Receptor tyrosine kinases: Principles and functions in glioma invasion

Advances in Experimental Medicine and Biology

Volumn 986, Issue , 2013, Pages 143-170

  Nakada, Mitsutoshi ^a   Kita, Daisuke ^a   Teng, Lei ^a,b   Pyko, Ilya V ^a   Watanabe, Takuya ^a   Hayashi, Yutaka ^a   Hamada, Jun Ichiro ^a  

^a KANAZAWA UNIVERSITY   (Japan)

^b HARBIN MEDICAL UNIVERSITY   (China)

Author keywords

Axl; c Met; Clinical trial; Cross talk; DDR1; EGFR; Eph; Glioblastoma; Glioma; Invasion; PDGFR; Tie; TrkA; Tyrosine kinase inhibitor; Tyrosine kinase receptor

Indexed keywords

ANGIOPOIETIN; AXL PROTEIN; CABOZANTINIB; CETUXIMAB; COLLAGEN; DASATINIB; DISCOIDIN DOMAIN RECEPTOR 1; EPHRIN; EPHRIN RECEPTOR; EPIDERMAL GROWTH FACTOR; EPIDERMAL GROWTH FACTOR RECEPTOR; EPIDERMAL GROWTH FACTOR RECEPTOR 2; ERLOTINIB; GEFITINIB; GROWTH ARREST SPECIFIC PROTEIN 6; IMATINIB; LAPATINIB; MONOCLONAL ANTIBODY I 125; NIMOTUZUMAB; PLATELET DERIVED GROWTH FACTOR; PLATELET DERIVED GROWTH FACTOR RECEPTOR; PROTEIN KINASE; PROTEIN TYROSINE KINASE; PROTEIN TYROSINE KINASE A; RECEPTOR PROTEIN; SCATTER FACTOR; SCATTER FACTOR RECEPTOR; SUNITINIB; TIE RECEPTOR; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ARTICLE; CANCER INVASION; DISEASE ASSOCIATION; DRUG EFFICACY; DRUG MECHANISM; DRUG RESPONSE; DRUG TARGETING; ENZYME ACTIVITY; GLIOBLASTOMA; GLIOMA; HUMAN; MOLECULAR PATHOLOGY; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN PROTEIN INTERACTION; SIGNAL TRANSDUCTION; TREATMENT OUTCOME; UNSPECIFIED SIDE EFFECT;

EID: 84867505122     PISSN: 00652598     EISSN: None     Source Type: Book Series    
DOI: 10.1007/978-94-007-4719-7_8     Document Type: Article

References (180)

1. Abounader R, Laterra J (2005) Scatter factor/hepatocyte growth factor in brain tumor growth and angiogenesis. Neuro Oncol 7:436-4511
2. Alves F, Vogel W, Mossie K, Millauer B, Ho fl er H, Ullrich A (1995) Distinct structural characteristics of discoidin I subfamily receptor tyrosine kinases and complementary expression in human cancer. Oncogene 10:609-6188
3. Andersson U, Guo D, Malmer B, Bergenheim AT, Brannstrom T, Hedman H, Henriksson R (2004) Epidermal growth factor receptor family (EGFR, ErbB2-4) in gliomas and meningiomas. Acta Neuropathol 108:135-1422
4. Barker FG 2nd, Simmons ML, Chang SM, Prados MD, Larson DA, Sneed PK, Wara WM, Berger MS, Chen P, Israel MA, Aldape KD (2001) EGFR overexpression and radiation response in glioblastoma multiforme. Int J Radiat Oncol Biol Phys 51:410-4188
5. Batchelor TT, Sorensen AG, Di Tomaso E, Zhang WT, Duda DG, Cohen KS, Kozak KR, Cahill DP, Chen PJ, Zhu M, Ancukiewicz M, Mrugala MM, Plotkin S, Drappatz J, Louis DN, Ivy P, Scadden DT, Benner T, Loef fl er JS, Wen PY, Jain RK (2007) AZD2171, a pan-VEGF receptor tyrosine kinase inhibitor, normalizes tumor vasculature and alleviates edema in glioblastoma patients. Cancer Cell 11:83-955
6. Batchelor T, Mulholland J, Neyns B et al (2010a) A phase III randomized study comparing the efficacy of cediranib as monotherapy, and in combination with lomustine, with lomustine alone in recurrent glioblastoma patients. Ann Oncol 21:44
7. Batchelor TT, Duda DG, Di Tomaso E, Ancukiewicz M, Plotkin SR, Gerstner E, Eichler AF, Drappatz J, Hochberg FH, Benner T, Louis DN, Cohen KS, Chea H, Exarhopoulos A, Loef fl er JS, Moses MA, Ivy P, Sorensen AG, Wen PY, Jain RK (2010b) Phase II study of cediranib, an oral pan-vascular endothelial growth factor receptor tyrosine kinase inhibitor, in patients with recurrent glioblastoma. J Clin Oncol 28:2817-28233
8. Belda-Iniesta C, Carpeno Jde C, Saenz EC, Gutierrez M, Perona R, Baron MG (2006) Long term responses with cetuximab therapy in glioblastoma multiforme. Cancer Biol Ther 5:912-9144
9. Ben-Levy R, Paterson HF, Marshall CJ, Yarden Y (1994) A single autophosphorylation site confers oncogenicity to the Neu/ErbB-2 receptor and enables coupling to the MAP kinase pathway. EMBO J 13:3302-33111
10. Blume-Jensen P, Hunter T (2001) Oncogenic kinase signalling. Nature 411:355-3655
11. Bogdan S, Klambt C (2001) Epidermal growth factor receptor signaling. Curr Biol 11:R292-2955
12. Brinckerhoff CE, Matrisian LM (2002) Matrix metalloproteinases: a tail of a frog that became a prince. Nat Rev Mol Cell Biol 3:207-2144
13. Broniscer A, Baker JN, Tagen M, Onar-Thomas A, Gilbertson RJ, Davidoff AM, Pai Panandiker AS, Leung W, Chin TK, Stewart CF, Kocak M, Rowland C, Merchant TE, Kaste SC, Gajjar A (2010) Phase I study of vandetanib during and after radiotherapy in children with diffuse intrinsic pontine glioma. J Clin Oncol 28:4762-47688
14. Brunckhorst MK, Wang H, Lu R, Yu Q (2010) Angiopoietin-4 promotes glioblastoma progression by enhancing tumor cell viability and angiogenesis. Cancer Res 70:7283-72933
15. Burgess T, Coxon A, Meyer S, Sun J, Rex K, Tsuruda T, Chen Q, Ho SY, Li L, Kaufman S, Mcdorman K, Cattley RC, Elliott G, Zhang K, Feng X, Jia XC, Green L, Radinsky R, Kendall R (2006) Fully human monoclonal antibodies to hepatocyte growth factor with therapeutic potential against hepatocyte growth factor/c-Met-dependent human tumors. Cancer Res 66:1721-17299
16. Cai XM, Tao BB, Wang LY, Liang YL, Jin JW, Yang Y, Hu YL, Zha XL (2005) Protein phosphatase activity of PTEN inhibited the invasion of glioma cells with epidermal growth factor receptor mutation type III expression. Int J Cancer 117:905-9122
