Skip to main content
SpringerLink
Log in

Adhesion GPCRs in Tumorigenesis

  • Chapter
  • First Online:
Book cover Adhesion G Protein-coupled Receptors

Part of the book series: Handbook of Experimental Pharmacology ((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.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

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

References

  1. Krishnan A, Nijmeijer S, de Graaf C, Schiöth HB (2016) Classification, nomenclature and structural aspects of adhesion GPCRs. In: Langenhan T, Schöneberg T (eds) Adhesion G protein-coupled receptors: molecular, physiological and pharmacological principles in health and disease. Springer, Heidelberg

    Google Scholar 

  2. Kovacs P, Schöneberg T (2016) The relevance of genomic signatures at adhesion GPCR loci in humans. In: Langenhan T, Schöneberg T (eds) Adhesion G protein-coupled receptors: molecular, physiological and pharmacological principles in health and disease. Springer, Heidelberg

    Google Scholar 

  3. Araç D, Sträter N, Seiradake E (2016) Understanding the structural basis of adhesion GPCR functions. In: Langenhan T, Schöneberg T (eds) Adhesion G protein-coupled receptors: molecular, physiological and pharmacological principles in health and disease. Springer, Heidelberg

    Google Scholar 

  4. Nijmeijer S, Wolf S, Ernst OP, de Graaf C (2016) 7TM domain structure of adhesion GPCRs. In: Langenhan T, Schöneberg T (eds) Adhesion G protein-coupled receptors: molecular, physiological and pharmacological principles in health and disease. Springer, Heidelberg

    Google Scholar 

  5. Nieberler M, Kittel RJ, Petrenko AG, Lin H-H, Langenhan T (2016) Control of adhesion GPCR function through proteolytic processing. In: Langenhan T, Schöneberg T (eds) Adhesion G protein-coupled receptors: molecular, physiological and pharmacological principles in health and disease. Springer, Heidelberg

    Google Scholar 

  6. Langenhan T, Aust G, Hamann J (2013) Sticky signaling – Adhesion class G protein-coupled receptors take the stage. Sci Signal 6(276):re3. doi:10.1126/scisignal.2003825

    Article  PubMed  CAS  Google Scholar 

  7. Liebscher I, Schon J, Petersen SC, Fischer L, Auerbach N, Demberg LM et al (2014) A tethered agonist within the ectodomain activates the adhesion G protein-coupled receptors GPR126 and GPR133. Cell Rep 9:2018–2026

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Liebscher I, Schöneberg T (2016) Tethered agonism: a common activation mechanism of adhesion GPCRs. In: Langenhan T, Schöneberg T (eds) Adhesion G protein-coupled receptors: molecular, physiological and pharmacological principles in health and disease. Springer, Heidelberg

    Google Scholar 

  9. Kishore A, Hall RA (2016) Versatile signaling activity of adhesion GPCRs. In: Langenhan T, Schöneberg T (eds) Adhesion G protein-coupled receptors: molecular, physiological and pharmacological principles in health and disease. Springer, Heidelberg

    Google Scholar 

  10. Scholz N, Monk KR, Kittel RJ, Langenhan T (2016) Adhesion GPCRs as a putative class of metabotropic mechanosensors. In: Langenhan T, Schöneberg T (eds) Adhesion G protein-coupled receptors: molecular, physiological and pharmacological principles in health and disease. Springer, Heidelberg

    Google Scholar 

  11. Barretina J, Caponigro G, Stransky N, Venkatesan K, Margolin AA, Kim S et al (2012) The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity. Nature 483:603–607

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Cerami E, Gao J, Dogrusoz U, Gross BE, Sumer SO, Aksoy BA et al (2012) The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data. Cancer Discov 2:401–404

    Article  PubMed  Google Scholar 

  13. Gao J, Aksoy BA, Dogrusoz U, Dresdner G, Gross B, Sumer SO et al (2013) Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Sci Signal 6(269):pl1. doi:10.1126/scisignal.2004088

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. Uhlen M, Fagerberg L, Hallstrom BM, Lindskog C, Oksvold P, Mardinoglu A et al (2015) Proteomics. Tissue-based map of the human proteome. Science 347(6220):1260419. doi:10.1126/science.1260419

    Article  PubMed  CAS  Google Scholar 

  15. Aguirre-Gamboa R, Gomez-Rueda H, Martinez-Ledesma E, Martinez-Torteya A, Chacolla-Huaringa R, Rodriguez-Barrientos A et al (2013) SurvExpress: an online biomarker validation tool and database for cancer gene expression data using survival analysis. PLoS One 8(9), e74250. doi:10.1371/journal.pone.0074250

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Aust G, Eichler W, Laue S, Lehmann I, Heldin N-E, Lotz O et al (1997) CD97: a dedifferentiation marker in human thyroid carcinomas. Cancer Res 57:1798–1806

    CAS  PubMed  Google Scholar 

  17. Zendman AJ, Cornelissen IM, Weidle UH, Ruiter DJ, van Muijen GN (1999) TM7XN1, a novel human EGF-TM7-like cDNA, detected with mRNA differential display using human melanoma cell lines with different metastatic potential. FEBS Lett 446:292–298

    Article  CAS  PubMed  Google Scholar 

  18. Mallawaaratchy DM, Buckland ME, McDonald KL, Li CC, Ly L, Sykes EK et al (2015) Membrane proteome analysis of glioblastoma cell invasion. J Neuropathol Exp Neurol 74:425–441

    Article  CAS  PubMed  Google Scholar 

  19. Coustan-Smith E, Song G, Clark C, Key L, Liu P, Mehrpooya M et al (2011) New markers for minimal residual disease detection in acute lymphoblastic leukemia. Blood 117:6267–6276

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Davidson B, Stavnes HT, Risberg B, Nesland JM, Wohlschlaeger J, Yang Y et al (2012) Gene expression signatures differentiate adenocarcinoma of lung and breast origin in effusions. Hum Pathol 43:684–694

