The multifaceted roles of Eph-ephrin signaling in breast cancer

Cell Adhesion and Migration

Volumn 6, Issue 2, 2012, Pages 138-147

  Kaenel, Philip ^a   Mosimann, Mischa ^a   Andres, Anne Catherine ^a  

^a UNIVERSITY OF BERN   (Switzerland)

Author keywords

Angiogenesis; Differentiation; EphA; EphB; Mammary gland; Stem cells; Tumorigenesis

Indexed keywords

ANGIOGENIC FACTOR; CYCLIN D1; EPHRIN; EPHRIN B2; EPHRIN RECEPTOR; EPHRIN RECEPTOR A2; EPHRIN RECEPTOR A4; EPHRIN RECEPTOR B6; ESTROGEN; PROGESTERONE; PROLACTIN; TRASTUZUMAB; TUMOR SUPPRESSOR PROTEIN; UVOMORULIN;

ANGIOGENESIS; ANTINEOPLASTIC ACTIVITY; BREAST; BREAST CANCER; BREAST CARCINOGENESIS; BREAST EPITHELIUM; BREAST METASTASIS; CANCER CELL CULTURE; CANCER GROWTH; CANCER LOCALIZATION; CANCER STEM CELL; CELL ADHESION; CELL DIFFERENTIATION; CELL FATE; CELL PROLIFERATION; CELL VIABILITY; ESTROGEN BLOOD LEVEL; FLUORESCENCE ACTIVATED CELL SORTING; GENE EXPRESSION; GENE EXPRESSION PROFILING; GENE OVEREXPRESSION; HISTOPATHOLOGY; HOMEOSTASIS; HUMAN; IN VITRO STUDY; IN VIVO STUDY; MAMMARY GLAND; NONHUMAN; PROGESTERONE BLOOD LEVEL; PROLACTIN BLOOD LEVEL; PROMOTER REGION; PROTEIN FUNCTION; PROTEIN LOCALIZATION; PROTEIN PHOSPHORYLATION; PROTEIN PROTEIN INTERACTION; PROTEIN SYNTHESIS; RECEPTOR DOWN REGULATION; REVIEW; SIGNAL TRANSDUCTION; STEM CELL; TUMOR SUPPRESSOR GENE; TUMOR XENOGRAFT;

EID: 84863890486     PISSN: 19336918     EISSN: 19336926     Source Type: Journal    
DOI: 10.4161/cam.20154     Document Type: Review

References (79)

