scholar
  5. 5.
    Piao X, Hill RS, Bodell A et al. G protein-coupled receptor-dependent development of human frontal cortex. Science 2004; 303(5666):2033–2036.PubMedCrossRefGoogle Scholar
  6. 6.
    Koirala S, Jin Z, Piao X et al. GPR56-regulated granule cell adhesion is essential for rostral cerebellar development. J Neurosci 2009; 29(23):7439–7449.PubMedCrossRefGoogle Scholar
  7. 7.
    Yona S, Lin HH, Siu WO et al. Adhesion-GPCRs: emerging roles for novel receptors. Trends Biochem Sci 2008; 33(10):491–500.PubMedCrossRefGoogle Scholar
  8. 8.
    Lagerstrom MC, Schioth HB. Structural diversity of G protein-coupled receptors and significance for drug discovery. Nat Rev Drug Discov 2008; 7(4):339–357.PubMedCrossRefGoogle Scholar
  9. 9.
    Terskikh AV, Easterday MC, Li L et al. From hematopoiesis to neuropoiesis: evidence of overlapping genetic programs. Proc Natl Acad Sci USA 2001; 98(14):7934–7939.PubMedCrossRefGoogle Scholar
  10. 10.
    Terskikh AV, Miyamoto T, Chang C et al. Gene expression analysis of purified hematopoietic stem cells and committed progenitors. Blood 2003; 102(1):94–101.PubMedCrossRefGoogle Scholar
  11. 11.
    Jin Z, Tietjen I, Bu L et al. Disease-associated mutations affect GPR56 protein trafficking and cell surface expression. Hum Mol Genet 2007; 16(16):1972–1985.PubMedCrossRefGoogle Scholar
  12. 12.
    Cyster J, Somoza C, Killeen N et al. Protein sequence and gene structure for mouse leukosialin (CD43), a T-lymphocyte mucin without introns in the coding sequence. Eur J Immunol 1990; 20(4):875–881.PubMedCrossRefGoogle Scholar
  13. 13.
    Corral L, Singer MS, Macher BA et al. Requirement for sialic acid on neutrophils in a GMP-140 (PADGEM) mediated adhesive interaction with activated platelets. Biochem Biophys Res Commun 1990; 172(3):1349–1356.PubMedCrossRefGoogle Scholar
  14. 14.
    Stacey M, Lin HH, Gordon S et al. LNB-TM7, a group of seven-transmembrane proteins related to family-B G-protein-coupled receptors. Trends Biochem Sci 2000; 25(6):284–289.PubMedCrossRefGoogle Scholar
  15. 15.
    Krasnoperov VG, Bittner MA, Beavis R et al. Alpha-latrotoxin stimulates exocytosis by the interaction with a neuronal G-protein-coupled receptor. Neuron 1997; 18(6):925–937.PubMedCrossRefGoogle Scholar
  16. 15a.
    Lin H, Chang G, Davies J et al. Autocatalytic cleavage of the EMR2 receptor occurs at a conserved G protein-coupled receptor proteolytic site motif. JBC 2004; 279(30): 31823–31832.CrossRefGoogle Scholar
  17. 16.
    Paulus H. Protein splicing and related forms of protein autoprocessing. Annu Rev Biochem 2000; 69:447–496.PubMedCrossRefGoogle Scholar
  18. 17.
    Krasnoperov V, Bittner MA, Holz RW et al. Structural requirements for alpha-latrotoxin binding and alpha-latrotoxin-stimulated secretion. Astudy with calcium-independentreceptor of alpha-latrotoxin (CIRL) deletion mutants. J Biol Chem 1999; 274(6):3590–3596.PubMedCrossRefGoogle Scholar
  19. 18.
    Xu L, Hynes RO. GPR56 and TG2: possible roles in suppression of tumor growth by the microenvironment. Cell Cycle 2007; 6(2):160–165.PubMedCrossRefGoogle Scholar
  20. 19.
    Fidler IJ. The pathogenesis of cancer metastasis: the’ seed and soil’ hypothesis revisited. Nat Rev Cancer 2003; 3(6):453–458.PubMedCrossRefGoogle Scholar
  21. 20.
    Morrison SJ, Spradling AC. Stem cells and niches: mechanisms that promote stem cell maintenance throughout life. Cell 2008; 132(4):598–611.PubMedCrossRefGoogle Scholar
  22. 21.
    Shashidhar S, Lorente G, Nagavarapu U et al. GPR56 is a GPCR that is overexpressed in gliomas and functions in tumor cell adhesion. Oncogene 2005; 24(10):1673–1682.PubMedCrossRefGoogle Scholar
  23. 22.
    Sud N, Sharma R, Ray R et al. Differential expression of G-protein coupled receptor 56 in human esophageal squamous cell carcinoma. Cancer Lett 2006; 233(2):265–270.PubMedCrossRefGoogle Scholar
  24. 23.
    Ke N, Sundaram R, Liu G et al. Orphan G protein-coupled receptor GPR56 plays a role in cell transformation and tumorigenesis involving the cell adhesion pathway. Mol Cancer Ther 2007; 6(6):1840–1850.PubMedCrossRefGoogle Scholar
  25. 24.
    Joyce JA, Pollard JW. Microenvironmental regulation of metastasis. Nat Rev Cancer 2009; 9(4):239–252.PubMedCrossRefGoogle Scholar
  26. 25.