    Article  CAS  PubMed  Google Scholar 

  21. Kan Z, Jaiswal BS, Stinson J, Janakiraman V, Bhatt D, Stern HM et al (2010) Diverse somatic mutation patterns and pathway alterations in human cancers. Nature 466:869–873

    Article  CAS  PubMed  Google Scholar 

  22. Saito Y, Kaneda K, Suekane A, Ichihara E, Nakahata S, Yamakawa N et al (2013) Maintenance of the hematopoietic stem cell pool in bone marrow niches by EVI1-regulated GPR56. Leukemia 27:1637–1649

    Article  CAS  PubMed  Google Scholar 

  23. Silveira VS, Scrideli CA, Moreno DA, Yunes JA, Queiroz RG, Toledo SC et al (2013) Gene expression pattern contributing to prognostic factors in childhood acute lymphoblastic leukemia. Leuk Lymphoma 54:310–314

    Article  CAS  PubMed  Google Scholar 

  24. Charfi C, Edouard E, Rassart E (2014) Identification of GPM6A and GPM6B as potential new human lymphoid leukemia-associated oncogenes. Cell Oncol 37:179–191

    Article  CAS  Google Scholar 

  25. Kaucka M, Plevova K, Pavlova S, Janovska P, Mishra A, Verner J et al (2013) The planar cell polarity pathway drives pathogenesis of chronic lymphocytic leukemia by the regulation of B-lymphocyte migration. Cancer Res 73:1491–1501

    Article  CAS  PubMed  Google Scholar 

  26. Mirkowska P, Hofmann A, Sedek L, Slamova L, Mejstrikova E, Szczepanski T et al (2013) Leukemia surfaceome analysis reveals new disease-associated features. Blood 121:e149–e159

    Article  CAS  PubMed  Google Scholar 

  27. Del Giudice I, Messina M, Chiaretti S, Santangelo S, Tavolaro S, De Propris MS et al (2012) Behind the scenes of non-nodal MCL: downmodulation of genes involved in actin cytoskeleton organization, cell projection, cell adhesion, tumour invasion, TP53 pathway and mutated status of immunoglobulin heavy chain genes. Br J Haematol 156:601–611

    Article  PubMed  CAS  Google Scholar 

  28. Bonardi F, Fusetti F, Deelen P, van Gosliga D, Vellenga E, Schuringa JJ (2013) A proteomics and transcriptomics approach to identify leukemic stem cell (LSC) markers. Mol Cell Proteomics 12:626–637

    Article  CAS  PubMed  Google Scholar 

  29. Wobus M, Bornhauser M, Jacobi A, Krater M, Otto O, Ortlepp C et al (2015) Association of the EGF-TM7 receptor CD97 expression with FLT3-ITD in acute myeloid leukemia. Oncotarget 6:38804–38815

    PubMed  PubMed Central  Google Scholar 

  30. Pabst C, Bergeron A, Lavallee VP, Yeh J, Gendron P, Norddahl GL et al (2016) GPR56 identifies primary human acute myeloid leukemia cells with high repopulating potential in vivo. Blood 27:2018–27

    Article  CAS  Google Scholar 

  31. Hricik T, Federici G, Zeuner A, Alimena G, Tafuri A, Tirelli V et al (2013) Transcriptomic and phospho-proteomic analyzes of erythroblasts expanded in vitro from normal donors and from patients with polycythemia vera. Am J Hematol 88:723–729

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Ke N, Sundaram R, Liu G, Chionis J, Fan W, Rogers C et al (2007) Orphan G protein-coupled receptor GPR56 plays a role in cell transformation and tumorigenesis involving the cell adhesion pathway. Mol Cancer Ther 6:1840–1850

    Article  CAS  PubMed  Google Scholar 

  33. Vallon M, Essler M (2006) Proteolytically processed soluble tumor endothelial marker (TEM) 5 mediates endothelial cell survival during angiogenesis by linking integrin alpha(v)beta3 to glycosaminoglycans. J Biol Chem 281:34179–34188

    Article  CAS  PubMed  Google Scholar 

  34. Masiero M, Simoes FC, Han HD, Snell C, Peterkin T, Bridges E et al (2013) A core human primary tumor angiogenesis signature identifies the endothelial orphan receptor ELTD1 as a key regulator of angiogenesis. Cancer Cell 24:229–241

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Dieterich LC, Mellberg S, Langenkamp E, Zhang L, Zieba A, Salomaki H et al (2012) Transcriptional profiling of human glioblastoma vessels indicates a key role of VEGF-A and TGFbeta2 in vascular abnormalization. J Pathol 228:378–390

    Article  CAS  PubMed  Google Scholar 

  36. Fukushima Y, Oshika Y, Tsuchida T, Tokunaga T, Hatanaka H, Kijima H et al (1998) Brain-specific angiogenesis inhibitor 1 expression is inversely correlated with vascularity and distant metastasis of colorectal cancer. Int J Oncol 13:967–970

    CAS  PubMed  Google Scholar 

  37. Hatanaka H, Oshika Y, Abe Y, Yoshida Y, Hashimoto T, Handa A et al (2000) Vascularization is decreased in pulmonary adenocarcinoma expressing brain-specific angiogenesis inhibitor 1 (BAI1). Int J Mol Med 5:181–183

    CAS  PubMed  Google Scholar 

  38. Hao C, Wang L, Peng S, Cao M, Li H, Hu J et al (2015) Gene mutations in primary tumors and corresponding patient-derived xenografts derived from non-small cell lung cancer. Cancer Lett 357:179–185

    Article  CAS  PubMed  Google Scholar 

  39. Guo R, Wu G, Li H, Qian P, Han J, Pan F et al (2013) Promoter methylation profiles between human lung adenocarcinoma multidrug resistant A549/cisplatin (A549/DDP) cells and its progenitor A549 cells. Biol Pharm Bull 36:1310–1316