17. Campbell TN, Robbins SM (2008) The Eph receptor/ephrin system: an emerging player in the invasion game. Curr Issues Mol Biol 10:61-666
18. Cancer Genome Atlas Research Network (2008) Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature 455:1061-10688
19. Cattaneo MG, Gentilini D, Vicentini LM (2006) Deregulated human glioma cell motility: inhibitory effect of somatostatin. Mol Cell Endocrinol 256:34-399
20. Cecchi F, Rabe DC, Bottaro DP (2010) Targeting the HGF/Met signalling pathway in cancer. Eur J Cancer 46:1260-12700
21. Chow LQ, Eckhardt SG (2007) Sunitinib: from rational design to clinical efficacy. J Clin Oncol 25:884-8966
22. Chuang YY, Tran NL, Rusk N, Nakada M, Berens ME, Symons M (2004) Role of synaptojanin 2 in glioma cell migration and invasion. Cancer Res 64:8271-82755
23. Citri A, Skaria KB, Yarden Y (2003) The deaf and the dumb: the biology of ErbB-2 and ErbB-3. Exp Cell Res 284:54-655
24. Cooper CS, Park M, Blair DG, Tainsky MA, Huebner K, Croce CM, Vande Woude GF (1984) Molecular cloning of a new transforming gene from a chemically transformed human cell line. Nature 311:29-333
25. Demetri GD, Von Mehren M, Blanke CD, Van Den Abbeele AD, Eisenberg B, Roberts PJ, Heinrich MC, Tuveson DA, Singer S, Janicek M, Fletcher JA, Silverman SG, Silberman SL, Capdeville R, Kiese B, Peng B, Dimitrijevic S, Druker BJ, Corless C, Fletcher CD, Joensuu H (2002) Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med 347:472-4800
26. Dresemann G, Weller M, Rosenthal MA, Wedding U, Wagner W, Engel E, Heinrich B, Mayer-Steinacker R, Karup-Hansen A, Fluge O, Nowak A, Mehdorn M, Schleyer E, Krex D, Olver IN, Steinbach JP, Hosius C, Sieder C, Sorenson G, Parker R, Nikolova Z (2010) Imatinib in combination with hydroxyurea versus hydroxyurea alone as oral therapy in patients with progressive pretreated glioblastoma resistant to standard dose temozolomide. J Neurooncol 96:393-4022
27. Druker BJ, Talpaz M, Resta DJ, Peng B, Buchdunger E, Ford JM, Lydon NB, Kantarjian H, Capdeville R, Ohno-Jones S, Sawyers CL (2001) Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N Engl J Med 344:1031-10377
28. Du J, Bernasconi P, Clauser KR, Mani DR, Finn SP, Beroukhim R, Burns M, Julian B, Peng XP, Hieronymus H, Maglathlin RL, Lewis TA, Liau LM, Nghiemphu P, Mellinghoff IK, Louis DN, Loda M, Carr SA, Kung AL, Golub TR (2009) Bead-based pro filing of tyrosine kinase phosphorylation identi fies SRC as a potential target for glioblastoma therapy. Nat Biotechnol 27:77-833
29. Edwards LA, Woolard K, Son MJ, Li A, Lee J, Ene C, Mantey SA, Maric D, Song H, Belova G, Jensen RT, Zhang W, Fine HA (2011) Effect of brain-and tumor-derived connective tissue growth factor on glioma invasion. J Natl Cancer Inst 103:1162-11788
30. Ekstrand AJ, Sugawa N, James CD, Collins VP (1992) Ampli fied and rearranged epidermal growth factor receptor genes in human glioblastomas reveal deletions of sequences encoding portions of the N-and/or C-terminal tails. Proc Natl Acad Sci U S A 89:4309-43133
31. Eller JL, Longo SL, Kyle MM, Bassano D, Hicklin DJ, Canute GW (2005) Anti-epidermal growth factor receptor monoclonal antibody cetuximab augments radiation effects in glioblastoma multiforme in vitro and in vivo. Neurosurgery 56:155-162, discussion 1622
32. Emrich JG, Brady LW, Quang TS, Class R, Miyamoto C, Black P, Rodeck U (2002) Radioiodinated (I-125) monoclonal antibody 425 in the treatment of high grade glioma patients: ten-year synopsis of a novel treatment. Am J Clin Oncol 25:541-5466
33. Engelhard HH, Wolters M, Criswell PS (1995) Analysis of c-erbB2 protein content of human glioma cells and tumor tissue. J Neurooncol 23:31-400
34. Erber R, Eichelsbacher U, Powajbo V, Korn T, Djonov V, Lin J, Hammes HP, Grobholz R, Ullrich A, Vajkoczy P (2006) EphB4 controls blood vascular morphogenesis during postnatal angiogenesis. EMBO J 25:628-6411
35. Escalante M, Courtney J, Chin WG, Teng KK, Kim JI, Fajardo JE, Mayer BJ, Hempstead BL, Birge RB (2000) Phosphorylation of c-Crk II on the negative regulatory Tyr222 mediates nerve growth factor-induced cell spreading and morphogenesis. J Biol Chem 275:24787-247977
36. Feldkamp MM, Lala P, Lau N, Roncari L, Guha A (1999) Expression of activated epidermal growth factor receptors, Ras-guanosine triphosphate, and mitogen-activated protein kinase in human glioblastoma multiforme specimens. Neurosurgery 45:1442-14533
37. Fleming TP, Saxena A, Clark WC, Robertson JT, Old fi eld EH, Aaronson SA, Ali IU (1992) Ampli fication and/or overexpression of platelet-derived growth factor receptors and epidermal growth factor receptor in human glial tumors. Cancer Res 52:4550-45533
38. Franceschi E, Cavallo G, Lonardi S, Magrini E, Tosoni A, Grosso D, Scopece L, Blatt V, Urbini B, Pession A, Tallini G, Crino L, Brandes AA (2007) Ge fitinib in patients with progressive high-grade gliomas: a multicentre phase II study by Gruppo Italiano Cooperativo di Neuro-Oncologia (GICNO). Br J Cancer 96:1047-10511
39. Friedman HS, Prados MD, Wen PY, Mikkelsen T, Schiff D, Abrey LE, Yung WK, Paleologos N, Nicholas MK, Jensen R, Vredenburgh J, Huang J, Zheng M, Cloughesy T (2009) Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. J Clin Oncol 27:4733-47400
40. Fukai J, Yokote H, Yamanaka R, Arao T, Nishio K, Itakura T (2008) EphA4 promotes cell proliferation and migration through a novel EphA4-FGFR1 signaling pathway in the human glioma U251 cell line. Mol Cancer Ther 7:2768-27788