1. Pasquale EB. Eph-ephrin bidirectional signaling in physiology and disease. Cell 2008; 133:38-52; PMID: 18394988; http://dx.doi.org/10.1016/j.cell. 2008.03.011
2. Lim YS, McLaughlin T, Sung TC, Santiago A, Lee KF, O'Leary DD. p75(NTR) mediates ephrin-A reverse signaling required for axon repulsion and mapping. Neuron 2008; 59:746-58; PMID:18786358; http://dx.doi.org/10.1016/j.neuron.2008. 07.032
3. Janes PW, Griesshaber B, Atapattu L, Nievergall E, Hii LL, Mensinga A, et al. Eph receptor function is modulated by heterooligomerization of A and B type Eph receptors. J Cell Biol 2011; 195:1033-45; PMID: 22144690; http://dx.doi.org/10.1083/jcb.201104037
4. Solanas G, Batlle E. Control of cell adhesion and compartmentalization in the intestinal epithelium. Exp Cell Res 2011; 317:2695-701; PMID:21820431; http://dx.doi.org/10.1016/j.yexcr.2011.07.019
5. Arvanitis D, Davy A. Eph/ephrin signaling: networks. Genes Dev 2008; 22:416-29; PMID:18281458; http://dx.doi.org/10.1101/gad.1630408
6. Orsulic S, Kemler R. Expression of Eph receptors and ephrins is differentially regulated by E-cadherin. J Cell Sci 2000; 113:1793-802; PMID:10769210
7. Cortina C, Palomo-Ponce S, Iglesias M, Fernández-Masip JL, Vivancos A, Whissell G, et al. EphB-ephrin-B interactions suppress colorectal cancer progression by compartmentalizing tumor cells. Nat Genet 2007; 39:1376-83; PMID:17906625; http://dx.doi.org/10.1038/ng.2007.11
8. Larsen AB, Pedersen MW, Stockhausen MT, Grandal MV, van Deurs B, Poulsen HS. Activation of the EGFR gene target EphA2 inhibits epidermal growth factor-induced cancer cell motility. Mol Cancer Res 2007; 5:283-93; PMID:17374733; http://dx.doi.org/10.1158/1541-7786.MCR-06-0321
9. 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; 190:461-77; PMID: 20679435; http://dx.doi.org/10. 1083/jcb.201005141
10. Zhuang G, Brantley-Sieders DM, Vaught D, Yu J, Xie L, Wells S, et al. Elevation of receptor tyrosine kinase EphA2 mediates resistance to trastuzumab therapy. Cancer Res 2010; 70:299-308; PMID:20028874; http://dx.doi.org/10.1158/ 0008-5472.CAN-09-1845
11. Kashyap AS, Hollier BG, Manton KJ, Satyamoorthy K, Leavesley DI, Upton Z. Insulin-like growth factor-I: vitronectin complex-induced changes in gene expression effect breast cell survival and migration. Endocrinology 2011; 152:1388-401; PMID: 21303956; http://dx.doi.org/10.1210/en.2010-0897
12. Qiu R, Wang J, Tsark W, Lu Q. Essential role of PDZRGS3 in the maintenance of neural progenitor cells. Stem Cells 2010; 28:1602-10; PMID:20629178; http://dx.doi.org/10.1002/stem.478
13. Essmann CL, Martinez E, Geiger JC, Zimmer M, Traut MH, Stein V, et al. Serine phosphorylation of ephrinB2 regulates trafficking of synaptic AMPA receptors. Nat Neurosci 2008; 11:1035-43; PMID: 19160501; http://dx.doi.org/10. 1038/nn.2171
14. Klein R. Bidirectional modulation of synaptic functions by Eph/ephrin signaling. Nat Neurosci 2009; 12:15-20; PMID:19029886; http://dx.doi.org/10. 1038/nn.2231
15. Noblitt LW, Bangari DS, Shukla S, Knapp DW, Mohammed S, Kinch MS, et al. Decreased tumorigenic potential of EphA2-overexpressing breast cancer cells following treatment with adenoviral vectors that express EphrinA1. Cancer Gene Ther 2004; 11:757-66; PMID: 15359289; http://dx.doi.org/10.1038/sj.cgt.7700761
16. Macrae M, Neve RM, Rodriguez-Viciana P, Haqq C, Yeh J, Chen C, et al. A conditional feedback loop regulates Ras activity through EphA2. Cancer Cell 2005; 8:111-8; PMID:16098464; http://dx.doi.org/10.1016/j.ccr.2005.07.005
17. Yang NY, Fernandez C, Richter M, Xiao Z, Valencia F, Tice DA, et al. Crosstalk of the EphA2 receptor with a serine/threonine phosphatase suppresses the Aktm-TORC1 pathway in cancer cells. Cell Signal 2011; 23:201-12; PMID:20837138; http://dx.doi.org/10.1016/j.cellsig.2010.09.004