    Article  CAS  PubMed  Google Scholar 

  40. Hsu YC, Yuan S, Chen HY, Yu SL, Liu CH, Hsu PY et al (2009) A four-gene signature from NCI-60 cell line for survival prediction in non-small cell lung cancer. Clin Cancer Res 15:7309–7315

    Article  CAS  PubMed  Google Scholar 

  41. Bari MF, Brown H, Nicholson AG, Kerr KM, Gosney JR, Wallace WA et al (2014) BAI3, CDX2 and VIL1: a panel of three antibodies to distinguish small cell from large cell neuroendocrine lung carcinomas. Histopathology 64:547–556

    Article  PubMed  Google Scholar 

  42. Steinert M, Wobus M, Schütz A, Aust G (2002) CD97, but not its closely related EGF-TM7 family member EMR2, is expressed on gastric pancreatic and esophageal carcinomas. Am J Clin Pathol 118(5):699–707

    Article  PubMed  Google Scholar 

  43. Kausar T, Sharma R, Hasan MR, Tripathi SC, Saraya A, Chattopadhyay TK et al (2011) Clinical significance of GPR56, transglutaminase 2, and NF-kappaB in esophageal squamous cell carcinoma. Cancer Invest 29:42–48

    Article  CAS  PubMed  Google Scholar 

  44. Miyamoto N, Yamamoto H, Taniguchi H, Miyamoto C, Oki M, Adachi Y et al (2007) Differential expression of angiogenesis-related genes in human gastric cancers with and those without high-frequency microsatellite instability. Cancer Lett 254:42–53

    Article  CAS  PubMed  Google Scholar 

  45. Miao R, Guo X, Zhi Q, Shi Y, Li L, Mao X et al (2013) VEZT, a novel putative tumor suppressor, suppresses the growth and tumorigenicity of gastric cancer. PLoS One 8:e74409

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Yoshida Y, Oshika Y, Fukushima Y, Tokunaga T, Hatanaka H, Kijima H et al (1999) Expression of angiostatic factors in colorectal cancer. Int J Oncol 15:1221–1225

    CAS  PubMed  Google Scholar 

  47. Katoh M, Katoh M (2007) Comparative integromics on non-canonical WNT or planar cell polarity signaling molecules: transcriptional mechanism of PTK7 in colorectal cancer and that of SEMA6A in undifferentiated ES cells. Int J Mol Med 20:405–409

    CAS  PubMed  Google Scholar 

  48. Steinert M, Wobus M, Boltze C, Schütz A, Wahlbuhl M, Hamann J et al (2002) Expression and regulation of CD97 in colorectal carcinoma cell lines and tumor tissues. Am J Pathol 161:1657–1667

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Galle J, Sittig D, Hanisch I, Wobus M, Wandel E, Loeffler M et al (2006) Individual cell-based models of tumor–environment interactions. Multiple effects of CD97 on tumor invasion. Am J Pathol 169:1802–1811

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Nilsson O (2013) Profiling of ileal carcinoids. Neuroendocrinology 97:7–18

    Article  CAS  PubMed  Google Scholar 

  51. Ammerpohl O, Pratschke J, Schafmayer C, Haake A, Faber W, von Kampen O et al (2012) Distinct DNA methylation patterns in cirrhotic liver and hepatocellular carcinoma. Int J Cancer 130:1319–1328

    Article  CAS  PubMed  Google Scholar 

  52. Tomimaru Y, Koga H, Yano H, de la Monte S, Wands JR, Kim M (2013) Upregulation of T-cell factor-4 isoform-responsive target genes in hepatocellular carcinoma. Liver Int 33:1100–1112

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Wu J, Lei L, Wang S, Gu D, Zhang J (2012) Immunohistochemical expression and prognostic value of CD97 and its ligand CD55 in primary gallbladder carcinoma. J Biomed Biotechnol 2012:587672. doi:10.1155/2012/587672

    PubMed  PubMed Central  Google Scholar 

  54. He Z, Wu H, Jiao Y, Zheng J (2015) Expression and prognostic value of CD97 and its ligand CD55 in pancreatic cancer. Oncol Lett 9:793–797

    PubMed  Google Scholar 

  55. Huang Y, Fan J, Yang J, Zhu GZ (2008) Characterization of GPR56 protein and its suppressed expression in human pancreatic cancer cells. Mol Cell Biochem 308:133–139

    Article  CAS  PubMed  Google Scholar 

  56. Maina EN, Morris MR, Zatyka M, Raval RR, Banks RE, Richards FM et al (2005) Identification of novel VHL target genes and relationship to hypoxic response pathways. Oncogene 24:4549–4558

    Article  CAS  PubMed  Google Scholar 

  57. Ward Y, Lake R, Martin PL, Killian K, Salerno P, Wang T et al (2013) CD97 amplifies LPA receptor signaling and promotes thyroid cancer progression in a mouse model. Oncogene 32:2726–2738

    Article  CAS  PubMed  Google Scholar 

  58. Ward Y, Lake R, Yin JJ, Heger CD, Raffeld M, Goldsmith PK et al (2011) LPA receptor heterodimerizes with CD97 to amplify LPA-initiated RHO-dependent signaling and invasion in prostate cancer cells. Cancer Res 71:7301–7311

    Article  CAS  PubMed  Google Scholar 

  59. White GR, Varley JM, Heighway J (1998) Isolation and characterization of a human homologue of the latrophilin gene from a region of 1p31.1 implicated in breast cancer. Oncogene 17:3513–3519

    Article  CAS  PubMed  Google Scholar 

  60. Yang L, Friedland S, Corson N, Xu L (2014) GPR56 inhibits melanoma growth by internalizing and degrading its ligand TG2. Cancer Res 74:1–10