41. Gale NW, Holland SJ, Valenzuela DM, Flenniken A, Pan L, Ryan TE, Henkemeyer M, Strebhardt K, Hirai H, Wilkinson DG, Pawson T, Davis S, Yancopoulos GD (1996) Eph receptors and ligands comprise two major specificity subclasses and are reciprocally compartmentalized during embryogenesis. Neuron 17:9-199
42. Gale NW, Thurston G, Hackett SF, Renard R, Wang Q, Mcclain J, Martin C, Witte C, Witte MH, Jackson D, Suri C, Campochiaro PA, Wiegand SJ, Yancopoulos GD (2002) Angiopoietin-2 is required for postnatal angiogenesis and lymphatic patterning, and only the latter role is rescued by Angiopoietin-1. Dev Cell 3:411-4233
43. Gao L, Li F, Dong B, Zhang J, Rao Y, Cong Y, Mao B, Chen X (2010) Inhibition of STAT3 and ErbB2 suppresses tumor growth, enhances radiosensitivity, and induces mitochondria-dependent apoptosis in glioma cells. Int J Radiat Oncol Biol Phys 77:1223-12311
44. Gilbertson RJ, Perry RH, Kelly PJ, Pearson AD, Lunec J (1997) Prognostic signi ficance of HER2 and HER4 coexpression in childhood medulloblastoma. Cancer Res 57:3272-32800
45. Gilbertson RJ, Bentley L, Hernan R, Junttila TT, Frank AJ, Haapasalo H, Connelly M, Wetmore C, Curran T, Elenius K, Ellison DW (2002) ERBB receptor signaling promotes ependymoma cell proliferation and represents a potential novel therapeutic target for this disease. Clin Cancer Res 8:3054-30644
46. Gondi CS, Dinh DH, Klopfenstein JD, Gujrati M, Rao JS (2009) MMP-2 downregulation mediates differential regulation of cell death via ErbB-2 in glioma xenografts. Int J Oncol 35:257-2633
47. Gu J, Tamura M, Pankov R, Danen EH, Takino T, Matsumoto K, Yamada KM (1999) Shc and FAK differentially regulate cell motility and directionality modulated by PTEN. J Cell Biol 146:389-4033
48. Guha A, Dashner K, Black PM, Wagner JA, Stiles CD (1995) Expression of PDGF and PDGF receptors in human astrocytoma operation specimens supports the existence of an autocrine loop. Int J Cancer 60:168-1733
49. Gulati S, Ytterhus B, Granli US, Gulati M, Lydersen S, Torp SH (2010) Overexpression of c-erbB2 is a negative prognostic factor in anaplastic astrocytomas. Diagn Pathol 5:188
50. Haapasalo H, Hyytinen E, Sallinen P, Helin H, Kallioniemi OP, Isola J (1996) c-erbB-2 in astrocytomas: infrequent overexpression by immunohistochemistry and absence of gene amplification by fluorescence in situ hybridization. Br J Cancer 73:620-6233
51. Haas-Kogan DA, Prados MD, Tihan T, Eberhard DA, Jelluma N, Arvold ND, Baumber R, Lamborn KR, Kapadia A, Malec M, Berger MS, Stokoe D (2005) Epidermal growth factor receptor, protein kinase B/Akt, and glioma response to erlotinib. J Natl Cancer Inst 97:880-8877
52. Ha fi zi S, Dahlback B (2006) Signalling and functional diversity within the Axl subfamily of receptor tyrosine kinases. Cytokine Growth Factor Rev 17:295-3044
53. Hainsworth JD, Ervin T, Friedman E, Priego V, Murphy PB, Clark BL, Lamar RE (2010) Concurrent radiotherapy and temozolomide followed by temozolomide and sorafenib in the first-line treatment of patients with glioblastoma multiforme. Cancer 116:3663-36699
54. Hawighorst T, Skobe M, Streit M, Hong YK, Velasco P, Brown LF, Riccardi L, Lange-Asschenfeldt B, Detmar M (2002) Activation of the tie2 receptor by angiopoietin-1 enhances tumor vessel maturation and impairs squamous cell carcinoma growth. Am J Pathol 160:1381-13922
55. Hayes AJ, Huang WQ, Yu J, Maisonpierre PC, Liu A, Kern FG, Lippman ME, Mcleskey SW, Li LY (2000) Expression and function of angiopoietin-1 in breast cancer. Br J Cancer 83:1154-11600
56. Hegi ME, Diserens AC, Bady P, Kamoshima Y, Kouwenhoven MC, Delorenzi M, Lambiv WL, Hamou MF, Matter MS, Koch A, Heppner FL, Yonekawa Y, Merlo A, Frei K, Mariani L, Hofer S (2011) Pathway analysis of glioblastoma tissue after preoperative treatment with the EGFR tyrosine kinase inhibitor gefitinib-a phase II trial. Mol Cancer Ther 10:1102-11122
57. Hermanson M, Funa K, Hartman M, Claesson-Welsh L, Heldin CH, Westermark B, Nister M (1992) Platelet-derived growth factor and its receptors in human glioma tissue: expression of messenger RNA and protein suggests the presence of autocrine and paracrine loops. Cancer Res 52:3213-32199
58. Heroult M, Schaffner F, Augustin HG (2006) Eph receptor and ephrin ligand-mediated interactions during angiogenesis and tumor progression. Exp Cell Res 312:642-6500
59. Hiesiger EM, Hayes RL, Pierz DM, Budzilovich GN (1993) Prognostic relevance of epidermal growth factor receptor (EGF-R) and c-neu/erbB2 expression in glioblastomas (GBMs). J Neurooncol 16:93-1044
60. Hoelzinger DB, Demuth T, Berens ME (2007) Autocrine factors that sustain glioma invasion and paracrine biology in the brain microenvironment. J Natl Cancer Inst 99:1583-15933
61. Hortobagyi GN (2005) Trastuzumab in the treatment of breast cancer. N Engl J Med 353:1734-17366
62. Hu B, Jarzynka MJ, Guo P, Imanishi Y, Schlaepfer DD, Cheng SY (2006) Angiopoietin 2 induces glioma cell invasion by stimulating matrix metalloprotease 2 expression through the alphavbeta1 integrin and focal adhesion kinase signaling pathway. Cancer Res 66:775-7833
63. Huang PH, Cavenee WK, Furnari FB, White FM (2007) Uncovering therapeutic targets for glioblastoma: a systems biology approach. Cell Cycle 6:2750-27544
