EphA receptor signaling-Complexity and emerging themes

Seminars in Cell and Developmental Biology

Volumn 23, Issue 1, 2012, Pages 16-25

  Miao, Hui ^a   Wang, Bingcheng ^a  

^a CASE WESTERN RESERVE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Cancer; Eph; Ephrin; Kinase; Signaling

Indexed keywords

DESMOGLEIN 1; EPHRIN A1; EPHRIN A3; EPHRIN A5; EPHRIN RECEPTOR; EPHRIN RECEPTOR A1; EPHRIN RECEPTOR A2; EPHRIN RECEPTOR A4; EPHRIN RECEPTOR B2; FOCAL ADHESION KINASE; GLIAL FIBRILLARY ACIDIC PROTEIN; GROWTH FACTOR RECEPTOR; INTEGRIN LINKED KINASE; MITOGEN ACTIVATED PROTEIN KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE 3; PAXILLIN; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE B; RAS PROTEIN; RHO GUANINE NUCLEOTIDE BINDING PROTEIN; UVOMORULIN;

CELL ADHESION; CELL GROWTH; CELL INTERACTION; CELL INVASION; CELL MIGRATION; CELL PROLIFERATION; CYTOSKELETON; DNA METHYLATION; DOWN REGULATION; EXTRACELLULAR MATRIX; GENE SILENCING; GLIOBLASTOMA; HEMATOLOGIC MALIGNANCY; HUMAN; MOLECULAR INTERACTION; NERVE FIBER; NONHUMAN; PROTEIN DEPHOSPHORYLATION; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; REVIEW; SCHWANN CELL; SIGNAL TRANSDUCTION; SKIN CANCER; TUMOR GROWTH; UPREGULATION;

EID: 84857439435     PISSN: 10849521     EISSN: 10963634     Source Type: Journal    
DOI: 10.1016/j.semcdb.2011.10.013     Document Type: Review

References (116)

1. Hirai H., Maru Y., Hagiwara K., Nishida J., Takaku F. A novel putative tyrosine kinase receptor encoded by the eph gene. Science 1987, 238:1717-1720.
2. Unified nomenclature for Eph family receptors and their ligands, the ephrins Eph Nomenclature Committee. Cell 1997, 90:403-404. Eph Nomenclature Committee, [letter, in process citation].
3. Bartley T.D., Hunt R.W., Welcher A.A., Boyle W.J., Parker V.P., Lindberg R.A., et al. B61 is a ligand for the ECK receptor protein-tyrosine kinase. Nature 1994, 368:558-560.
4. Cheng A., Diller D.J., Dixon S.L., Egan W.J., Lauri G., Merz K.M. Computation of the physio-chemical properties and data mining of large molecular collections 39. J Comput Chem 2002, 23:172-183.
5. Beckmann M.P., Cerretti D.P., Baum P., Vanden Bos T., James L., Farrah T., et al. Molecular characterization of a family of ligands for eph-related tyrosine kinase receptors. EMBO J 1994, 13:3757-3762.
6. Bergemann A.D., Zhang L., Chiang M.K., Brambilla R., Klein R., Flanagan J.G. Ephrin-B3, a ligand for the receptor EphB3, expressed at the midline of the developing neural tube. Oncogene 1998, 16:471-480.
7. Gale N.W., Flenniken A., Compton D.C., Jenkins N., Copeland N.G., Gilbert D.J., et al. Elk-L3, a novel transmembrane ligand for the Eph family of receptor tyrosine kinases, expressed in embryonic floor plate, roof plate and hindbrain segments. Oncogene 1996, 13:1343-1352.
8. Gale N.W., Holland S.J., Valenzuela D.M., Flenniken A., Pan L., Ryan T.E., et al. Eph receptors and ligands comprise two major specificity subclasses and are reciprocally compartmentalized during embryogenesis. Neuron 1996, 17:9-19.
9. Himanen J.P., Chumley M.J., Lackmann M., Li C., Barton W.A., Jeffrey P.D., et al. Repelling class discrimination: ephrin-A5 binds to and activates EphB2 receptor signaling. Nat Neurosci 2004, 7:501-509.
