Adhesion GPCRs in Tumorigenesis

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

Graphical 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.


Tumor cell migration Tumor invasion Metastasis Tumor angiogenesis Tumor therapy 



Cancer Cell Line Encyclopedia


C-terminal fragment


Extracellular domain


Extracellular matrix


GPCR autoproteolysis inducing


GPCR-proteolytic site


N-terminal fragment


Tissue transglutaminase


Thrombospondin repeat



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.


  1. 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, HeidelbergGoogle Scholar
  2. 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, HeidelbergGoogle Scholar
  3. 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, HeidelbergGoogle Scholar
  4. 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, HeidelbergGoogle Scholar
  5. 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, HeidelbergGoogle Scholar
  6. 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 PubMedCrossRefGoogle Scholar
  7. 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 9:2018–2026PubMedPubMedCentralCrossRefGoogle Scholar
  8. 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, HeidelbergGoogle Scholar
  9. 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, HeidelbergGoogle Scholar
  10. 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, HeidelbergGoogle Scholar
  11. 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 483:603–607PubMedPubMedCentralCrossRefGoogle Scholar
  12. 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 2:401–404PubMedCrossRefGoogle Scholar
  13. 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 PubMedPubMedCentralCrossRefGoogle Scholar
  14. 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 PubMedCrossRefGoogle Scholar
  15. 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 PubMedPubMedCentralCrossRefGoogle Scholar
  16. 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 57:1798–1806PubMedGoogle Scholar
  17. 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 446:292–298PubMedCrossRefGoogle Scholar
  18. 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 74:425–441PubMedCrossRefGoogle Scholar
  19. 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 117:6267–6276PubMedPubMedCentralCrossRefGoogle Scholar
  20. 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 43:684–694PubMedCrossRefGoogle Scholar
  21. 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 466:869–873PubMedCrossRefGoogle Scholar
  22. 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 27:1637–1649PubMedCrossRefGoogle Scholar
  23. 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 54:310–314PubMedCrossRefGoogle Scholar
  24. 24.
    Charfi C, Edouard E, Rassart E (2014) Identification of GPM6A and GPM6B as potential new human lymphoid leukemia-associated oncogenes. Cell Oncol 37:179–191CrossRefGoogle Scholar
  25. 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 73:1491–1501PubMedCrossRefGoogle Scholar
  26. 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–e159PubMedCrossRefGoogle Scholar
  27. 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 156:601–611PubMedCrossRefGoogle Scholar
  28. 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 12:626–637PubMedCrossRefGoogle Scholar
  29. 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 6:38804–38815PubMedPubMedCentralGoogle Scholar
  30. 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 27:2018–27CrossRefGoogle Scholar
  31. 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 88:723–729PubMedPubMedCentralCrossRefGoogle Scholar
  32. 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 6:1840–1850PubMedCrossRefGoogle Scholar
  33. 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 281:34179–34188PubMedCrossRefGoogle Scholar
  34. 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 24:229–241PubMedPubMedCentralCrossRefGoogle Scholar
  35. 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 228:378–390PubMedCrossRefGoogle Scholar
  36. 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 13:967–970PubMedGoogle Scholar
  37. 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 5:181–183PubMedGoogle Scholar
  38. 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 357:179–185PubMedCrossRefGoogle Scholar
  39. 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 36:1310–1316PubMedCrossRefGoogle Scholar
  40. 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 15:7309–7315PubMedCrossRefGoogle Scholar
  41. 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 64:547–556PubMedCrossRefGoogle Scholar
  42. 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):699–707PubMedCrossRefGoogle Scholar
  43. 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 29:42–48PubMedCrossRefGoogle Scholar
  44. 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 254:42–53PubMedCrossRefGoogle Scholar
  45. 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:e74409PubMedPubMedCentralCrossRefGoogle Scholar
  46. 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 15:1221–1225PubMedGoogle Scholar
  47. 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 20:405–409PubMedGoogle Scholar
  48. 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 161:1657–1667PubMedPubMedCentralCrossRefGoogle Scholar
  49. 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 169:1802–1811PubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    Nilsson O (2013) Profiling of ileal carcinoids. Neuroendocrinology 97:7–18PubMedCrossRefGoogle Scholar
  51. 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 130:1319–1328PubMedCrossRefGoogle Scholar
  52. 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 33:1100–1112PubMedPubMedCentralCrossRefGoogle Scholar
  53. 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 PubMedPubMedCentralGoogle Scholar
  54. 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 9:793–797PubMedGoogle Scholar