64. Hutterer M, Knyazev P, Abate A, Reschke M, Maier H, Stefanova N, Knyazeva T, Barbieri V, Reindl M, Muigg A, Kostron H, Stockhammer G, Ullrich A (2008) Axl and growth arrest-specific gene 6 are frequently overexpressed in human gliomas and predict poor prognosis in patients with glioblastoma multiforme. Clin Cancer Res 14:130-1388
65. Janssen JW, Schulz AS, Steenvoorden AC, Schmidberger M, Strehl S, Ambros PF, Bartram CR (1991) A novel putative tyrosine kinase receptor with oncogenic potential. Oncogene 6:2113-21200
66. Jones RB, Gordus A, Krall JA, Macbeath G (2006) A quantitative protein interaction network for the ErbB receptors using protein microarrays. Nature 439:168-1744
67. Jorissen RN, Walker F, Pouliot N, Garrett TP, Ward CW, Burgess AW (2003) Epidermal growth factor receptor: mechanisms of activation and signalling. Exp Cell Res 284:31-533
68. Khoshyomn S, Penar PL, Rossi J, Wells A, Abramson DL, Bhushan A (1999) Inhibition of phospholipase C-gamma1 activation blocks glioma cell motility and invasion of fetal rat brain aggregates. Neurosurgery 44:568-577, discussion 577-5688
69. Kita D, Takino T, Nakada M, Takahashi T, Yamashita J, Sato H (2001) Expression of dominant-negative form of Ets-1 suppresses fi bronectin-stimulated cell adhesion and migration through down-regulation of integrin alpha5 expression in U251 glioma cell line. Cancer Res 61:7985-79911
70. Kita D, Yonekawa Y, Weller M, Ohgaki H (2007) PIK3CA alterations in primary (de novo) and secondary glioblastomas. Acta Neuropathol 113:295-3022
71. Koga K, Todaka T, Morioka M, Hamada J, Kai Y, Yano S, Okamura A, Takakura N, Suda T, Ushio Y (2001) Expression of angiopoietin-2 in human glioma cells and its role for angiogenesis. Cancer Res 61:6248-62544
72. Koochekpour S, Jeffers M, Rulong S, Taylor G, Klineberg E, Hudson EA, Resau JH, Vande Woude GF (1997) Met and hepatocyte growth factor/scatter factor expression in human gliomas. Cancer Res 57:5391-53988
73. Kullander K, Klein R (2002) Mechanisms and functions of Eph and ephrin signalling. Nat Rev Mol Cell Biol 3:475-4866
74. Lam C, Bouffet E, Bartels U (2009) Nimotuzumab in pediatric glioma. Future Oncol 5:1349-13611
75. Lamszus K, Laterra J, Westphal M, Rosen EM (1999) Scatter factor/hepatocyte growth factor (SF/HGF) content and function in human gliomas. Int J Dev Neurosci 17:517-5300
76. Lassman AB, Rossi MR, Raizer JJ, Abrey LE, Lieberman FS, Grefe CN, Lamborn K, Pao W, Shih AH, Kuhn JG, Wilson R, Nowak NJ, Cowell JK, Deangelis LM, Wen P, Gilbert MR, Chang S, Yung WA, Prados M, Holland EC (2005) Molecular study of malignant gliomas treated with epidermal growth factor receptor inhibitors: tissue analysis from North American Brain Tumor Consortium Trials 01-03 and 00-01. Clin Cancer Res 11:7841-78500
77. Lee HS, Han J, Bai HJ, Kim KW (2009) Brain angiogenesis in developmental and pathological processes: regulation, molecular and cellular communication at the neurovascular interface. FEBS J 276:4622-46355
78. Li L, Quang TS, Gracely EJ, Kim JH, Emrich JG, Yaeger TE, Jenrette JM, Cohen SC, Black P, Brady LW (2010) A phase II study of anti-epidermal growth factor receptor radioimmunotherapy in the treatment of glioblastoma multiforme. J Neurosurg 113:192-1988
79. Liang ML, Ma J, Ho M, Solomon L, Bouffet E, Rutka JT, Hawkins C (2008) Tyrosine kinase expression in pediatric high grade astrocytoma. J Neurooncol 87:247-2533
80. Libermann TA, Nusbaum HR, Razon N, Kris R, Lax I, Soreq H, Whittle N, Water fi eld MD, Ullrich A, Schlessinger J (1985) Ampli fication and overexpression of the EGF receptor gene in primary human glioblastomas. J Cell Sci Suppl 3:161-1722
81. Liu D, Martin V, Fueyo J, Lee OH, Xu J, Cortes-Santiago N, Alonso MM, Aldape K, Colman H, Gomez-Manzano C (2010) Tie2/TEK modulates the interaction of glioma and brain tumor stem cells with endothelial cells and promotes an invasive phenotype. Oncotarget 1:700-7099
82. Lohi J (2001) Laminin-5 in the progression of carcinomas. Int J Cancer Journal international du cancer 94:763-7677
83. Lokker NA, Sullivan CM, Hollenbach SJ, Israel MA, Giese NA (2002) Platelet-derived growth factor (PDGF) autocrine signaling regulates survival and mitogenic pathways in glioblastoma cells: evidence that the novel PDGF-C and PDGF-D ligands may play a role in the development of brain tumors. Cancer Res 62:3729-37355
84. Machein MR, Knedla A, Knoth R, Wagner S, Neuschl E, Plate KH (2004) Angiopoietin-1 promotes tumor angiogenesis in a rat glioma model. Am J Pathol 165:1557-15700
85. Maisonpierre PC, Suri C, Jones PF, Bartunkova S, Wiegand SJ, Radziejewski C, Compton D, Mcclain J, Aldrich TH, Papadopoulos N, Daly TJ, Davis S, Sato TN, Yancopoulos GD (1997) Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis. Science 277:55-600
86. Majumdar K, Radotra BD, Vasishta RK, Pathak A (2009) Platelet-derived growth factor expression correlates with tumor grade and proliferative activity in human oligodendrogliomas. Surg Neurol 72:54-600
87. Man fi oletti G, Brancolini C, Avanzi G, Schneider C (1993) The protein encoded by a growth arrest-specific gene (gas6) is a new member of the vitamin K-dependent proteins related to protein S, a negative coregulator in the blood coagulation cascade. Mol Cell Biol 13:4976-49855
88. Manning G, Whyte DB, Martinez R, Hunter T, Sudarsanam S (2002) The protein kinase complement of the human genome. Science 298:1912-19344