    CAS  Google Scholar 

  61. Yang L, Chen G, Mohanty S, Scott G, Fazal F, Rahman A et al (2011) GPR56 regulates VEGF production and angiogenesis during melanoma progression. Cancer Res 71:5558–5568

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Meisen WH, Dubin S, Sizemore ST, Mathsyaraja H, Thies K, Lehman NL et al (2015) Changes in BAI1 and nestin expression are prognostic indicators for survival and metastases in breast cancer and provide opportunities for dual targeted therapies. Mol Cancer Ther 14:307–314

    Article  CAS  PubMed  Google Scholar 

  63. Liao S, Desouki MM, Gaile DP, Shepherd L, Nowak NJ, Conroy J et al (2012) Differential copy number aberrations in novel candidate genes associated with progression from in situ to invasive ductal carcinoma of the breast. Genes Chromosomes Cancer 51:1067–1078

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Davies JQ, Lin HH, Stacey M, Yona S, Chang GW, Gordon S et al (2011) Leukocyte adhesion-GPCR EMR2 is aberrantly expressed in human breast carcinomas and is associated with patient survival. Oncol Rep 25:619–627

    CAS  PubMed  Google Scholar 

  65. Tang X, Jin R, Qu G, Wang X, Li Z, Yuan Z et al (2013) GPR116, an adhesion G-protein-coupled receptor, promotes breast cancer metastasis via the Galphaq-p63RhoGEF-Rho GTPase pathway. Cancer Res 73:6206–6218

    Article  CAS  PubMed  Google Scholar 

  66. Zyryanova T, Schneider R, Adams V, Sittig D, Kerner C, Gebhardt C et al (2014) Skeletal muscle expression of the adhesion-GPCR CD97: CD97 deletion induces an abnormal structure of the sarcoplasmatic reticulum but does not impair skeletal muscle function. PLoS One 9, e100513

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  67. Aust G, Wandel E, Boltze C, Sittig D, Schütz A, Horn LC et al (2006) Diversity of CD97 in smooth muscle cells (SMCs). Cell Tissue Res 323:1–9

    Article  Google Scholar 

  68. Richter GH, Fasan A, Hauer K, Grunewald TG, Berns C, Rossler S et al (2013) G-Protein coupled receptor 64 promotes invasiveness and metastasis in Ewing sarcomas through PGF and MMP1. J Pathol 230:70–81

    Article  CAS  PubMed  Google Scholar 

  69. Kaur B, Brat DJ, Devi NS, Van Meir EG (2005) Vasculostatin, a proteolytic fragment of brain angiogenesis inhibitor 1, is an antiangiogenic and antitumorigenic factor. Oncogene 24:3632–3642

    Article  CAS  PubMed  Google Scholar 

  70. Kaur B, Cork SM, Sandberg EM, Devi NS, Zhang Z, Klenotic PA et al (2009) Vasculostatin inhibits intracranial glioma growth and negatively regulates in vivo angiogenesis through a CD36-dependent mechanism. Cancer Res 69:1212–1220

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Cork SM, Kaur B, Devi NS, Cooper L, Saltz JH, Sandberg EM et al (2012) A proprotein convertase/MMP-14 proteolytic cascade releases a novel 40 kDa vasculostatin from tumor suppressor BAI1. Oncogene 31:5144–5152

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Zhu D, Hunter SB, Vertino PM, Van Meir EG (2011) Overexpression of MBD2 in glioblastoma maintains epigenetic silencing and inhibits the antiangiogenic function of the tumor suppressor gene BAI1. Cancer Res 71:5859–5870

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Kaur B, Brat DJ, Calkins CC, Van Meir EG (2003) Brain angiogenesis inhibitor 1 is differentially expressed in normal brain and glioblastoma independently of p53 expression. Am J Pathol 162:19–27

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Ivan ME, Safaee M, Oh T, Clark AJ, Sun MZ, Kim J et al (2015) Epidermal growth factor-like module containing mucin-like hormone receptor 2 expression in gliomas. J Neurooncol 121:53–61

    Article  CAS  PubMed  Google Scholar 

  75. Rutkowski MJ, Sughrue ME, Kane AJ, Kim JM, Bloch O, Parsa AT (2011) Epidermal growth factor module-containing mucin-like receptor 2 is a newly identified adhesion G protein-coupled receptor associated with poor overall survival and an invasive phenotype in glioblastoma. J Neurooncol 105:165–171

    Article  CAS  PubMed  Google Scholar 

  76. Kane AJ, Sughrue ME, Rutkowski MJ, Phillips JJ, Parsa AT (2010) EMR-3: a potential mediator of invasive phenotypic variation in glioblastoma and novel therapeutic target. Neuroreport 21:1018–1022

    Article  CAS  PubMed  Google Scholar 

  77. Safaee M, Clark AJ, Oh MC, Ivan ME, Bloch O, Kaur G et al (2013) Overexpression of CD97 confers an invasive phenotype in glioblastoma cells and is associated with decreased survival of glioblastoma patients. PLoS One 8(4), e62765. doi:10.1371/journal.pone.0062765

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  78. Liu JK, Lubelski D, Schonberg DL, Wu Q, Hale JS, Flavahan WA et al (2014) Phage display discovery of novel molecular targets in glioblastoma-initiating cells. Cell Death Differ 21:1325–1339

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Safaee M, Fakurnejad S, Bloch O, Clark AJ, Ivan ME, Sun MZ et al (2015) Proportional upregulation of CD97 isoforms in glioblastoma and glioblastoma-derived brain tumor initiating cells. PLoS One 10, e0111532

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  80. Chidambaram A, Fillmore HL, Van Meter TE, Dumur CI, Broaddus WC (2012) Novel report of expression and function of CD97 in malignant gliomas: correlation with Wilms tumor 1 expression and glioma cell invasiveness. J Neurosurg 116:843–853

    Article  CAS  PubMed  Google Scholar 

  81. Somasundaram A, Ardanowski N, Opalak CF, Fillmore HL, Chidambaram A, Broaddus WC (2014) Wilms tumor 1 gene, CD97, and the emerging biogenetic profile of glioblastoma. Neurosurg Focus 37:E14