  55. 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 308:133–139PubMedCrossRefGoogle Scholar
  56. 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 24:4549–4558PubMedCrossRefGoogle Scholar
  57. 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 32:2726–2738PubMedCrossRefGoogle Scholar
  58. 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 71:7301–7311PubMedCrossRefGoogle Scholar
  59. 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 17:3513–3519PubMedCrossRefGoogle Scholar
  60. 60.
    Yang L, Friedland S, Corson N, Xu L (2014) GPR56 inhibits melanoma growth by internalizing and degrading its ligand TG2. Cancer Res 74:1–10Google Scholar
  61. 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 71:5558–5568PubMedPubMedCentralCrossRefGoogle Scholar
  62. 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 14:307–314PubMedCrossRefGoogle Scholar
  63. 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 51:1067–1078PubMedPubMedCentralCrossRefGoogle Scholar
  64. 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 25:619–627PubMedGoogle Scholar
  65. 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 73:6206–6218PubMedCrossRefGoogle Scholar
  66. 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, e100513PubMedPubMedCentralCrossRefGoogle Scholar
  67. 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 323:1–9CrossRefGoogle Scholar
  68. 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 230:70–81PubMedCrossRefGoogle Scholar
  69. 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 24:3632–3642PubMedCrossRefGoogle Scholar
  70. 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 69:1212–1220PubMedPubMedCentralCrossRefGoogle Scholar
  71. 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 31:5144–5152PubMedPubMedCentralCrossRefGoogle Scholar
  72. 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 71:5859–5870PubMedPubMedCentralCrossRefGoogle Scholar
  73. 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 162:19–27PubMedPubMedCentralCrossRefGoogle Scholar
  74. 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 121:53–61PubMedCrossRefGoogle Scholar
  75. 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 105:165–171PubMedCrossRefGoogle Scholar
  76. 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 21:1018–1022PubMedCrossRefGoogle Scholar
  77. 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 PubMedPubMedCentralCrossRefGoogle Scholar
  78. 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 21:1325–1339PubMedPubMedCentralCrossRefGoogle Scholar
  79. 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, e0111532PubMedPubMedCentralCrossRefGoogle Scholar
  80. 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 116:843–853PubMedCrossRefGoogle Scholar
  81. 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:E14PubMedCrossRefGoogle Scholar
  82. 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 24:1673–1682PubMedCrossRefGoogle Scholar
  83. 83.
    Taatjes DJ (2010) The human Mediator complex: a versatile, genome-wide regulator of transcription. Trends Biochem Sci 35:315–322PubMedPubMedCentralCrossRefGoogle Scholar
  84. 84.
    Towner RA, Jensen RL, Colman H, Vaillant B, Smith N, Casteel R et al (2013) ELTD1, a potential new biomarker for gliomas. Neurosurgery 72:77–90PubMedPubMedCentralCrossRefGoogle Scholar
  85. 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) 89:743–752CrossRefGoogle Scholar
  86. 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 20:437–444PubMedPubMedCentralCrossRefGoogle Scholar
  87. 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 1:66PubMedPubMedCentralCrossRefGoogle Scholar
  88. 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 72:1231–1248PubMedCrossRefGoogle Scholar
  89. 89.
    Pinho SS, Reis CA (2015) Glycosylation in cancer: mechanisms and clinical implications. Nat Rev Cancer 15:540–555PubMedCrossRefGoogle Scholar
  90. 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 52:638–642PubMedCrossRefGoogle Scholar
  91. 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 14:1413–1420PubMedGoogle Scholar
  92. 92.
    Loberg RD, Wojno KJ, Day LL, Pienta KJ (2005) Analysis of membrane-bound complement regulatory proteins in prostate cancer. Urology 66:1321–1326PubMedCrossRefGoogle Scholar
  93. 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 25:695–702PubMedCrossRefGoogle Scholar
  94. 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 450:430–434PubMedCrossRefGoogle Scholar
  95. 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 30:143–153PubMedCrossRefGoogle Scholar
  96. 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 157:5438–5447PubMedGoogle Scholar
  97. 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 277:23391–23398PubMedCrossRefGoogle Scholar
  98. 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 9:549–560PubMedCrossRefGoogle Scholar
  99. 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 48:3230–3238PubMedPubMedCentralCrossRefGoogle Scholar
  100. 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 105:2836–2844PubMedCrossRefGoogle Scholar
  101. 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 42:650–658PubMedCrossRefGoogle Scholar
  102. 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 183:4127–4134PubMedCrossRefGoogle Scholar
  103. 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 467:204–210PubMedCrossRefGoogle Scholar
  104. 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 65:197–208PubMedCrossRefGoogle Scholar
  105. 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 103:9023–9028PubMedPubMedCentralCrossRefGoogle Scholar
  106. 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 133:1792–1802PubMedCrossRefGoogle Scholar
  107. 107.
    Mouw JK, Ou G, Weaver VM (2014) Extracellular matrix assembly: a multiscale deconstruction. Nat Rev Mol Cell Biol 15:771–785PubMedPubMedCentralCrossRefGoogle Scholar