89. Martinho O, Longatto-Filho A, Lambros MB, Martins A, Pinheiro C, Silva A, Pardal F, Amorim J, Mackay A, Milanezi F, Tamber N, Fenwick K, Ashworth A, Reis-Filho JS, Lopes JM, Reis RM (2009) Expression, mutation and copy number analysis of platelet-derived growth factor receptor A (PDGFRA) and its ligand PDGFA in gliomas. Br J Cancer 101:973-9822
90. Mateos ME, Lopez-Laso E, Izquierdo L, Perez-Navero JL, Garcia S, Garzas C (2011) Response to nimotuzumab in a child with a progressive diffuse intrinsic pontine glioma. Pediatr Int 53:261-2633
91. Meakin SO, Macdonald JI, Gryz EA, Kubu CJ, Verdi JM (1999) The signaling adapter FRS-2 competes with Shc for binding to the nerve growth factor receptor TrkA. A model for discriminating proliferation and differentiation. J Biol Chem 274:9861-98700
92. Mellinghoff IK, Wang MY, Vivanco I, Haas-Kogan DA, Zhu S, Dia EQ, Lu KV, Yoshimoto K, Huang JH, Chute DJ, Riggs BL, Horvath S, Liau LM, Cavenee WK, Rao PN, Beroukhim R, Peck TC, Lee JC, Sellers WR, Stokoe D, Prados M, Cloughesy TF, Sawyers CL, Mischel PS (2005) Molecular determinants of the response of glioblastomas to EGFR kinase inhibitors. N Engl J Med 353:2012-20244
93. Miao H, Li DQ, Mukherjee A, Guo H, Petty A, Cutter J, Basilion JP, Sedor J, Wu J, Danielpour D, Sloan AE, Cohen ML, Wang B (2009) EphA2 mediates ligand-dependent inhibition and ligand-independent promotion of cell migration and invasion via a reciprocal regulatory loop with Akt. Cancer Cell 16:9-200
94. Mineo JF, Bordron A, Baroncini M, Maurage CA, Ramirez C, Siminski RM, Berthou C, Dam Hieu P (2007) Low HER2-expressing glioblastomas are more often secondary to anaplastic transformation of low-grade glioma. J Neurooncol 85:281-2877
95. Miyamori H, Hasegawa K, Kim KR, Sato H (2000) Expression of metastasis-associated mts1 gene is co-induced with membrane type-1 matrix metalloproteinase (MT1-MMP) during oncogenic transformation and tubular formation of Madin Darby canine kidney (MDCK) epithelial cells. Clin Exp Metastasis 18:51-566
96. Moriyama T, Kataoka H, Tsubouchi H, Koono M (1995) Concomitant expression of hepatocyte growth factor (HGF), HGF activator and c-met genes in human glioma cells in vitro. FEBS Lett 372:78-822
97. Moriyama T, Kataoka H, Hamasuna R, Yokogami K, Uehara H, Kawano H, Goya T, Tsubouchi H, Koono M, Wakisaka S (1998a) Up-regulation of vascular endothelial growth factor induced by hepatocyte growth factor/scatter factor stimulation in human glioma cells. Biochem Biophys Res Commun 249:73-777
98. Moriyama T, Kataoka H, Kawano H, Yokogami K, Nakano S, Goya T, Uchino H, Koono M, Wakisaka S (1998b) Comparative analysis of expression of hepatocyte growth factor and its receptor, c-met, in gliomas, meningiomas and schwannomas in humans. Cancer Lett 124:149-1555
99. Nagane M (2011) Neuro-oncology: continuing multidisciplinary progress. Lancet Neurol 10:18-200
100. Nakada M, Kita D, Futami K, Yamashita J, Fujimoto N, Sato H, Okada Y (2001) Roles of membrane type 1 matrix metalloproteinase and tissue inhibitor of metalloproteinases 2 in invasion and dissemination of human malignant glioma. J Neurosurg 94:464-4733
101. Nakada M, Niska JA, Miyamori H, Mcdonough WS, Wu J, Sato H, Berens ME (2004) The phosphorylation of EphB2 receptor regulates migration and invasion of human glioma cells. Cancer Res 64:3179-31855
102. Nakada M, Niska JA, Tran NL, Mcdonough WS, Berens ME (2005) EphB2/R-Ras signaling regulates glioma cell adhesion, growth, and invasion. Am J Pathol 167:565-5766
103. Nakada M, Drake KL, Nakada S, Niska JA, Berens ME (2006) Ephrin-B3 ligand promotes glioma invasion through activation of Rac1. Cancer Res 66:8492-85000
104. Nakada M, Nakada S, Demuth T, Tran NL, Hoelzinger DB, Berens ME (2007) Molecular targets of glioma invasion. Cell Mol Life Sci 64:458-4788
105. Nakada M, Anderson EM, Demuth T, Nakada S, Reavie LB, Drake KL, Hoelzinger DB, Berens ME (2010) The phosphorylation of ephrin-B2 ligand promotes glioma cell migration and invasion. Int J Cancer 126:1155-11655
106. Nakada M, Hayashi Y, Hamada J (2011) Role of Eph/ephrin tyrosine kinase in malignant glioma. Neuro Oncol 13:1163-11700
107. Natarajan M, Stewart JE, Golemis EA, Pugacheva EN, Alexandropoulos K, Cox BD, Wang W, Grammer JR, Gladson CL (2006) HEF1 is a necessary and specific downstream effector of FAK that promotes the migration of glioblastoma cells. Oncogene 25:1721-17322
108. Neyns B, Sadones J, Joosens E, Bouttens F, Verbeke L, Baurain JF, D'hondt L, Strauven T, Chaskis C, In't Veld P, Michotte A, De Greve J (2009) Strati fied phase II trial of cetuximab in patients with recurrent high-grade glioma. Ann Oncol 20:1596-16033
109. Neyns B, Sadones J, Chaskis C, Dujardin M, Everaert H, Lv S, Duerinck J, Tynninen O, Nupponen N, Michotte A, De Greve J (2011) Phase II study of sunitinib malate in patients with recurrent high-grade glioma. J Neurooncol 103:491-5011
110. Nister M, Libermann TA, Betsholtz C, Pettersson M, Claesson-Welsh L, Heldin CH, Schlessinger J, Westermark B (1988) Expression of messenger RNAs for platelet-derived growth factor and transforming growth factor-alpha and their receptors in human malignant glioma cell lines. Cancer Res 48:3910-39188
111. Normanno N, De Luca A, Bianco C, Strizzi L, Mancino M, Maiello MR, Carotenuto A, De Feo G, Caponigro F, Salomon DS (2006) Epidermal growth factor receptor (EGFR) signaling in cancer. Gene 366:2-166
112. Ohgaki H, Kleihues P (2009) Genetic alterations and signaling pathways in the evolution of gliomas. Cancer Sci 100:2235-22411