    Article  PubMed  Google Scholar 

  82. Shashidhar S, Lorente G, Nagavarapu U, Nelson A, Kuo J, Cummins J et al (2005) GPR56 is a GPCR that is overexpressed in gliomas and functions in tumor cell adhesion. Oncogene 24:1673–1682

    Article  CAS  PubMed  Google Scholar 

  83. Taatjes DJ (2010) The human Mediator complex: a versatile, genome-wide regulator of transcription. Trends Biochem Sci 35:315–322

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Towner RA, Jensen RL, Colman H, Vaillant B, Smith N, Casteel R et al (2013) ELTD1, a potential new biomarker for gliomas. Neurosurgery 72:77–90

    Article  PubMed  PubMed Central  Google Scholar 

  85. Cork SM, Van Meir EG (2011) Emerging roles for the BAI1 protein family in the regulation of phagocytosis, synaptogenesis, neurovasculature, and tumor development. J Mol Med (Berl) 89:743–752

    Article  CAS  Google Scholar 

  86. Fujii K, Kurozumi K, Ichikawa T, Onishi M, Shimazu Y, Ishida J et al (2013) The integrin inhibitor cilengitide enhances the anti-glioma efficacy of vasculostatin-expressing oncolytic virus. Cancer Gene Ther 20:437–444

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Whittier KL, Boese EA, Gibson-Corley KN, Kirby PA, Darbro BW, Qian Q et al (2013) G-protein coupled receptor expression patterns delineate medulloblastoma subgroups. Acta Neuropathol Commun 1:66

    Article  PubMed  PubMed Central  Google Scholar 

  88. Boligan KF, Mesa C, Fernandez LE, von Gunten S (2015) Cancer intelligence acquired (CIA): tumor glycosylation and sialylation codes dismantling antitumor defense. Cell Mol Life Sci 72:1231–1248

    Article  CAS  PubMed  Google Scholar 

  89. Pinho SS, Reis CA (2015) Glycosylation in cancer: mechanisms and clinical implications. Nat Rev Cancer 15:540–555

    Article  CAS  PubMed  Google Scholar 

  90. Durrant LG, Chapman MA, Buckley DJ, Spendlove I, Robins RA, Armitage NC (2003) Enhanced expression of the complement regulatory protein CD55 predicts a poor prognosis in colorectal cancer patients. Cancer Immunol Immunother 52:638–642

    Article  CAS  PubMed  Google Scholar 

  91. Liu Y, Chen L, Peng S, Chen Z, Gimm O, Finke R et al (2005) The expression of CD97EGF and its ligand CD55 on marginal epithelium is related to higher stage and depth of tumor invasion of gastric carcinomas. Oncol Rep 14:1413–1420

    CAS  PubMed  Google Scholar 

  92. Loberg RD, Wojno KJ, Day LL, Pienta KJ (2005) Analysis of membrane-bound complement regulatory proteins in prostate cancer. Urology 66:1321–1326

    Article  PubMed  Google Scholar 

  93. Han SL, Xu C, Wu XL, Li JL, Liu Z, Zeng QQ (2010) The impact of expressions of CD97 and its ligand CD55 at the invasion front on prognosis of rectal adenocarcinoma. Int J Colorectal Dis 25:695–702

    Article  PubMed  Google Scholar 

  94. Park D, Tosello-Trampont AC, Elliott MR, Lu M, Haney LB, Ma Z et al (2007) BAI1 is an engulfment receptor for apoptotic cells upstream of the ELMO/Dock180/Rac module. Nature 450:430–434

    Article  CAS  PubMed  Google Scholar 

  95. Okajima D, Kudo G, Yokota H (2010) Brain-specific angiogenesis inhibitor 2 (BAI2) may be activated by proteolytic processing. J Recept Signal Transduct Res 30:143–153

    Article  CAS  PubMed  Google Scholar 

  96. Gray JX, Haino M, Roth MJ, Maguire JE, Jensen PN, Yarme A et al (1996) CD97 is a processed, seven-transmembrane, heterodimeric receptor associated with inflammation. J Immunol 157:5438–5447

    CAS  PubMed  Google Scholar 

  97. Abe J, Fukuzawa T, Hirose S (2002) Cleavage of Ig-Hepta at a “SEA” module and at a conserved G protein-coupled receptor proteolytic site. J Biol Chem 277:23391–23398

    Article  CAS  PubMed  Google Scholar 

  98. Moriguchi T, Haraguchi K, Ueda N, Okada M, Furuya T, Akiyama T (2004) DREG, a developmentally regulated G protein-coupled receptor containing two conserved proteolytic cleavage sites. Genes Cells 9:549–560

    Article  CAS  PubMed  Google Scholar 

  99. Krasnoperov V, Deyev IE, Serova OV, Xu C, Lu Y, Buryanovsky L et al (2009) Dissociation of the subunits of the calcium-independent receptor of alpha-latrotoxin as a result of two-step proteolysis. Biochemistry 48:3230–3238

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Wang T, Ward Y, Tian L, Lake R, Guedez L, Stetler-Stevenson WG et al (2004) CD97, an adhesion receptor on inflammatory cells, stimulates angiogenesis through binding integrin counter receptors on endothelial cells. Blood 105:2836–2844

    Article  PubMed  CAS  Google Scholar 

  101. Hamann J, Wishaupt JO, van Lier RA, Smeets TJ, Breedveld FC, Tak PP (1999) Expression of the activation antigen CD97 and its ligand CD55 in rheumatoid synovial tissue. Arthritis Rheum 42:650–658

    Article  CAS  PubMed  Google Scholar 

  102. de Groot DM, Vogel G, Dulos J, Teeuwen L, Stebbins K, Hamann J et al (2009) Therapeutic antibody targeting of CD97 in experimental arthritis: the role of antigen expression, shedding, and internalization on the pharmacokinetics of anti-CD97 monoclonal antibody 1B2. J Immunol 183:4127–4134