10. Adams R.H., Klein R. Eph receptors and ephrin ligands. Essential mediators of vascular development. Trends Cardiovasc Med 2000, 10:183-188.
11. Flanagan J.G., Vanderhaeghen P. The ephrins and Eph receptors in neural development. Annu Rev Neurosci 1998, 21:309-345.
12. Pasquale E.B. Eph receptor signalling casts a wide net on cell behaviour. Nat Rev Mol Cell Biol 2005, 6:462-475.
13. Miao H., Wang B. Eph/ephrin signaling in epithelial development and homeostasis. Int J Biochem Cell Biol 2009, 41:762-770.
14. Hafner C., Schmitz G., Meyer S., Bataille F., Hau P., Langmann T., et al. Differential gene expression of Eph receptors and ephrins in benign human tissues and cancers. Clin Chem 2004, 50:490-499.
15. Flanagan J.G. Neural map specification by gradients. Curr Opin Neurobiol 2006, 16:59-66.
16. Himanen J.P., Saha N., Nikolov D.B. Cell-cell signaling via Eph receptors and ephrins. Curr Opin Cell Biol 2007, 19:534-542.
17. Klein R. Eph/ephrin signaling in morphogenesis, neural development and plasticity. Curr Opin Cell Biol 2004, 16:580-589.
18. Kullander K., Klein R. Mechanisms and functions of Eph and ephrin signalling 2. Nat Rev Mol Cell Biol 2002, 3:475-486.
19. Lackmann M., Boyd A.W. Eph, a protein family coming of age: more confusion, insight, or complexity?. Sci Signal 2008, 1:re2.
20. Miao H., Wang B. Eph/ephrin signaling in epithelial development and homeostasis. Int J Biochem Cell Biol 2008, 41:762-770.
21. Pasquale E.B. Eph receptors and ephrins in cancer: bidirectional signalling and beyond. Nat Rev Cancer 2010, 10:165-180.
22. Arvanitis D., Davy A. Eph/ephrin signaling: networks. Genes Dev 2008, 22:416-429.
23. Pasquale E.B. Eph-ephrin bidirectional signaling in physiology and disease. Cell 2008, 133:38-52.
24. Zou J.X., Wang B., Kalo M.S., Zisch A.H., Pasquale E.B., Ruoslahti E. An Eph receptor regulates integrin activity through R-Ras. Proc Natl Acad Sci USA 1999, 96:13813-13818.
25. Miao H., Burnett E., Kinch M., Simon E., Wang B. Activation of EphA2 kinase suppresses integrin function and causes focal-adhesion-kinase dephosphorylation. Nat Cell Biol 2000, 2:62-69.
26. Gopal U., Bohonowych J.E., Lema-Tome C., Liu A., Garrett-Mayer E., Wang B., et al. A novel extracellular Hsp90 mediated co-receptor function for LRP1 regulates EphA2 dependent glioblastoma cell invasion. PLoS One 2011, 6:e17649.
27. Astin J.W., Batson J., Kadir S., Charlet J., Persad R.A., Gillatt D., et al. Competition amongst Eph receptors regulates contact inhibition of locomotion and invasiveness in prostate cancer cells. Nat Cell Biol 2010, 12:1194-1204.
28. Bourgin C., Murai K.K., Richter M., Pasquale E.B. The EphA4 receptor regulates dendritic spine remodeling by affecting beta1-integrin signaling pathways. J Cell Biol 2007, 178:1295-1307.
29. Yamazaki T., Masuda J., Omori T., Usui R., Akiyama H., Maru Y. EphA1 interacts with integrin-linked kinase and regulates cell morphology and motility. J Cell Sci 2009, 122:243-255.
30. Gu C., Park S. The EphA8 receptor regulates integrin activity through p110gamma phosphatidylinositol-3 kinase in a tyrosine kinase activity-independent manner. Mol Cell Biol 2001, 21:4579-4597.
31. Walsh R., Blumenberg M. Specific and shared targets of ephrin A signaling in epidermal keratinocytes. J Biol Chem 2011, 286:9419-9428.