18. Carles-Kinch K, Kilpatrick KE, Stewart JC, Kinch MS. Antibody targeting of the EphA2 tyrosine kinase inhibits malignant cell behavior. Cancer Res 2002; 62:2840-7; PMID:12019162
19. Fu DY, Wang ZM, Wang BL, Chen L, Yang WT, Shen ZZ, et al. Frequent epigenetic inactivation of the receptor tyrosine kinase EphA5 by promoter methylation in human breast cancer. Hum Pathol 2010; 41:48-58; PMID:19733895; http://dx.doi.org/10.1016/j.humpath.2009.06.007
20. Noren NK, Foos G, Hauser CA, Pasquale EB. The EphB4 receptor suppresses breast cancer cell tumor-igenicity through an Abl-Crk pathway. Nat Cell Biol 2006; 8:815-25; PMID:16862147; http://dx.doi.org/10.1038/ncb1438
21. Berclaz G, Flütsch B, Altermatt HJ, Rohrbach V, Djonov V, Ziemiecki A, et al. Loss of EphB4 receptor tyrosine kinase protein expression during carcinogenesis of the human breast. Oncol Rep 2002; 9:985-9; PMID:12168060
22. Truitt L, Freywald A. Dancing with the dead: Eph receptors and their kinase-null partners. Biochem Cell Biol 2011; 89:115-29; PMID:21455264; http://dx.doi.org/10.1139/O10-145
23. Fox BP, Kandpal RP. A paradigm shift in EPH receptor interaction: biological relevance of EPHB6 interaction with EPHA2 and EPHB2 in breast carcinoma cell lines. Cancer Genomics Proteomics 2011; 8:185-93; PMID: 21737611
24. Fox BP, Kandpal RP. 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; 318:882-92; PMID:15147954; http://dx.doi.org/10.1016/j.bbrc.2004.04.102
25. Fox BP, Kandpal RP. EphB6 receptor significantly alters invasiveness and other phenotypic characteristics of human breast carcinoma cells. Oncogene 2009; 28:1706-13; PMID:19234485; http://dx.doi.org/10.1038/onc.2009.18
26. Fox BP, Kandpal RP. Transcriptional silencing of EphB6 receptor tyrosine kinase in invasive breast carcinoma cells and detection of methylated promoter by methylation specific PCR. Biochem Biophys Res Commun 2006; 340:268-76; PMID:16364251; http://dx.doi.org/10.1016/j.bbrc.2005.11.174
27. Truitt L, Freywald T, DeCoteau J, Sharfe N, Freywald A. The EphB6 receptor cooperates with c-Cbl to regulate the behavior of breast cancer cells. Cancer Res 2010; 70:1141-53; PMID:20086179; http://dx.doi.org/10.1158/0008-5472. CAN-09-1710
28. Wu Q, Suo Z, Risberg B, Karlsson MG, Villman K, Nesland JM. Expression of Ephb2 and Ephb4 in breast carcinoma. Pathol Oncol Res 2004; 10:26-33; PMID: 15029258; http://dx.doi.org/10.1007/BF02893405
29. Brantley-Sieders DM, Jiang A, Sarma K, Badu-Nkansah A, Walter DL, Shyr Y, et al. Eph/ephrin profiling in human breast cancer reveals significant associations between expression level and clinical outcome. PLoS One 2011; 6:e24426; PMID:21935409; http://dx.doi.org/10.1371/journal.pone.0024426
30. Ogawa K, Pasqualini R, Lindberg RA, Kain R, Freeman AL, Pasquale EB. The ephrin-A1 ligand and its receptor, EphA2, are expressed during tumor neovascularization. Oncogene 2000; 19:6043-52; PMID: 11146556; http://dx.doi.org/10.1038/sj.onc.1204004
31. Zelinski DP, Zantek ND, Stewart JC, Irizarry AR, Kinch MS. EphA2 overexpression causes tumorigenesis of mammary epithelial cells. Cancer Res 2001; 61:2301-6; PMID:11280802
32. Pan M. Over-expression of EphA2 gene in invasive breast cancer and its association with hormone receptor status. J Clin Oncol 2005; 23:9583.
33. Fang WB, Brantley-Sieders DM, Parker MA, Reith AD, Chen J. A kinase-dependent role for EphA2 receptor in promoting tumor growth and metastasis. Oncogene 2005; 24:7859-68; PMID:16103880; http://dx.doi.org/10.1038/ sj.onc.1208937
