The role of Eph receptors and ephrin ligands in colorectal cancer

International Journal of Cancer

Volumn 126, Issue 9, 2010, Pages 2003-2011

  Herath, Nirmitha I ^a   Boyd, Andrew W ^a,b  

^a ROYAL BRISBANE AND WOMEN'S HOSPITAL   (Australia)

^b UNIVERSITY OF QUEENSLAND   (Australia)

Author keywords

Colon cancer; Colorectal cancer; Eph receptors; Ephrin ligands; Ephs and ephrins

Indexed keywords

EPHRIN; EPHRIN RECEPTOR; LIGAND; PROTEIN TYROSINE KINASE; EPHRIN RECEPTOR A1;

ANGIOGENESIS; BRAIN; CANCER CELL; CANCER GROWTH; CARCINOGENESIS; CELL ADHESION; CELL DIFFERENTIATION; CELL GROWTH; CELL MOTILITY; COLORECTAL CANCER; EMBRYO DEVELOPMENT; GENE EXPRESSION; GENE OVEREXPRESSION; HUMAN; IMMUNOHISTOCHEMISTRY; INTESTINE EPITHELIUM; LIGAND BINDING; LONG TERM POTENTIATION; NONHUMAN; PRIORITY JOURNAL; PROGNOSIS; PROTEIN FUNCTION; PROTEIN LOCALIZATION; PROTEIN PROTEIN INTERACTION; SHORT SURVEY; SIGNAL TRANSDUCTION; TUMOR LOCALIZATION; CELL MOTION; COLORECTAL TUMOR; PHYSIOLOGY; REVIEW;

CELL ADHESION; CELL MOVEMENT; COLORECTAL NEOPLASMS; EPHRINS; HUMANS; LIGANDS; RECEPTOR, EPHA1; SIGNAL TRANSDUCTION;

EID: 77949877661     PISSN: 00207136     EISSN: 10970215     Source Type: Journal    
DOI: 10.1002/ijc.25147     Document Type: Short Survey

References (102)