32. Afshari F.T., Kwok J.C., Fawcett J.W. Astrocyte-produced ephrins inhibit schwann cell migration via VAV2 signaling. J Neurosci 2010, 30:4246-4255.
33. Davy A., Robbins S.M. Ephrin-A5 modulates cell adhesion and morphology in an integrin-dependent manner. EMBO J 2000, 19:5396-5405.
34. Huai J., Drescher U. An ephrin-A-dependent signaling pathway controls integrin function and is linked to the tyrosine phosphorylation of a 120-kDa protein. J Biol Chem 2001, 276:6689-6694.
35. Ting M.J., Day B.W., Spanevello M.D., Boyd A.W. Activation of ephrin A proteins influences hematopoietic stem cell adhesion and trafficking patterns. Exp Hematol 2010, 38:1087-1098.
36. Sharfe N., Nikolic M., Cimpeon L., Van De Kratts A., Freywald A., Roifman C.M. EphA and ephrin-A proteins regulate integrin-mediated T lymphocyte interactions. Mol Immunol 2008, 45:1208-1220.
37. Tanaka M., Kamata R., Sakai R. EphA2 phosphorylates the cytoplasmic tail of Claudin-4 and mediates paracellular permeability. J Biol Chem 2005, 280:42375-42382.
38. Buchert M., Schneider S., Meskenaite V., Adams M.T., Canaani E., Baechi T., et al. The junction-associated protein AF-6 interacts and clusters with specific Eph receptor tyrosine kinases at specialized sites of cell-cell contact in the brain. J Cell Biol 1999, 144:361-371.
39. Miura K., Nam J.M., Kojima C., Mochizuki N., Sabe H. EphA2 engages Git1 to suppress Arf6 activity modulating epithelial cell-cell contacts. Mol Biol Cell 2009, 20:1949-1959.
40. Orsulic S., Kemler R. Expression of Eph receptors and ephrins is differentially regulated by E-cadherin. J Cell Sci 2000, 113(Pt 10):1793-1802.
41. Zantek N.D., Azimi M., Fedor-Chaiken M., Wang B., Brackenbury R., Kinch M.S. E-cadherin regulates the function of the EphA2 receptor tyrosine kinase. Cell Growth Differ 1999, 10:629-638. [in process citation].
42. Lin S., Gordon K., Kaplan N., Getsios S. Ligand targeting of EphA2 enhances keratinocyte adhesion and differentiation via desmoglein 1. Mol Biol Cell 2010, 21:3902-3914.
43. Guo H., Miao H., Gerber L., Singh J., Denning M.F., Gilliam A.C., et al. Disruption of EphA2 receptor tyrosine kinase leads to increased susceptibility to carcinogenesis in mouse skin. Cancer Res 2006, 66:7050-7058.
44. Jun G., Guo H., Klein B.E.K., Klein R., Wang J.J., Mitchell P., et al. EPHA2 is associated with age-related cortical cataract in mice and humans. PLoS Genet 2009, 5:e1000584.
45. Cooper M.A., Son A.I., Komlos D., Sun Y., Kleiman N.J., Zhou R. Loss of ephrin-A5 function disrupts lens fiber cell packing and leads to cataract. Proc Natl Acad Sci USA 2008, 105:16620-16625.
46. Tan W., Hou S., Jiang Z., Hu Z., Yang P., Ye J. Association of EPHA2 polymorphisms and age-related cortical cataract in a Han Chinese population. Mol Vis 2011, 17:1553-1558.
47. Kaul H., Riazuddin S.A., Shahid M., Kousar S., Butt N.H., Zafar A.U., et al. Autosomal recessive congenital cataract linked to EPHA2 in a consanguineous Pakistani family. Mol Vis 2010, 16:511-517.
48. Zhang T., Hua R., Xiao W., Burdon K.P., Bhattacharya S.S., Craig J.E., et al. Mutations of the EPHA2 receptor tyrosine kinase gene cause autosomal dominant congenital cataract. Hum Mutat 2009, 30:E603-E611.
49. Shiels A., Bennett T.M., Knopf H.L., Maraini G., Li A., Jiao X., et al. The EPHA2 gene is associated with cataracts linked to chromosome 1p. Mol Vis 2008, 14:2042-2055.