34. Brantley-Sieders DM, Zhuang G, Hicks D, Fang WB, Hwang Y, Cates JM, et al. The receptor tyrosine kinase EphA2 promotes mammary adenocarcinoma tumor-igenesis and metastatic progression in mice by amplifying ErbB2 signaling. J Clin Invest 2008; 118:64-78; PMID:18079969; http://dx.doi.org/10.1172/ JCI33154
35. Landen CN, Merritt WM, Mangala LS, Sanguino AM, Bucana C, Lu C, et al. Intraperitoneal delivery of liposomal siRNA for therapy of advanced ovarian cancer. Cancer Biol Ther 2006; 5:1708-13; PMID: 17106249; http://dx.doi.org/10. 4161/cbt.5.12.3468
36. Wykosky J, Gibo DM, Debinski W. A novel, potent, and specific ephrinA1-based cytotoxin against EphA2 receptor expressing tumor cells. Mol Cancer Ther 2007; 6:3208-18; PMID:18089715; http://dx.doi.org/10.1158/1535-7163. MCT-07-0200
37. Jackson D, Gooya J, Mao S, Kinneer K, Xu L, Camara M, et al. A human antibody-drug conjugate targeting EphA2 inhibits tumor growth in vivo. Cancer Res 2008; 68:9367-74; PMID:18172292; http://dx.doi.org/10.1158/0008-5472.CAN-08- 1933
38. Pichot CS, Hartig SM, Xia L, Arvanitis C, Monisvais D, Lee FY, et al. Dasatinib synergizes with doxorubicin to block growth, migration, and invasion of breast cancer cells. Br J Cancer 2009; 101:38-47; PMID: 19513066; http://dx.doi.org/10.1038/sj.bjc.6605101
39. Scarberry KE, Mezencev R, McDonald JF. Targeted removal of migratory tumor cells by functionalized magnetic nanoparticles impedes metastasis and tumor progression. Nanomedicine (Lond) 2011; 6:69-78; PMID:21182419; http://dx.doi.org/10.2217/nnm.10.103
40. Kumar SR, Singh J, Xia G, Krasnoperov V, Hassanieh L, Ley EJ, et al. Receptor tyrosine kinase EphB4 is a survival factor in breast cancer. Am J Pathol 2006; 169:279-93; PMID:16816380; http://dx.doi.org/10.2353/ajpath.2006. 050889
41. Noren NK, Yang NY, Silldorff M, Mutyala R, Pasquale EB. Ephrin-independent regulation of cell substrate adhesion by the EphB4 receptor. Biochem J 2009; 422:433-42; PMID:19552627; http://dx.doi.org/10.1042/BJ20090014
42. Rutkowski R, Mertens-Walker I, Lisle JE, Herington AC, Stephenson SA. Evidence for a dual function of EphB4 as tumor promoter and suppressor regulated by the absence or presence of the ephrin-B2 ligand. [E-pub ahead of print]. Int J Cancer 2011. In press. PMID: 22161689
43. Munarini N, Jäger R, Abderhalden S, Zuercher G, Rohrbach V, Loercher S, et al. Altered mammary epithelial development, pattern formation and involution in transgenic mice expressing the EphB4 receptor tyrosine kinase. J Cell Sci 2002; 115:25-37; PMID: 11801721
44. Haldimann M, Custer D, Munarini N, Stirnimann C, Zürcher G, Rohrbach V, et al. Deregulated ephrin-B2 expression in the mammary gland interferes with the development of both the glandular epithelium and vasculature and promotes metastasis formation. Int J Oncol 2009; 35:525-36; PMID:19639173
45. Janes PW, Saha N, Barton WA, Kolev MV, Wimmer-Kleikamp SH, Nievergall E, et al. Adam meets Eph: an ADAM substrate recognition module acts as a molecular switch for ephrin cleavage in trans. Cell 2005; 123:291-304; PMID:16239146; http://dx.doi.org/10.1016/j.cell.2005.08.014
46. Solanas G, Cortina C, Sevillano M, Batlle E. Cleavage of E-cadherin by ADAM10 mediates epithelial cell sorting downstream of EphB signalling. Nat Cell Biol 2011; 13:1100-7; PMID:21804545; http://dx.doi.org/10.1038/ncb2298
47. Miao H, Wang B. Eph/ephrin signaling in epithelial development and homeostasis. Int J Biochem Cell Biol 2009; 41:762-70; PMID:18761422; http://dx.doi.org/10.1016/j.biocel.2008.07.019
48. Zhang J, Hughes S. Role of the ephrin and Eph receptor tyrosine kinase families in angiogenesis and development of the cardiovascular system. J Pathol 2006; 208:453-61; PMID:16470907; http://dx.doi.org/10.1002/path.1937