    Article  PubMed  Google Scholar 

  103. Dai S, Wang X, Li X, Cao Y (2015) MicroRNA-139-5p acts as a tumor suppressor by targeting ELTD1 and regulating cell cycle in glioblastoma multiforme. Biochem Biophys Res Commun 467:204–210

    Article  CAS  PubMed  Google Scholar 

  104. Hsiao CC, Keysselt K, Chen HY, Sittig D, Hamann J, Lin HH et al (2015) The Adhesion GPCR CD97 inhibits apoptosis. Int J Biochem Cell Biol 65:197–208

    Article  CAS  PubMed  Google Scholar 

  105. Xu L, Begum S, Hearn JD, Hynes RO (2006) GPR56, an atypical G protein-coupled receptor, binds tissue transglutaminase, TG2, and inhibits melanoma tumor growth and metastasis. Proc Natl Acad Sci U S A 103:9023–9028

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Fu JF, Yen TH, Chen Y, Huang YJ, Hsu CL, Liang DC et al (2013) Involvement of Gpr125 in the myeloid sarcoma formation induced by cooperating MLL/AF10(OM-LZ) and oncogenic KRAS in a mouse bone marrow transplantation model. Int J Cancer 133:1792–1802

    Article  CAS  PubMed  Google Scholar 

  107. Mouw JK, Ou G, Weaver VM (2014) Extracellular matrix assembly: a multiscale deconstruction. Nat Rev Mol Cell Biol 15:771–785

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Luo R, Jin Z, Deng Y, Strokes N, Piao X (2012) Disease-associated mutations prevent GPR56-collagen III interaction. PLoS One 1, e29818. doi:10.1371/journal.pone.0029818

    Article  CAS  Google Scholar 

  109. Koirala S, Jin Z, Piao X, Corfas G (2009) GPR56-regulated granule cell adhesion is essential for rostral cerebellar development. J Neurosci 29:7439–7449

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Stacey M, Chang GW, Davies JQ, Kwakkenbos MJ, Sanderson RD, Hamann J et al (2003) The epidermal growth factor-like domains of the human EMR2 receptor mediate cell attachment through chondroitin sulphate glycosaminoglycans. Blood 102:2916–2924

    Article  CAS  PubMed  Google Scholar 

  111. Paavola KJ, Sidik H, Zuchero JB, Eckart M, Talbot WS (2014) Type IV collagen is an activating ligand for the adhesion G protein-coupled receptor GPR126. Sci Signal 7(338):ra76. doi:10.1126/scisignal.2005347

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  112. Petersen SC, Luo R, Liebscher I, Giera S, Jeong SJ, Mogha A et al (2015) The adhesion GPCR GPR126 has distinct, domain-dependent functions in Schwann cell development mediated by interaction with laminin-211. Neuron 85:755–769

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Strutt D, Schnabel R, Fiedler F, Prömel S (2016) Adhesion GPCRs govern polarity of epithelia and cell migration. In: Langenhan T, Schöneberg T (eds) Adhesion G protein-coupled receptors: molecular, physiological and pharmacological principles in health and disease. Springer, Heidelberg

    Google Scholar 

  114. Hsiao CC, Wang WC, Kuo WL, Chen HY, Chen TC, Hamann J et al (2014) CD97 inhibits cell migration in human fibrosarcoma cell by modulating TIMP-2/MT1-MMP/MMP-2 activity. FEBS J 281:4878–4891

    Article  CAS  PubMed  Google Scholar 

  115. Musa G, Engel FB, Niaudet C (2016) Heart development, angiogenesis and blood-brain barrier function is modulated by adhesion GPCRs. In: Langenhan T, Schöneberg T (eds) Adhesion G protein-coupled receptors: molecular, physiological and pharmacological principles in health and disease. Springer, Heidelberg

    Google Scholar 

  116. Nishimori H, Shiratsuchi T, Urano T, Kimura Y, Kiyono K, Tatsumi K et al (1997) A novel brain-specific p53-target gene, BAI1, containing thrombospondin type 1 repeats inhibits experimental angiogenesis. Oncogene 15:2145–2150

    Article  CAS  PubMed  Google Scholar 

  117. Kang X, Xiao X, Harata M, Bai Y, Nakazaki Y, Soda Y et al (2006) Antiangiogenic activity of BAI1 in vivo: implications for gene therapy of human glioblastomas. Cancer Gene Ther 13:385–392

    Article  CAS  PubMed  Google Scholar 

  118. Lee JH, Koh JT, Shin BA, Ahn KY, Roh JH, Kim YJ et al (2001) Comparative study of angiostatic and anti-invasive gene expressions as prognostic factors in gastric cancer. Int J Oncol 18:355–361

    CAS  PubMed  Google Scholar 

  119. Kudo S, Konda R, Obara W, Kudo D, Tani K, Nakamura Y et al (2007) Inhibition of tumor growth through suppression of angiogenesis by brain-specific angiogenesis inhibitor 1 gene transfer in murine renal cell carcinoma. Oncol Rep 18:785–791

    CAS  PubMed  Google Scholar 

  120. de Fraipont F, Nicholson AC, Feige JJ, Van Meir EG (2001) Thrombospondins and tumor angiogenesis. Trends Mol Med 7:401–407

    Article  PubMed  Google Scholar 

  121. Nicholson AC, Malik SB, Logsdon JM Jr, Van Meir EG (2005) Functional evolution of ADAMTS genes: evidence from analyses of phylogeny and gene organization. BMC Evol Biol 5:11

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  122. Pleasance ED, Cheetham RK, Stephens PJ, McBride DJ, Humphray SJ, Greenman CD et al (2010) A comprehensive catalogue of somatic mutations from a human cancer genome. Nature 463:191–196