50. Cowan C.W., Shao Y.R., Sahin M., Shamah S.M., Lin M.Z., Greer P.L., et al. Vav family GEFs link activated Ephs to endocytosis and axon guidance. Neuron 2005, 46:205-217.
51. Sahin M., Greer P.L., Lin M.Z., Poucher H., Eberhart J., Schmidt S., et al. Eph-dependent tyrosine phosphorylation of ephexin1 modulates growth cone collapse. Neuron 2005, 46:191-204.
52. Shi L., Fu W.Y., Hung K.W., Porchetta C., Hall C., Fu A.K., et al. Alpha2-chimaerin interacts with EphA4 and regulates EphA4-dependent growth cone collapse. Proc Natl Acad Sci USA 2007, 104:16347-16352.
53. Takeuchi S., Yamaki N., Iwasato T., Negishi M., Katoh H. Beta2-chimaerin binds to EphA receptors and regulates cell migration. FEBS Lett 2009, 583:1237-1242.
54. Wegmeyer H., Egea J., Rabe N., Gezelius H., Filosa A., Enjin A., et al. EphA4-dependent axon guidance is mediated by the RacGAP alpha2-chimaerin. Neuron 2007, 55:756-767.
55. Tanaka M., Ohashi R., Nakamura R., Shinmura K., Kamo T., Sakai R., et al. Tiam1 mediates neurite outgrowth induced by ephrin-B1 and EphA2. EMBO J 2004, 23:1075-1088.
56. Hiramoto-Yamaki N., Takeuchi S., Ueda S., Harada K., Fujimoto S., Negishi M., et al. Ephexin4 and EphA2 mediate cell migration through a RhoG-dependent mechanism. J Cell Biol 2010, 190:461-477.
57. Harada K., Hiramoto-Yamaki N., Negishi M., Katoh H. Ephexin4 and EphA2 mediate resistance to anoikis through RhoG and phosphatidylinositol 3-kinase. Exp Cell Res 2011, 317:1701-1713.
58. Fabes J., Anderson P., Yanez-Munoz R.J., Thrasher A., Brennan C., Bolsover S. Accumulation of the inhibitory receptor EphA4 may prevent regeneration of corticospinal tract axons following lesion. Eur J Neurosci 2006, 23:1721-1730.
59. Goldshmit Y., McLenachan S., Turnley A. Roles of Eph receptors and ephrins in the normal and damaged adult CNS. Brain Res Rev 2006, 52:327-345.
60. Puschmann T.B., Turnley A.M. Eph receptor tyrosine kinases regulate astrocyte cytoskeletal rearrangement and focal adhesion formation. J Neurochem 2010, 113:881-894.
61. Cheng Q., Sasaki Y., Shoji M., Sugiyama Y., Tanaka H., Nakayama T., et al. Cdk5/p35 and Rho-kinase mediate ephrin-A5-induced signaling in retinal ganglion cells. Mol Cell Neurosci 2003, 24:632-645.
62. Nie D., Di N.A., Han J.M., Baharanyi H., Kramvis I., Huynh T., et al. Tsc2-Rheb signaling regulates EphA-mediated axon guidance. Nat Neurosci 2010, 13:163-172.
63. Miao H., Wei B.R., Peehl D.M., Li Q., Alexandrou T., Schelling J.R., et al. Activation of EphA receptor tyrosine kinase inhibits the Ras/MAPK pathway. Nat Cell Biol 2001, 3:527-530.
64. Batlle E., Bacani J., Begthel H., Jonkeer S., Gregorieff A., van de B.M., et al. EphB receptor activity suppresses colorectal cancer progression. Nature 2005, 435:1126-1130.
65. Noren N.K., Foos G., Hauser C.A., Pasquale E.B. The EphB4 receptor suppresses breast cancer cell tumorigenicity through an Abl-Crk pathway. Nat Cell Biol 2006, 8:815-825.