49. Sawamiphak S, Seidel S, Essmann CL, Wilkinson GA, Pitulescu ME, Acker T, et al. Ephrin-B2 regulates VEGFR2 function in developmental and tumour angiogenesis. Nature 2010; 465:487-91; PMID: 20445540; http://dx.doi.org/10. 1038/nature08995
50. Wang Y, Nakayama M, Pitulescu ME, Schmidt TS, Bochenek ML, Sakakibara A, et al. Ephrin-B2 controls VEGF-induced angiogenesis and lymphangiogenesis. Nature 2010; 465:483-6; PMID:20445537; http://dx.doi.org/10.1038/nature09002
51. Brantley-Sieders DM, Fang WB, Hicks DJ, Zhuang G, Shyr Y, Chen J. Impaired tumor microenvironment in EphA2-deficient mice inhibits tumor angiogenesis and metastatic progression. FASEB J 2005; 19:1884-6; PMID:16166198
52. Brantley-Sieders DM, Fang WB, Hwang Y, Hicks D, Chen J. Ephrin-A1 facilitates mammary tumor metastasis through an angiogenesis-dependent mechanism mediated by EphA receptor and vascular endothelial growth factor in mice. Cancer Res 2006; 66:10315-24; PMID:17079451; http://dx.doi.org/10.1158/0008- 5472.CAN-06-1560
53. Héroult M, Schaffner F, Augustin HG. Eph receptor and ephrin ligand-mediated interactions during angiogenesis and tumor progression. Exp Cell Res 2006; 312:642-50; PMID:16330025; http://dx.doi.org/10.1016/j.yexcr.2005.10. 028
54. Noren NK, Lu M, Freeman AL, Koolpe M, Pasquale EB. Interplay between EphB4 on tumor cells and vascular ephrin-B2 regulates tumor growth. Proc Natl Acad Sci U S A 2004; 101:5583-8; PMID:15067119; http://dx.doi.org/10.1073/pnas. 0401381101
55. Salvucci O, de la Luz Sierra M, Martina JA, McCormick PJ, Tosato G. EphB2 and EphB4 receptors forward signaling promotes SDF-1-induced endothelial cell chemotaxis and branching remodeling. Blood 2006; 108:2914-22; PMID:16840724; http://dx.doi.org/10.1182/blood-2006-05-023341
56. Noberini R, Koolpe M, Peddibhotla S, Dahl R, Su Y, Cosford ND, et al. Small molecules can selectively inhibit ephrin binding to the EphA4 and EphA2 receptors. J Biol Chem 2008; 283:29461-72; PMID:18728010; http://dx.doi.org/10. 1074/jbc.M804103200
57. Foubert P, Silvestre JS, Souttou B, Barateau V, Martin C, Ebrahimian TG, et al. PSGL-1-mediated activation of EphB4 increases the proangiogenic potential of endothelial progenitor cells. J Clin Invest 2007; 117:1527-37; PMID:17510705; http://dx.doi.org/10.1172/JCI28338
58. Andres AC, Djonov V. The mammary gland vasculature revisited. J Mammary Gland Biol Neoplasia 2010; 15:319-28; PMID:20706777; http://dx.doi.org/10.1007/ s10911-010-9186-9
59. Sternlicht MD, Kouros-Mehr H, Lu P, Werb Z. Hormonal and local control of mammary branching morphogenesis. Differentiation 2006; 74:365-81; PMID:16916375; http://dx.doi.org/10.1111/j.1432-0436.2006.00105.x
60. Andres AC, Reid HH, Zürcher G, Blaschke RJ, Albrecht D, Ziemiecki A. Expression of two novel eph-related receptor protein tyrosine kinases in mammary gland development and carcinogenesis. Oncogene 1994; 9:1461-7; PMID:8152808
61. Kouros-Mehr H, Werb Z. Candidate regulators of mammary branching morphogenesis identified by genome-wide transcript analysis. Dev Dyn 2006; 235:3404-12; PMID:17039550; http://dx.doi.org/10.1002/dvdy.20978
62. Vaught D, Chen J, Brantley-Sieders DM. Regulation of mammary gland branching morphogenesis by EphA2 receptor tyrosine kinase. Mol Biol Cell 2009; 20:2572-81; PMID:19321667; http://dx.doi.org/10.1091/mbc.E08-04-0378
63. Fournier MV, Martin KJ, Kenny PA, Xhaja K, Bosch I, Yaswen P, et al. Gene expression signature in organized and growth-arrested mammary acini predicts good outcome in breast cancer. Cancer Res 2006; 66:7095-102; PMID:16849555; http://dx.doi.org/10.1158/0008-5472.CAN-06-0515
64. Nikolova Z, Djonov V, Zuercher G, Andres AC, Ziemiecki A. Cell-type specific and estrogen dependent expression of the receptor tyrosine kinase EphB4 and its ligand ephrin-B2 during mammary gland morphogenesis. J Cell Sci 1998; 111:2741-51; PMID:9718367