    Article  CAS  PubMed  Google Scholar 

  123. Arac D, Boucard AA, Bolliger MF, Nguyen J, Soltis SM, Sudhof TC et al (2012) A novel evolutionarily conserved domain of cell-adhesion GPCRs mediates autoproteolysis. EMBO J 31:1364–1378

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Zhu D, Van Meir EG (2016) BAI1: from cancer to neurological disease. Oncotarget

    Google Scholar 

  125. St Croix B, Rago C, Velculescu V, Traverso G, Romans KE, Montgomery E et al (2000) Genes expressed in human tumor endothelium. Science 289:1197–1202

    Article  CAS  PubMed  Google Scholar 

  126. Carson-Walter EB, Watkins DN, Nanda A, Vogelstein B, Kinzler KW, St CB (2001) Cell surface tumor endothelial markers are conserved in mice and humans. Cancer Res 61:6649–6655

    CAS  PubMed  Google Scholar 

  127. Gao Y, Fan X, Li W, Ping W, Deng Y, Fu X (2014) miR-138-5p reverses gefitinib resistance in non-small cell lung cancer cells via negatively regulating G protein-coupled receptor 124. Biochem Biophys Res Commun 446:179–186

    Article  CAS  PubMed  Google Scholar 

  128. Shiratsuchi T, Nishimori H, Ichise H, Nakamura Y, Tokino T (1997) Cloning and characterization of BAI2 and BAI3, novel genes homologous to brain-specific angiogenesis inhibitor 1 (BAI1). Cytogenet Cell Genet 79:103–108

    Article  CAS  PubMed  Google Scholar 

  129. Koh JT, Kook H, Kee HJ, Seo YW, Jeong BC, Lee JH et al (2004) Extracellular fragment of brain-specific angiogenesis inhibitor 1 suppresses endothelial cell proliferation by blocking alphavbeta5 integrin. Exp Cell Res 294:172–184

    Article  CAS  PubMed  Google Scholar 

  130. Klenotic PA, Huang P, Palomo J, Kaur B, Van Meir EG, Vogelbaum MA et al (2010) Histidine-rich glycoprotein modulates the anti-angiogenic effects of vasculostatin. Am J Pathol 176:2039–2050

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Shiratsuchi T, Futamura M, Oda K, Nishimori H, Nakamura Y, Tokino T (1998) Cloning and characterization of BAI-associated protein 1: a PDZ domain-containing protein that interacts with BAI1. Biochem Biophys Res Commun 247:597–604

    Article  CAS  PubMed  Google Scholar 

  132. Stephenson JR, Paavola KJ, Schaefer SA, Kaur B, Van Meir EG, Hall RA (2013) Brain-specific angiogenesis inhibitor-1 signaling, regulation, and enrichment in the postsynaptic density. J Biol Chem 288:22248–22256

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Oda K, Shiratsuchi T, Nishimori H, Inazawa J, Yoshikawa H, Taketani Y et al (1999) Identification of BAIAP2 (BAI-associated protein 2), a novel human homologue of hamster IRSp53, whose SH3 domain interacts with the cytoplasmic domain of BAI1. Cytogenet Cell Genet 84:75–82

    Article  CAS  PubMed  Google Scholar 

  134. Kim JC, Kim SY, Roh SA, Cho DH, Kim DD, Kim JH et al (2008) Gene expression profiling: canonical molecular changes and clinicopathological features in sporadic colorectal cancers. World J Gastroenterol 14:6662–6672

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Wang Q (2015) Identification of biomarkers for metastatic osteosarcoma based on DNA microarray data. Neoplasma 62:365–371

    Article  CAS  PubMed  Google Scholar 

  136. Aust G, Hamann J, Schilling N, Wobus M (2003) Detection of alternatively spliced EMR2 mRNAs in colorectal tumor cell lines but rare expression of the molecule in the corresponding adenocarcinomas. Virchows Arch 443:32–37

    Article  CAS  PubMed  Google Scholar 

  137. Grone J, Lenze D, Jurinovic V, Hummel M, Seidel H, Leder G et al (2011) Molecular profiles and clinical outcome of stage UICC II colon cancer patients. Int J Colorectal Dis 26:847–858

    Article  PubMed  Google Scholar 

  138. Liu D, Trojanowicz B, Ye L, Li C, Zhang L, Li X et al (2012) The invasion and metastasis promotion role of CD97 small isoform in gastric carcinoma. PLoS One 7, e39989

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Boltze C, Schneider-Stock R, Aust G, Mawrin C, Dralle H, Roessner A et al (2002) CD97, CD95 and Fas-L clearly discriminate between chronic pancreatitis and pancreatic ductal adenocarcinoma in perioperative evaluation of cryocut sections. Pathol Int 52:83–88

    Article  CAS  PubMed  Google Scholar 

  140. Singh V, Singh LC, Vasudevan M, Chattopadhyay I, Borthakar BB, Rai AK et al (2015) Esophageal cancer epigenomics and integrome analysis of genome-wide methylation and expression in high risk northeast Indian population. OMICS 19:688–699

    Article  CAS  PubMed  Google Scholar 

  141. Lu YY, Sweredoski MJ, Huss D, Lansford R, Hess S, Tirrell DA (2013) Prometastatic GPCR CD97 is a direct target of tumor suppressor microRNA-126. ACS Chem Biol 9:334–338

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  142. Hamann J, Vogel B, van Schijndel GM, van Lier RA (1996) The seven-span transmembrane receptor CD97 has a cellular ligand (CD55, DAF). J Exp Med 184:1185–1189

    Article  CAS  PubMed  Google Scholar 

  143. Wandel E, Saalbach A, Sittig D, Gebhardt C, Aust G (2012) Thy-1 (CD90) is an interaction partner for CD97 on activated endothelial cells. J Immunol 188:1442–1450