  108. 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 CrossRefGoogle Scholar
  109. 109.
    Koirala S, Jin Z, Piao X, Corfas G (2009) GPR56-regulated granule cell adhesion is essential for rostral cerebellar development. J Neurosci 29:7439–7449PubMedPubMedCentralCrossRefGoogle Scholar
  110. 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 102:2916–2924PubMedCrossRefGoogle Scholar
  111. 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 PubMedPubMedCentralCrossRefGoogle Scholar
  112. 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 85:755–769PubMedPubMedCentralCrossRefGoogle Scholar
  113. 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, HeidelbergGoogle Scholar
  114. 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 281:4878–4891PubMedCrossRefGoogle Scholar
  115. 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, HeidelbergGoogle Scholar
  116. 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 15:2145–2150PubMedCrossRefGoogle Scholar
  117. 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 13:385–392PubMedCrossRefGoogle Scholar
  118. 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 18:355–361PubMedGoogle Scholar
  119. 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 18:785–791PubMedGoogle Scholar
  120. 120.
    de Fraipont F, Nicholson AC, Feige JJ, Van Meir EG (2001) Thrombospondins and tumor angiogenesis. Trends Mol Med 7:401–407PubMedCrossRefGoogle Scholar
  121. 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 5:11PubMedPubMedCentralCrossRefGoogle Scholar
  122. 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 463:191–196PubMedCrossRefGoogle Scholar
  123. 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 31:1364–1378PubMedPubMedCentralCrossRefGoogle Scholar
  124. 124.
    Zhu D, Van Meir EG (2016) BAI1: from cancer to neurological disease. OncotargetGoogle Scholar
  125. 125.
    St Croix B, Rago C, Velculescu V, Traverso G, Romans KE, Montgomery E et al (2000) Genes expressed in human tumor endothelium. Science 289:1197–1202PubMedCrossRefGoogle Scholar
  126. 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 61:6649–6655PubMedGoogle Scholar
  127. 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 446:179–186PubMedCrossRefGoogle Scholar
  128. 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 79:103–108PubMedCrossRefGoogle Scholar
  129. 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 294:172–184PubMedCrossRefGoogle Scholar
  130. 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 176:2039–2050PubMedPubMedCentralCrossRefGoogle Scholar
  131. 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 247:597–604PubMedCrossRefGoogle Scholar
  132. 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 288:22248–22256PubMedPubMedCentralCrossRefGoogle Scholar
  133. 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 84:75–82PubMedCrossRefGoogle Scholar
  134. 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 14:6662–6672PubMedPubMedCentralCrossRefGoogle Scholar
  135. 135.
    Wang Q (2015) Identification of biomarkers for metastatic osteosarcoma based on DNA microarray data. Neoplasma 62:365–371PubMedCrossRefGoogle Scholar
  136. 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 443:32–37PubMedCrossRefGoogle Scholar
  137. 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 26:847–858PubMedCrossRefGoogle Scholar
  138. 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, e39989PubMedPubMedCentralCrossRefGoogle Scholar
  139. 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 52:83–88PubMedCrossRefGoogle Scholar
  140. 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 19:688–699PubMedCrossRefGoogle Scholar
  141. 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 9:334–338PubMedPubMedCentralCrossRefGoogle Scholar
  142. 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 184:1185–1189PubMedCrossRefGoogle Scholar
  143. 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 188:1442–1450PubMedCrossRefGoogle Scholar
  144. 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, e69451PubMedPubMedCentralCrossRefGoogle Scholar
  145. 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 3:1457–64PubMedPubMedCentralCrossRefGoogle Scholar
  146. 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 49:348–57PubMedPubMedCentralCrossRefGoogle Scholar
  147. 147.
    Yang L, Xu L (2012) GPR56 in cancer progression: current status and future perspective. Future Oncol 8:431–440PubMedCrossRefGoogle Scholar
  148. 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 80:738–743PubMedCrossRefGoogle Scholar
  149. 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 86:490–496PubMedPubMedCentralCrossRefGoogle Scholar
  150. 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 27:2579–2588PubMedCrossRefGoogle Scholar
  151. 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 22:261–272PubMedCrossRefGoogle Scholar
  152. 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 1491:75–92PubMedCrossRefGoogle Scholar
  153. 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, e91466PubMedPubMedCentralCrossRefGoogle Scholar
  154. 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 121:609–616PubMedCrossRefGoogle Scholar
  155. 155.
    Mosmann TR, Li L, Sad S (1997) Functions of CD8 T-cell subsets secreting different cytokine patterns. Semin Immunol 9:87–92PubMedCrossRefGoogle Scholar
  156. 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 11:863–869PubMedGoogle Scholar
  157. 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 12:617–624PubMedCrossRefGoogle Scholar
  158. 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 4:381–389PubMedCrossRefGoogle Scholar
  159. 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 25:499–507PubMedCrossRefGoogle Scholar

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

Personalised recommendations