113. Ohgaki H, Dessen P, Jourde B, Horstmann S, Nishikawa T, Di Patre PL, Burkhard C, Schuler D, Probst-Hensch NM, Maiorka PC, Baeza N, Pisani P, Yonekawa Y, Yasargil MG, Lutolf UM, Kleihues P (2004) Genetic pathways to glioblastoma: a population-based study. Cancer Res 64:6892-68999
114. Onishi M, Ichikawa T, Kurozumi K, Date I (2011) Angiogenesis and invasion in glioma. Brain Tumor Pathol 28:13-244
115. Ozawa T, Brennan CW, Wang L, Squatrito M, Sasayama T, Nakada M, Huse JT, Pedraza A, Utsuki S, Yasui Y, Tandon A, Fomchenko EI, Oka H, Levine RL, Fujii K, Ladanyi M, Holland EC (2010) PDGFRA gene rearrangements are frequent genetic events in PDGFRA-ampli fied glioblastomas. Genes Dev 24:2205-22188
116. Pedersen MW, Pedersen N, Ottesen LH, Poulsen HS (2005) Differential response to ge fitinib of cells expressing normal EGFR and the mutant EGFRvIII. Br J Cancer 93:915-9233
117. Peereboom DM, Shepard DR, Ahluwalia MS, Brewer CJ, Agarwal N, Stevens GH, Suh JH, Toms SA, Vogelbaum MA, Weil RJ, Elson P, Barnett GH (2010) Phase II trial of erlotinib with temozolomide and radiation in patients with newly diagnosed glioblastoma multiforme. J Neurooncol 98:93-999
118. Pflug BR, Colangelo AM, Tornatore C, Mocchetti I (2001) TrkA induces differentiation but not apoptosis in C6-2B glioma cells. J Neurosci Res 64:636-6455
119. Plate KH, Breier G, Farrell CL, Risau W (1992) Platelet-derived growth factor receptor-beta is induced during tumor development and upregulated during tumor progression in endothelial cells in human gliomas. Lab Invest 67:529-5344
120. Pollack IF, Stewart CF, Kocak M, Poussaint TY, Broniscer A, Banerjee A, Douglas JG, Kun LE, Boyett JM, Geyer JR (2011) A phase II study of ge fitinib and irradiation in children with newly diagnosed brainstem gliomas: a report from the Pediatric Brain Tumor Consortium. Neuro Oncol 13:290-2977
121. Ponzetto C, Bardelli A, Zhen Z, Maina F, Dalla Zonca P, Giordano S, Graziani A, Panayotou G, Comoglio PM (1994) A multifunctional docking site mediates signaling and transformation by the hepatocyte growth factor/scatter factor receptor family. Cell 77:261-2711
122. Prigent SA, Gullick WJ (1994) Identification of c-erbB-3 binding sites for phosphatidylinositol 3′-kinase and SHC using an EGF receptor/c-erbB-3 chimera. EMBO J 13:2831-28411
123. Quang TS, Brady LW (2004) Radioimmunotherapy as a novel treatment regimen: 125I-labeled monoclonal antibody 425 in the treatment of high-grade brain gliomas. Int J Radiat Oncol Biol Phys 58:972-9755
124. Rabin SJ, Tornatore C, Baker-Cairns B, Spiga G, Mocchetti I (1998) TrkA receptors delay C6-2B glioma cell growth in rat striatum. Brain Res Mol Brain Res 56:273-2766
125. Raizer JJ, Abrey LE, Lassman AB, Chang SM, Lamborn KR, Kuhn JG, Yung WK, Gilbert MR, Aldape KA, Wen PY, Fine HA, Mehta M, Deangelis LM, Lieberman F, Cloughesy TF, Robins HI, Dancey J, Prados MD (2010) A phase II trial of erlotinib in patients with recurrent malignant gliomas and nonprogressive glioblastoma multiforme postradiation therapy. Neuro Oncol 12:95-1033
126. Ram R, Lorente G, Nikolich K, Urfer R, Foehr E, Nagavarapu U (2006) Discoidin domain receptor-1a (DDR1a) promotes glioma cell invasion and adhesion in association with matrix metalloproteinase-2. J Neurooncol 76:239-2488
127. Ramnarain DB, Park S, Lee DY, Hatanpaa KJ, Scoggin SO, Otu H, Libermann TA, Raisanen JM, Ashfaq R, Wong ET, Wu J, Elliott R, Habib AA (2006) Differential gene expression analysis reveals generation of an autocrine loop by a mutant epidermal growth factor receptor in glioma cells. Cancer Res 66:867-8744
128. Raymond E, Brandes AA, Dittrich C, Fumoleau P, Coudert B, Clement PM, Frenay M, Rampling R, Stupp R, Kros JM, Heinrich MC, Gorlia T, Lacombe D, Van Den Bent MJ (2008) Phase II study of imatinib in patients with recurrent gliomas of various histologies: a European Organisation for Research and Treatment of Cancer Brain Tumor Group Study. J Clin Oncol 26:4659-46655
129. Reardon DA, Egorin MJ, Quinn JA, Rich JN, Gururangan S, Vredenburgh JJ, Desjardins A, Sathornsumetee S, Provenzale JM, Herndon JE 2nd, Dowell JM, Badruddoja MA, Mclendon RE, Lagattuta TF, Kicielinski KP, Dresemann G, Sampson JH, Friedman AH, Salvado AJ, Friedman HS (2005) Phase II study of imatinib mesylate plus hydroxyurea in adults with recurrent glioblastoma multiforme. J Clin Oncol 23:9359-93688
130. Reardon DA, Vredenburgh JJ, Desjardins A, Peters K, Gururangan S, Sampson JH, Marcello J, Herndon JE 2nd, Mclendon RE, Janney D, Friedman AH, Bigner DD, Friedman HS (2011) Effect of CYP3A-inducing anti-epileptics on sorafenib exposure: results of a phase II study of sorafenib plus daily temozolomide in adults with recurrent glioblastoma. J Neurooncol 101:57-666
131. Ribom D, Andrae J, Frielingsdorf M, Hartman M, Nister M, Smits A (2002) Prognostic value of platelet derived growth factor alpha receptor expression in grade 2 astrocytomas and oligoastrocytomas. J Neurol Neurosurg Psychiatry 72:782-7877
132. Rich JN, Rasheed BK, Yan H (2004) EGFR mutations and sensitivity to ge fitinib. N Engl J Med 351:1260-1261, author reply 1260-12611
133. Rosario M, Birchmeier W (2003) How to make tubes: signaling by the Met receptor tyrosine kinase. Trends Cell Biol 13:328-3355