    Article  CAS  PubMed  Google Scholar 

  144. Fukuzawa T, Ishida J, Kato A, Ichinose T, Ariestanti DM, Takahashi T et al (2013) Lung surfactant levels are regulated by Ig-Hepta/GPR116 by monitoring surfactant protein D. PLoS One 8, e69451

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Yang MY, Hilton MB, Seaman S, Haines DC, Nagashima K, Burks CM et al (2013) Essential regulation of lung surfactant homeostasis by the orphan G protein-coupled receptor GPR116. Cell Rep 3:1457–64

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  146. Bridges JP, Ludwig MG, Mueller M, Kinzel B, Sato A, Xu Y et al (2013) Orphan G protein-coupled receptor GPR116 regulates pulmonary surfactant pool size. Am J Respir Cell Mol Biol 49:348–57

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  147. Yang L, Xu L (2012) GPR56 in cancer progression: current status and future perspective. Future Oncol 8:431–440

    Article  CAS  PubMed  Google Scholar 

  148. Mori A, Arii S, Furutani M, Hanaki K, Takeda Y, Moriga T et al (1999) Vascular endothelial growth factor-induced tumor angiogenesis and tumorigenicity in relation to metastasis in a HT1080 human fibrosarcoma cell model. Int J Cancer 80:738–743

    Article  CAS  PubMed  Google Scholar 

  149. Duda DG, Sunamura M, Lozonschi L, Yokoyama T, Yatsuoka T, Motoi F et al (2002) Overexpression of the p53-inducible brain-specific angiogenesis inhibitor 1 suppresses efficiently tumour angiogenesis. Br J Cancer 86:490–496

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Peeters MC, Fokkelman M, Boogaard B, Egerod KL, van de Water B, Ijzerman AP et al (2015) The adhesion G protein-coupled receptor G2 (ADGRG2/GPR64) constitutively activates SRE and NFkappaB and is involved in cell adhesion and migration. Cell Signal 27:2579–2588

    Article  CAS  PubMed  Google Scholar 

  151. Leja J, Essaghir A, Essand M, Wester K, Oberg K, Totterman TH et al (2009) Novel markers for enterochromaffin cells and gastrointestinal neuroendocrine carcinomas. Mod Pathol 22:261–272

    Article  CAS  PubMed  Google Scholar 

  152. White GR, Varley JM, Heighway J (2000) Genomic structure and expression profile of LPHH1, a 7TM gene variably expressed in breast cancer cell lines. Biochim Biophys Acta 1491:75–92

    Article  CAS  PubMed  Google Scholar 

  153. Zhang S, Liu Y, Liu Z, Zhang C, Cao H, Ye Y et al (2014) Transcriptome profiling of a multiple recurrent muscle-invasive urothelial carcinoma of the bladder by deep sequencing. PLoS One 9, e91466

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  154. Wang Y, Fan X, Zhang W, Zhang C, Wang J, Jiang T et al (2015) Deficiency of very large G-protein-coupled receptor-1 is a risk factor of tumor-related epilepsy: a whole transcriptome sequencing analysis. J Neurooncol 121:609–616

    Article  CAS  PubMed  Google Scholar 

  155. Mosmann TR, Li L, Sad S (1997) Functions of CD8 T-cell subsets secreting different cytokine patterns. Semin Immunol 9:87–92

    Article  CAS  PubMed  Google Scholar 

  156. Nam DH, Park K, Suh YL, Kim JH (2004) Expression of VEGF and brain specific angiogenesis inhibitor-1 in glioblastoma: prognostic significance. Oncol Rep 11:863–869

    CAS  PubMed  Google Scholar 

  157. Yoon KC, Ahn KY, Lee JH, Chun BJ, Park SW, Seo MS et al (2005) Lipid-mediated delivery of brain-specific angiogenesis inhibitor 1 gene reduces corneal neovascularization in an in vivo rabbit model. Gene Ther 12:617–624

    Article  CAS  PubMed  Google Scholar 

  158. Slack A, Bovenzi V, Bigey P, Ivanov MA, Ramchandani S, Bhattacharya S et al (2002) Antisense MBD2 gene therapy inhibits tumorigenesis. J Gene Med 4:381–389

    Article  CAS  PubMed  Google Scholar 

  159. Campbell PM, Bovenzi V, Szyf M (2004) Methylated DNA-binding protein 2 antisense inhibitors suppress tumourigenesis of human cancer cell lines in vitro and in vivo. Carcinogenesis 25:499–507

    Article  CAS  PubMed  Google Scholar 

Download references

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.

Author information

Authors and Affiliations

  1. Department of Surgery, Research Laboratories, University of Leipzig, Liebigstraße 19, Leipzig, 04103, Germany

    Gabriela Aust

  2. Department of Neurosurgery and Hematology & Medical Oncology, School of Medicine and Winship Cancer Institute, Emory University, Atlanta, GA, 30322, USA

    Dan Zhu & Erwin G. Van Meir

  3. Department of Biomedical Genetics, University of Rochester Medical Center, Rochester, NY, 14642, USA

    Lei Xu

Authors
  1. Gabriela Aust
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dan Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Erwin G. Van Meir
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lei Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gabriela Aust .

Editor information

Editors and Affiliations

  1. Institute of Physiology Department of Neurophysiology, University of Würzburg, Würzburg, Germany

    Tobias Langenhan

  2. Institute of Biochemistry Medical Faculty, University of Leipzig, Leipzig, Germany

    Torsten Schöneberg

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing AG

About this chapter

Cite this chapter

Aust, G., Zhu, D., Van Meir, E.G., Xu, L. (2016). Adhesion GPCRs in Tumorigenesis. In: Langenhan, T., Schöneberg, T. (eds) Adhesion G Protein-coupled Receptors. Handbook of Experimental Pharmacology, vol 234. Springer, Cham. https://doi.org/10.1007/978-3-319-41523-9_17

Download citation

Publish with us

Policies and ethics

Search

Navigation