66. Brantley-Sieders D.M., Zhuang G., Hicks D., Fang W.B., Hwang Y., Cates J.M., et al. The receptor tyrosine kinase EphA2 promotes mammary adenocarcinoma tumorigenesis and metastatic progression in mice by amplifying ErbB2 signaling. J Clin Invest 2008, 118:64-78.
67. Fukai J., Yokote H., Yamanaka R., Arao T., Nishio K., Itakura T. EphA4 promotes cell proliferation and migration through a novel EphA4-FGFR1 signaling pathway in the human glioma U251 cell line. Mol Cancer Ther 2008, 7:2768-2778.
68. Miao H., Li D.-Q., Mukherjee A., Guo H., Petty A., Basilion J., et al. EphA2 mediates ligand-dependent inhibition and ligand-independent promotion of cell migration and invasion via a reciprocal regulatory loop with Akt. Cancer Cell 2009, 16:9-20.
69. Smith L.M., Walsh P.T., Rudiger T., Cotter T.G., Mc Carthy T.V., Marx A., et al. EphA3 is induced by CD28 and IGF-1 and regulates cell adhesion. Exp Cell Res 2004, 292:295-303.
70. Macrae M., Neve R.M., Rodriguez-Viciana P., Haqq C., Yeh J., Chen C., et al. A conditional feedback loop regulates Ras activity through EphA2. Cancer Cell 2005, 8:111-118.
71. Miao H., Nickel C.H., Cantley L.G., Bruggeman L.A., Bennardo L.N., Wang B. EphA kinase activation regulates HGF-induced epithelial branching morphogenesis. J Cell Biol 2003, 162:1281-1292.
72. Yang N.Y., Fernandez C., Richter M., Xiao Z., Valencia F., Tice D.A., et al. Crosstalk of the EphA2 receptor with a serine/threonine phosphatase suppresses the Akt-mTORC1 pathway in cancer cells. Cell Signal 2011, 23:201-212.
73. Tong J., Elowe S., Nash P., Pawson T. Manipulation of EphB2 regulatory motifs and SH2 binding sites switches MAPK signaling and biological activity. J Biol Chem 2003, 278:6111-6119.
74. Park E.K., Warner N., Bong Y.S., Stapleton D., Maeda R., Pawson T., et al. Ectopic EphA4 receptor induces posterior protrusions via FGF signaling in Xenopus embryos. Mol Biol Cell 2004, 15:1647-1655.
75. Li J.J., Liu D.P., Liu G.T., Xie D. EphrinA5 acts as a tumor suppressor in glioma by negative regulation of epidermal growth factor receptor. Oncogene 2009, 28:1759-1768.
76. Marler K.J., Becker-Barroso E., Martinez A., Llovera M., Wentzel C., Poopalasundaram S., et al. A TrkB/EphrinA interaction controls retinal axon branching and synaptogenesis. J Neurosci 2008, 28:12700-12712.
77. Brisbin S., Liu J., Boudreau J., Peng J., Evangelista M., Chin-Sang I. A role for C. elegans Eph RTK signaling in PTEN regulation. Dev Cell 2009, 17:459-469.
78. Chiarugi P., Taddei M.L., Schiavone N., Papucci L., Giannoni E., Fiaschi T., et al. LMW-PTP is a positive regulator of tumor onset and growth. Oncogene 2004, 23:3905-3914.
79. Kikawa K.D., Vidale D.R., Van Etten R.L., Kinch M.S. Regulation of the EphA2 kinase by the low molecular weight tyrosine phosphatase induces transformation. J Biol Chem 2002, 277:39274-39279.
80. Nievergall E., Janes P.W., Stegmayer C., Vail M.E., Haj F.G., Teng S.W., et al. PTP1B regulates Eph receptor function and trafficking. J Cell Biol 2010, 191:1189-1203.
81. Shintani T., Ihara M., Sakuta H., Takahashi H., Watakabe I., Noda M. Eph receptors are negatively controlled by protein tyrosine phosphatase receptor type O. Nat Neurosci 2006.
82. Wimmer-Kleikamp S.H., Nievergall E., Gegenbauer K., Adikari S., Mansour M., Yeadon T., et al. Elevated protein tyrosine phosphatase activity provokes Eph/ephrin-facilitated adhesion of pre-B leukemia cells. Blood 2008, 112:721-732.