65. Weiler S, Rohrbach V, Pulvirenti T, Adams R, Ziemiecki A, Andres AC. Mammary epithelial-specific knockout of the ephrin-B2 gene leads to precocious epithelial cell death at lactation. Dev Growth Differ 2009; 51:809-19; PMID:19843150; http://dx.doi.org/10.1111/j.1440-169X.2009.01140.x
66. Genander M, Frisén J. Ephrins and Eph receptors in stem cells and cancer. Curr Opin Cell Biol 2010; 22:611-6; PMID:20810264; http://dx.doi.org/10. 1016/j.ceb.2010.08.005
67. Nomura T, Göritz C, Catchpole T, Henkemeyer M, Frisén J. EphB signaling controls lineage plasticity of adult neural stem cell niche cells. Cell Stem Cell 2010; 7:730-43; PMID:21112567; http://dx.doi.org/10.1016/j.stem. 2010.11.009
68. Genander M, Halford MM, Xu NJ, Eriksson M, Yu Z, Qiu Z, et al. Dissociation of EphB2 signaling pathways mediating progenitor cell proliferation and tumor suppression. Cell 2009; 139:679-92; PMID:19914164; http://dx.doi.org/10.1016/j.cell.2009.08.048
69. Theus MH, Ricard J, Bethea JR, Liebl DJ. EphB3 limits the expansion of neural progenitor cells in the subventricular zone by regulating p53 during homeostasis and following traumatic brain injury. Stem Cells 2010; 28:1231-42; PMID:20496368
70. Zhou BB, Zhang H, Damelin M, Geles KG, Grindley JC, Dirks PB. Tumor initiating cells: challenges and opportunities for anticancer drug discovery. Nat Rev Drug Disc 2009; 8:806-23; http://dx.doi.org/10.1038/nrd2137
71. Ji H, Goode RJA, Vaillant F, Mathivanan S, Kapp EA, Mathias RA, et al. Proteomic profiling of secretome and adherent plasma membranes from distinct mammary epithelial cell subpopulations. Proteomics 2011; 11:4029-39; PMID:21834135; http://dx.doi.org/10.1002/pmic.201100102
72. Kaenel P, Schwab C, Mülchi K, Wotzkow C, Andres AC. Preponderance of cells with stem cell characteristics in metastasising mouse mammary tumours induced by deregulated EphB4 and ephrin-B2 expression. Int J Oncol 2011; 38:151-60; PMID:21109936
73. Kaenel P, Antonijevic M, Richter S, Küchler S, Sutter N, Wotzkow C, et al. Deregulated ephrin-B2 signaling in mammary epithelial cells alters the stem cell compartment and interferes with the epithelial differentiation pathway. Int J Oncol 2012; 40:357-69; PMID: 22020958
74. Batlle E, Henderson JT, Beghtel H, van den Born MM, Sancho E, Huls G, et al. Beta-catenin and TCF mediate cell positioning in the intestinal epithelium by controlling the expression of EphB/ephrinB. Cell 2002; 111:251-63; PMID:12408869; http://dx.doi.org/10.1016/S0092-8674(02)01015-2
75. Merlos-Suárez A, Batlle E. Eph-ephrin signalling in adult tissues and cancer. Curr Opin Cell Biol 2008; 20:194-200; PMID:18353626; http://dx.doi.org/10.1016/j.ceb.2008.01.011
76. Wang B. Cancer cells exploit the Eph-ephrin system to promote invasion and metastasis: tales of unwitting partners. Sci Signal 2011; 4:pe28; PMID:21632467; http://dx.doi.org/10.1126/scisignal.2002153
77. Astin JW, Batson J, Kadir S, Charlet J, Persad RA, Gillatt D, et al. Competition amongst Eph receptors regulates contact inhibition of locomotion and invasiveness in prostate cancer cells. Nat Cell Biol 2010; 12:1194-204; PMID:21076414; http://dx.doi.org/10.1038/ncb2122
78. Héroult M, Schaffner F, Pfaff D, Prahst C, Kirmse R, Kutschera S, et al. EphB4 promotes site-specific metastatic tumor cell dissemination by interacting with endothelial cell-expressed ephrinB2. Mol Cancer Res 2010; 8:1297-309; PMID:21047731; http://dx.doi.org/10.1158/1541-7786.MCR-09-0453
79. Wang JYJ. Eph tumour suppression: the dark side of Gleevec. Nat Cell Biol 2006; 8:785-6; PMID: 16880809; http://dx.doi.org/10.1038/ncb0806-785