134. Salhia B, Rutten F, Nakada M, Beaudry C, Berens M, Kwan A, Rutka JT (2005) Inhibition of Rho-kinase affects astrocytoma morphology, motility, and invasion through activation of Rac1. Cancer Res 65:8792-88000
135. Sato H, Takino T, Okada Y, Cao J, Shinagawa A, Yamamoto E, Seiki M (1994) A matrix metalloproteinase expressed on the surface of invasive tumour cells. Nature 370:61-655
136. Saurez G, Cabanas R, Zaldivar M, Garnier T, Iglesias B, Piedra P, Castillo MR, Longchong M, Iznaga N, Lage A (2009) Clinical experience with nimotuzumab in cuban pediatric patients with brain tumors, 2005 to 2007. MEDICC Rev 11:27-333
137. Schlessinger J (2000) Cell signaling by receptor tyrosine kinases. Cell 103:211-2255
138. Schwechheimer K, Lau fl e RM, Schmahl W, Knodlseder M, Fischer H, Ho fl er H (1994) Expression of neu/c-erbB-2 in human brain tumors. Hum Pathol 25:772-7800
139. Senner V, Ratzinger S, Mertsch S, Grassel S, Paulus W (2008) Collagen XVI expression is upregulated in glioblastomas and promotes tumor cell adhesion. FEBS Lett 582:3293-33000
140. Shih AH, Holland EC (2006) Platelet-derived growth factor (PDGF) and glial tumorigenesis. Cancer Lett 232:139-1477
141. Shinojima N, Tada K, Shiraishi S, Kamiryo T, Kochi M, Nakamura H, Makino K, Saya H, Hirano H, Kuratsu J, Oka K, Ishimaru Y, Ushio Y (2003) Prognostic value of epidermal growth factor receptor in patients with glioblastoma multiforme. Cancer Res 63:6962-69700
142. Singer HS, Hansen B, Martinie D, Karp CL (1999) Mitogenesis in glioblastoma multiforme cell lines: a role for NGF and its TrkA receptors. J Neurooncol 45:1-88
143. Spencer KS, Graus-Porta D, Leng J, Hynes NE, Klemke RL (2000) ErbB2 is necessary for induction of carcinoma cell invasion by ErbB family receptor tyrosine kinases. J Cell Biol 148:385-3977
144. Stephens P, Hunter C, Bignell G, Edkins S, Davies H, Teague J, Stevens C, O'meara S, Smith R, Parker A, Barthorpe A, Blow M, Brackenbury L, Butler A, Clarke O, Cole J, Dicks E, Dike A, Drozd A, Edwards K, Forbes S, Foster R, Gray K, Greenman C, Halliday K, Hills K, Kosmidou V, Lugg R, Menzies A, Perry J, Petty R, Raine K, Ratford L, Shepherd R, Small A, Stephens Y, Tofts C, Varian J, West S, Widaa S, Yates A, Brasseur F, Cooper CS, Flanagan AM, Knowles M, Leung SY, Louis DN, Looijenga LH, Malkowicz B, Pierotti MA, Teh B, Chenevix-Trench G, Weber BL, Yuen ST, Harris G, Goldstraw P, Nicholson AG, Futreal PA, Wooster R, Stratton MR (2004) Lung cancer: intragenic ERBB2 kinase mutations in tumours. Nature 431:525-5266
145. Stommel JM, Kimmelman AC, Ying H, Nabioullin R, Ponugoti AH, Wiedemeyer R, Stegh AH, Bradner JE, Ligon KL, Brennan C, Chin L, Depinho RA (2007) Coactivation of receptor tyrosine kinases affects the response of tumor cells to targeted therapies. Science 318:287-2900
146. Stratmann A, Risau W, Plate KH (1998) Cell type-specific expression of angiopoietin-1 and angiopoietin-2 suggests a role in glioblastoma angiogenesis. Am J Pathol 153:1459-14666
147. Surawska H, Ma PC, Salgia R (2004) The role of ephrins and Eph receptors in cancer. Cytokine Growth Factor Rev 15:419-4333
148. Tamura M, Gu J, Matsumoto K, Aota S, Parsons R, Yamada KM (1998) Inhibition of cell migration, spreading, and focal adhesions by tumor suppressor PTEN. Science 280:1614-16177
149. Thiessen B, Stewart C, Tsao M, Kamel-Reid S, Schaiquevich P, Mason W, Easaw J, Belanger K, Forsyth P, Mcintosh L, Eisenhauer E (2010) A phase I/II trial of GW572016 (lapatinib) in recurrent glioblastoma multiforme: clinical outcomes, pharmacokinetics and molecular correlation. Cancer Chemother Pharmacol 65:353-3611
150. Tokarski JS, Newitt JA, Chang CY, Cheng JD, Wittekind M, Kiefer SE, Kish K, Lee FY, Borzillerri R, Lombardo LJ, Xie D, Zhang Y, Klei HE (2006) The structure of Dasatinib (BMS-354825) bound to activated ABL kinase domain elucidates its inhibitory activity against imatinib-resistant ABL mutants. Cancer Res 66:5790-57977
151. Uhm JH, Ballman KV, Wu W, Giannini C, Krauss JC, Buckner JC, James CD, Scheithauer BW, Behrens RJ, Flynn PJ, Schaefer PL, Dakhill SR, Jaeckle KA (2011) Phase II evaluation of ge fitinib in patients with newly diagnosed Grade 4 astrocytoma: Mayo/North Central Cancer Treatment Group Study N0074. Int J Radiat Oncol Biol Phys 80:347-3533
152. Uhrbom L, Hesselager G, Nister M, Westermark B (1998) Induction of brain tumors in mice using a recombinant platelet-derived growth factor B-chain retrovirus. Cancer Res 58:5275-52799
153. Vajkoczy P, Knyazev P, Kunkel A, Capelle HH, Behrndt S, Von Tengg-Kobligk H, Kiessling F, Eichelsbacher U, Essig M, Read TA, Erber R, Ullrich A (2006) Dominant-negative inhibition of the Axl receptor tyrosine kinase suppresses brain tumor cell growth and invasion and prolongs survival. Proc Natl Acad Sci U S A 103:5799-58044
154. Valius M, Kazlauskas A (1993) Phospholipase C-gamma 1 and phosphatidylinositol 3 kinase are the downstream mediators of the PDGF receptor's mitogenic signal. Cell 73:321-3344
155. Van Den Bent MJ, Brandes AA, Rampling R, Kouwenhoven MC, Kros JM, Carpentier AF, Clement PM, Frenay M, Campone M, Baurain JF, Armand JP, Taphoorn MJ, Tosoni A, Kletzl H, Klughammer B, Lacombe D, Gorlia T (2009) Randomized phase II trial of erlotinib versus temozolomide or carmustine in recurrent glioblastoma: EORTC brain tumor group study 26034. J Clin Oncol 27:1268-12744