83. Zhuang G., Hunter S., Hwang Y., Chen J. Regulation of EphA2 receptor endocytosis by SHIP2 lipid phosphatase via phosphatidylinositol 3-kinase-dependent Rac1 activation. J Biol Chem 2007, 282:2683-2694.
84. Zelinski D.P., Zantek N.D., Stewart J.C., Irizarry A.R., Kinch M.S. EphA2 overexpression causes tumorigenesis of mammary epithelial cells. Cancer Res 2001, 61:2301-2306.
85. Coulthard M.G., Lickliter J.D., Subanesan N., Chen K., Webb G.C., Lowry A.J., et al. Characterization of the Epha1 receptor tyrosine kinase: expression in epithelial tissues. Growth Factors 2001, 18:303-317.
86. Fox B.P., Kandpal R.P. Invasiveness of breast carcinoma cells and transcript profile: Eph receptors and ephrin ligands as molecular markers of potential diagnostic and prognostic application. Biochem Biophys Res Commun 2004, 318:882-892.
87. Herath N.I., Spanevello M.D., Sabesan S., Newton T., Cummings M., Duffy S., et al. Over-expression of Eph and ephrin genes in advanced ovarian cancer: ephrin gene expression correlates with shortened survival. BMC Cancer 2006, 6:144.
88. Dodelet V.C., Pasquale E.B. Eph receptors and ephrin ligands: embryogenesis to tumorigenesis. Oncogene 2000, 19:5614-5619. [in process citation].
89. Ireton R.C., Chen J. EphA2 receptor tyrosine kinase as a promising target for cancer therapeutics. Curr Cancer Drug Targets 2005, 5:149-157.
90. Nakamoto M., Bergemann A.D. Diverse roles for the Eph family of receptor tyrosine kinases in carcinogenesis. Microsc Res Tech 2002, 59:58-67.
91. Miyazaki T., Kato H., Fukuchi M., Nakajima M., Kuwano H. EphA2 overexpression correlates with poor prognosis in esophageal squamous cell carcinoma. Int J Cancer 2003, 103:657-663.
92. Saito T., Masuda N., Miyazaki T., Kanoh K., Suzuki H., Shimura T., et al. Expression of EphA2 and E-cadherin in colorectal cancer: correlation with cancer metastasis. Oncol Rep 2004, 11:605-611.
93. Fang W.B., Brantley-Sieders D.M., Parker M.A., Reith A.D., Chen J. A kinase-dependent role for EphA2 receptor in promoting tumor growth and metastasis. Oncogene 2005, 7859-7868.
94. Wykosky J., Gibo D.M., Stanton C., Debinski W. EphA2 as a novel molecular marker and target in glioblastoma multiforme. Mol Cancer Res 2005, 3:541-551.
95. Parri M., Buricchi F., Giannoni E., Grimaldi G., Mello T., Raugei G., et al. EphrinA1 activates a Src/focal adhesion kinase-mediated motility response leading to rho-dependent actino/myosin contractility. J Biol Chem 2007, 282:19619-19628.
96. Wang B. Cancer cells exploit the eph-ephrin system to promote invasion and metastasis: tales of unwitting partners. Sci Signal 2011, 4:e28.
97. Bae H.J., Song J.H., Noh J.H., Kim J.K., Jung K.H., Eun J.W., et al. Low frequency mutation of the Ephrin receptor A3 gene in hepatocellular carcinoma. Neoplasma 2009, 56:331-334.
98. Balakrishnan A., Bleeker F.E., Lamba S., Rodolfo M., Daniotti M., Scarpa A., et al. Novel somatic and germline mutations in cancer candidate genes in glioblastoma, melanoma, and pancreatic carcinoma. Cancer Res 2007, 67:3545-3550.
99. Bonifaci N., Gorski B., Masojc B., Wokolorczyk D., Jakubowska A., Debniak T., et al. Exploring the link between germline and somatic genetic alterations in breast carcinogenesis. PLoS One 2010, 5:e14078.