    Hynes RO. Cell-matrix adhesion in vascular development. J Thromb Haemost 2007; 5(Suppl 1):32–40.PubMedCrossRefGoogle Scholar
  27. 26.
    Lorand L, Graham RM. Transglutaminases: crosslinking enzymes with pleiotropic functions. Nat Rev Mol Cell Biol 2003; 4(2):140–156.PubMedCrossRefGoogle Scholar
  28. 27.
    Kotsakis P, Griffin M. Tissue transglutaminase in tumour progression: friend or foe? Amino Acids 2007; 33(2):373–384.PubMedCrossRefGoogle Scholar
  29. 28.
    Haroon ZA, Lai TS, Hettasch JM et al. Tissue transglutaminase is expressed as a host response to tumor invasion and inhibits tumor growth. Lab Invest 1999; 79(12):1679–1686.PubMedGoogle Scholar
  30. 29.
    Mangala LS, Arun B, Sahin AA et al. Tissue transglutaminase-induced alterations in extracellular matrix inhibit tumor invasion. Mol Cancer 2005; 4:33.PubMedCrossRefGoogle Scholar
  31. 30.
    Jones RA, Kotsakis P, Johnson TS et al. Matrix changes induced by transglutaminase 2 lead to inhibition of angiogenesis and tumor growth. Cell Death Differ 2006; 13(9):1442–1453.PubMedCrossRefGoogle Scholar
  32. 31.
    Verderio E, Gaudry C, Gross S et al. Regulation of cell surface tissue transglutaminase: effects on matrix storage of latent transforming growth factor-beta binding protein-1. J Histochem Cytochem 1999; 47(11):1417–1432.PubMedCrossRefGoogle Scholar
  33. 32.
    Kojima S, Nara K, Rifkin DB. Requirement for transglutaminase in the activation of latent transforming growth factor-beta in bovine endothelial cells. J Cell Biol 1993; 121(2):439–448.PubMedCrossRefGoogle Scholar
  34. 33.
    Lorand L, Dailey JE, Turner PM. Fibronectin as a carrier for the transglutaminase from human erythrocytes. Proc Natl Acad Sci USA 1988; 85(4):1057–1059.PubMedCrossRefGoogle Scholar
  35. 34.
    Akimov SS, Krylov D, Fleischman LF et al. Tissue transglutaminase is an integrin-binding adhesion coreceptor for fibronectin. J Cell Biol 2000; 148(4):825–838.PubMedCrossRefGoogle Scholar
  36. 35.
    Akimov SS, Belkin AM. Cell surface tissue transglutaminase is involved in adhesion and migration of monocytic cells on fibronectin. Blood 2001; 98(5):1567–1576.PubMedCrossRefGoogle Scholar
  37. 36.
    De Laurenzi V, Melino G. Gene disruption of tissue transglutaminase. Mol Cell Biol 2001; 21(1):148–155.PubMedCrossRefGoogle Scholar
  38. 37.
    Nanda N, Iismaa SE, Owens WA et al. Targeted inactivation of Gh/tissue transglutaminase II. J Biol Chem 2001; 276(23):20673–20678.PubMedCrossRefGoogle Scholar
  39. 38.
    Little KD, Hemler ME, Stipp CS. Dynamic regulation of a GPCR-tetraspanin-G protein complex on intact cells: central role of CD81 in facilitating GPR56-Galpha q/11 association. Mol Biol Cell 2004; 15(5):2375–2387.PubMedCrossRefGoogle Scholar
  40. 39.
    Hemler ME. Targeting of tetraspanin proteins—potential benefits and strategies. Nat Rev Drug Discov 2008; 7(9):747–758.PubMedCrossRefGoogle Scholar
  41. 40.
    Ikeyama S, Koyama M, Yamaoko MS et al. Suppression of cell motility and metastasis by transfection with human motility-related protein (MRP-1/CD9) DNA J Exp Med 1993; 177(5):1231–1237.PubMedCrossRefGoogle Scholar
  42. 41.
    Takeda T, Hattori N, Tokuhara T et al. Adenoviral transduction of MRP-1/CD9 and KAI1/CD82 inhibits lymph node metastasis in orthotopic lung cancer model. Cancer Res 2007; 67(4):1744–1749.PubMedCrossRefGoogle Scholar
  43. 42.
    Saito Y, Tachibana I, Takeda Y et al. Absence of CD9 enhances adhesion-dependentmorphologic differentiation, survival and matrix metalloproteinase-2 production in small cell lung cancer cells. Cancer Res 2006; 66(19):9557–9565.PubMedCrossRefGoogle Scholar
  44. 43.
    Feigelson SW, Grabovsky V, Shamri R et al. The CD81 tetraspanin facilitates instantaneous leukocyte VLA-4 adhesion strengthening to vascular cell adhesion molecule 1 (VCAM-1) under shear flow. J Biol Chem 2003; 278(51):51203–51212.PubMedCrossRefGoogle Scholar
  45. 44.
    Iguchi T, Sakata K, Yoshizaki K et al. Orphan G protein-coupled receptor GPR56 regulates neural progenitor cell migration via a G alpha 12/13 and Rho pathway. J Biol Chem 2008; 283(21):14469–14478.PubMedCrossRefGoogle Scholar

Copyright information

© Landes Bioscience and Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Department of Biomedical GeneticsUniversity of Rochester Medical CenterRochesterUSA

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