156. Varela M, Ranuncolo SM, Morand A, Lastiri J, De Kier Joffe EB, Puricelli LI, Pallotta MG (2004) EGF-R and PDGF-R, but not bcl-2, overexpression predict overall survival in patients with low-grade astrocytomas. J Surg Oncol 86:34-400
157. Verhaak RG, Hoadley KA, Purdom E, Wang V, Qi Y, Wilkerson MD, Miller CR, Ding L, Golub T, Mesirov JP, Alexe G, Lawrence M, O'kelly M, Tamayo P, Weir BA, Gabriel S, Winckler W, Gupta S, Jakkula L, Feiler HS, Hodgson JG, James CD, Sarkaria JN, Brennan C, Kahn A, Spellman PT, Wilson RK, Speed TP, Gray JW, Meyerson M, Getz G, Perou CM, Hayes DN (2010) Integrated genomic analysis identi fies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell 17:98-1100
158. Vogel W, Gish GD, Alves F, Pawson T (1997) The discoidin domain receptor tyrosine kinases are activated by collagen. Mol Cell 1:13-233
159. Vogel WF, Abdulhussein R, Ford CE (2006) Sensing extracellular matrix: an update on discoidin domain receptor function. Cell Signal 18:1108-11166
160. Wen PY (2010) American Society of Clinical Oncology 2010: report of selected studies from the CNS tumors section. Expert Rev Anticancer Ther 10:1367-13699
161. Wen PY, Yung WK, Lamborn KR, Dahia PL, Wang Y, Peng B, Abrey LE, Raizer J, Cloughesy TF, Fink K, Gilbert M, Chang S, Junck L, Schiff D, Lieberman F, Fine HA, Mehta M, Robins HI, Deangelis LM, Groves MD, Puduvalli VK, Levin V, Conrad C, Maher EA, Aldape K, Hayes M, Letvak L, Egorin MJ, Capdeville R, Kaplan R, Murgo AJ, Stiles C, Prados MD (2006) Phase I/II study of imatinib mesylate for recurrent malignant gliomas: North American Brain Tumor Consortium Study 99-08. Clin Cancer Res 12:4899-49077
162. Wilhelm SM, Carter C, Tang L, Wilkie D, Mcnabola A, Rong H, Chen C, Zhang X, Vincent P, Mchugh M, Cao Y, Shujath J, Gawlak S, Eveleigh D, Rowley B, Liu L, Adnane L, Lynch M, Auclair D, Taylor I, Gedrich R, Voznesensky A, Riedl B, Post LE, Bollag G, Trail PA (2004) BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res 64:7099-71099
163. Wimmer-Kleikamp SH, Lackmann M (2005) Eph-modulated cell morphology, adhesion and motility in carcinogenesis. IUBMB Life 57:421-4311
164. Wong AJ, Bigner SH, Bigner DD, Kinzler KW, Hamilton SR, Vogelstein B (1987) Increased expression of the epidermal growth factor receptor gene in malignant gliomas is invariably associated with gene amplification. Proc Natl Acad Sci U S A 84:6899-69033
165. Wykosky J, Gibo DM, Stanton C, Debinski W (2005) EphA2 as a novel molecular marker and target in glioblastoma multiforme. Mol Cancer Res 3:541-5511
166. Yakes FM, Chen J, Tan J, Yamaguchi K, Shi Y, Yu P, Qian F, Chu F, Bentzien F, Cancilla B, Orf J, You A, Laird AD, Engst S, Lee L, Lesch J, Chou YC, Joly A (2011) Cabozantinib (XL184), a novel MET and VEGFR2 inhibitor, simultaneously suppresses metastasis, angiogenesis, and tumor growth. Mol Cancer Ther 10:2298-23088
167. Yamada T, Tsubouchi H, Daikuhara Y, Prat M, Comoglio PM, Mcgeer PL, Mcgeer EG (1994) Immunohistochemistry with antibodies to hepatocyte growth factor and its receptor protein (c-MET) in human brain tissues. Brain Res 637:308-3122
168. Yamanaka R, Arao T, Yajima N, Tsuchiya N, Homma J, Tanaka R, Sano M, Oide A, Sekijima M, Nishio K (2006) Identification of expressed genes characterizing long-term survival in malignant glioma patients. Oncogene 25:5994-60022
169. Yamazaki H, Fukui Y, Ueyama Y, Tamaoki N, Kawamoto T, Taniguchi S, Shibuya M (1988) Ampli fication of the structurally and functionally altered epidermal growth factor receptor gene (c-erbB) in human brain tumors. Mol Cell Biol 8:1816-18200
170. Yarden Y, Sliwkowski MX (2001) Untangling the ErbB signalling network. Nat Rev Mol Cell Biol 2:127-1377
171. Ye K, Hurt KJ, Wu FY, Fang M, Luo HR, Hong JJ, Blackshaw S, Ferris CD, Snyder SH (2000) Pike. A nuclear gtpase that enhances PI3kinase activity and is regulated by protein 4.1 N. Cell 103:919-9300
172. Ye K, Aghdasi B, Luo HR, Moriarity JL, Wu FY, Hong JJ, Hurt KJ, Bae SS, Suh PG, Snyder SH (2002) Phospholipase C gamma 1 is a physiological guanine nucleotide exchange factor for the nuclear GTPase PIKE. Nature 415:541-5444
173. Yong HY, Kim IY, Kim JS, Moon A (2010) ErbB2-enhanced invasiveness of H-Ras MCF10A breast cells requires MMP-13 and uPA upregulation via p38 MAPK signaling. Int J Oncol 36:501-5077
174. Zadeh G, Koushan K, Pillo L, Shannon P, Guha A (2004a) Role of Ang1 and its interaction with VEGF-A in astrocytomas. J Neuropathol Exp Neurol 63:978-9899
175. Zadeh G, Qian B, Okhowat A, Sabha N, Kontos CD, Guha A (2004b) Targeting the Tie2/Tek receptor in astrocytomas. Am J Pathol 164:467-4766
176. Zadeh G, Koushan K, Baoping Q, Shannon P, Guha A (2010) Role of angiopoietin-2 in regulating growth and vascularity of astrocytomas. J Oncol 2010:6592311
177. Zeng Q, Chen S, You Z, Yang F, Carey TE, Saims D, Wang CY (2002) Hepatocyte growth factor inhibits anoikis in head and neck squamous cell carcinoma cells by activation of ERK and Akt signaling independent of NFkappa B. J Biol Chem 277:25203-252088
178. Zhang YW, Vande Woude GF (2003) HGF/SF-met signaling in the control of branching morphogenesis and invasion. J Cell Biochem 88:408-4177
179. Zhang QK, Boast S, De Los SK, Begemann M, Goff SP (1996) Transforming activity of retroviral genomes encoding Gag-Axl fusion proteins. J Virol 70:8089-80977
180. Zhang Z, Yang Y, Gong A, Wang C, Liang Y, Chen Y (2005) Localization of NGF and TrkA at mitotic apparatus in human glioma cell line U251. Biochem Biophys Res Commun 337:68-744