100. Ding L., Getz G., Wheeler D.A., Mardis E.R., McLellan M.D., Cibulskis K., et al. Somatic mutations affect key pathways in lung adenocarcinoma. Nature 2008, 455:1069-1075.
101. Oshima T., Akaike M., Yoshihara K., Shiozawa M., Yamamoto N., Sato T., et al. Overexpression of EphA4 gene and reduced expression of EphB2 gene correlates with liver metastasis in colorectal cancer. Int J Oncol 2008, 33:573-577.
102. Fu D.Y., Wang Z.M., Wang B.L., Chen L., Yang W.T., Shen Z.Z., et al. Frequent epigenetic inactivation of the receptor tyrosine kinase EphA5 by promoter methylation in human breast cancer. Hum Pathol 2010, 41:48-58.
103. Guan M., Xu C., Zhang F., Ye C. Aberrant methylation of EphA7 in human prostate cancer and its relation to clinicopathologic features. Int J Cancer 2009, 124:88-94.
104. Morrissey C., True L.D., Roudier M.P., Coleman I.M., Hawley S., Nelson P.S., et al. Differential expression of angiogenesis associated genes in prostate cancer bone, liver and lymph node metastases. Clin Exp Metastasis 2008, 25:377-388.
105. Zhang W., Zeng X., Briggs K.J., Beaty R., Simons B., Chiu Yen R.W., et al. A potential tumor suppressor role for Hic1 in breast cancer through transcriptional repression of ephrin-A1. Oncogene 2010, 29:2467-2476.
106. Shi L., Itoh F., Itoh S., Takahashi S., Yamamoto M., Kato M. Ephrin-A1 promotes the malignant progression of intestinal tumors in Apc(min/+) mice. Oncogene 2008, 27:3265-3273.
107. Li X., Wang L., Gu J.W., Li B., Liu W.P., Wang Y.G., et al. Up-regulation of EphA2 and down-regulation of EphrinA1 are associated with the aggressive phenotype and poor prognosis of malignant glioma. Tumour Biol 2010, 31:477-488.
108. Almog N., Ma L., Raychowdhury R., Schwager C., Erber R., Short S., et al. Transcriptional switch of dormant tumors to fast-growing angiogenic phenotype. Cancer Res 2009, 69:836-844.
109. Bruce V., Olivieri G., Eickelberg O., Miescher G.C. Functional activation of EphA5 receptor does not promote cell proliferation in the aberrant EphA5 expressing human glioblastoma U-118 MG cell line. Brain Res 1999, 821:169-176.
110. Sharfe N., Freywald A., Toro A., Dadi H., Roifman C. Ephrin stimulation modulates T cell chemotaxis. Eur J Immunol 2002, 32:3745-3755.
111. Aasheim H.C., Delabie J., Finne E.F. Ephrin-A1 binding to CD4+ T lymphocytes stimulates migration and induces tyrosine phosphorylation of PYK2. Blood 2005, 105:2869-2876.
112. de Saint-Vis B., Bouchet C., Gautier G., Valladeau J., Caux C., Garrone P. Human dendritic cells express neuronal Eph receptor tyrosine kinases: role of EphA2 in regulating adhesion to fibronectin. Blood 2003, 102:4431-4440.
113. Kuang S.Q., Bai H., Fang Z.H., Lopez G., Yang H., Tong W., et al. Aberrant DNA methylation and epigenetic inactivation of Eph receptor tyrosine kinases and ephrin ligands in acute lymphoblastic leukemia. Blood 2010, 115:2412-2419.
114. Trinidad E.M., Zapata A.G., Alonso-Colmenar L.M. Eph-ephrin bidirectional signaling comes into the context of lymphocyte transendothelial migration. Cell Adhes Migr 2010, 4:363-367.
115. Udayakumar D., Zhang G., Ji Z., Njauw C.N., Mroz P., Tsao H. Epha2 is a critical oncogene in melanoma. Oncogene 2011, doi:10.1038/onc.2011.210 [Epub ahead of print].
116. Noren N.K., Yang N.Y., Silldorff M., Mutyala R., Pasquale E.B. Ephrin-independent regulation of cell substrate adhesion by the EphB4 receptor. Biochem J 2009, 422:433-442.