1. Hunter T. Signaling-2000 and beyond. Cell 2000;100:113-127
2. Blume-Jensen P, Hunter T. Oncogenic kinase signalling. Nature 2001;411: 355-365 (Pubitemid 32467045)
3. 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 (Pubitemid 18046274)
4. Coulthard MG, Lickliter JD, Subanesan N, Chen K, Webb GC, Lowry AJ, Koblar S, Bottema CD, Boyd AW. Characterization of the Epha1 receptor tyrosine kinase: expression in epithelial tissues. Growth Factors 2001;18:303-317 (Pubitemid 32776309)
5. Boyd AW, Ward LD, Wicks IP, Simpson RJ, Salvaris E, Wilks A, Welch K, Loudovaris M, Rockman S, Busmanis I. Isolation and characterization of a novel receptor-type protein tyrosine kinase (hek) from a human pre-B cell line. J Biol Chem 1992;267:3262-3267
6. Cerretti DP, Nelson N. Characterization of the genes for mouse LERK-3/Ephrin-A3 (Epl3), mouse LERK-4/Ephrin-A4 (Epl4), and human LERK-6/Ephrin-A2 (EPLG6): conservation of intron/exon structure. Genomics 1998;47:131-135 (Pubitemid 28080091)
7. Himanen JP, Nikolov DB. Eph signaling: a structural view. Trends Neuorosci 2003; 26:46-51.
8. Lackmann M, Mann RJ, Kravets L, Smith FM, Bucci TA, Maxwell KF, Howlett GJ, Olsson JE, van den Bos T, Cerretti DP, Boyd AW. Ligand for EPH-related kinase (LERK) 7 is the preferred high affinity ligand for the HEK receptor. J Biol Chem 1997;272:16521-16530 (Pubitemid 27276480)
9. Kullander K, Klein R. Mechanisms and functions of Eph and ephrin signalling. Nat Rev Mol Cell Biol 2002;3:475-486 (Pubitemid 34733429)
10. Kalo MS, Pasquale EB. Multiple in vivo tyrosine phosphorylation sites in EphB receptors. Biochemistry 1999;38: 14396-14408
11. Cheng N, Chen J. Tumor necrosis factor-alpha induction of endothelial ephrin A1 expression is mediated by a p38 MAPK-and SAPK/JNK-dependent but nuclear factor-kappa B-independent mechanism. J Biol Chem 2001;276:13771-13777 (Pubitemid 37391752)
12. Parri M, Taddei ML, Bianchini F, Calorini L, Chiarugi P. EphA2 reexpression prompts invasion of melanoma cells shifting from mesenchymal to amoeboid-like motility style. Cancer Res 2009;69:2072-2081
13. Boyd AW, Lackmann M. Signals from Eph and ephrin proteins: a developmental tool kit. Sci STKE 2001;2001:RE20-6.
14. Dodelet VC, Pasquale EB. Eph receptors and ephrin ligands: embryogenesis to tumorigenesis. Oncogene 2000;19:5614-5619
15. Hafner C, Schmitz G, Meyer S, Bataille F, Hau P, Langmann T, Dietmaier W, Landthaler M, Vogt T. Differential gene expression of Eph receptors and Ephrins in benign human tissues and cancers. Clin Chem 2004;50:490-499 (Pubitemid 38297297)
16. Macrae M, Neve RM, Rodriguez-Viciana P, Ha C, Yeh J, Chen C, Gray JW, McCormick F. A conditional feedback loop regulates Ras activity through EphA2. Cancer Cell 2005;8:111-118
17. Wykosky J, Gibo DM, Stanton C, Debinski W. EphA2 as a novel molecular marker and target in glioblastoma multiforme. Mol Cancer Res 2005;3: 541-551
18. Miller MA, Ruest PJ, Kosinski M, Hanks SK, Greenstein D. An Eph receptor sperm-sensing control mechanism for oocyte meiotic maturation in Caenorhabditis elegans. Genes Dev 2003; 17:187-200.
19. Gu C, Shim S, Shin J, Kim J, Park J, Han K, Park S. The EphA8 receptor induces sustained MAP kinase activation to promote neurite outgrowth in neuronal cells. Oncogene 2005;24:4243-4256
20. Furne C, Ricard J, Cabrera JR, Pays L, Bethea JR, Mehlen P, Liebl DJ. EphrinB3 is an anti-apoptotic ligand that inhibits the dependence receptor functions of EphA4 receptors during adult neurogenesis. Biochim Biophys Acta 2009; 1793:231-238
21. Inoue E, Deguchi-Tawarada M, Togawa A, Matsui C, Arita K, Katahira-Tayama S, Sato T, Yamauchi E, Oda Y, Takai Y. Synaptic activity prompts gamma-secretase-mediated cleavage of EphA4 and dendritic spine formation. J Cell Biol 2009;185:551-564
22. Miao H, Li DQ, Mukherjee A, Guo H, Petty A, Cutter J, Basilion JP, Sedor J, Wu J, Danielpour D, Sloan AE, Cohen ML, 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.
23. Noren NK, Yang NY, Silldorff M, Mutyala R, Pasquale EB. Ephrin-independent regulation of cell substrate adhesion by the EphB4 receptor. Biochem J 2009;422:433-442
24. Cowan CA, Henkemeyer M. The SH2/SH3 adaptor Grb4 transduces B-ephrin reverse signals. Nature 2001;413:174-179
25. Bong YS, Lee HS, Carim-Todd L, Mood K, Nishanian TG, Tessarollo L, Daar IO. EphrinB1 signals from the cell surface to the nucleus by recruitment of STAT3. Proc Natl Acad Sci USA 2007;104: 17305-17310
26. Cowan CA, Henkemeyer M. Ephrins in reverse, park and drive. Trends Cell Biol 2002;12:339-346
27. Lu Q, Sun EE, Klein RS, Flanagan JG. Ephrin-B reverse signaling is mediated by a novel PDZ-RGS protein and selectively inhibits G protein-coupled chemoattraction. Cell 2001;105:69-79.
28. Contractor A, Swanson G, Heinemann SF. Kainate receptors are involved in short-and long-term plasticity at mossy fiber synapses in the hippocampus. Neuron 2001;29:209-216
29. Armstrong JN, Saganich MJ, Xu NJ, Henkemeyer M, Heinemann SF, Contractor A. B-ephrin reverse signaling is required for NMDA-independent long-term potentiation of mossy fibers in the hippocampus. J Neurosci 2006;26:3474-3481
30. 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;59:746-758
31. Huynh-Do U, Vindis C, Liu H, Cerretti DP, McGrew JT, Enriquez M, Chen J, Daniel TO. Ephrin-B1 transduces signals to activate integrin-mediated migration, attachment and angiogenesis. J Cell Sci 2002;115:3073-3081
32. Davy A, Robbins SM. Ephrin-A5 modulates cell adhesion and morphology in an integrin-dependent manner. Embo J 2000;19:5396-5405
33. Wilkinson DG. How attraction turns to repulsion. Nat Cell Biol 2003;5:851-853
34. Barrios A, Poole RJ, Durbin L, Brennan C, Holder N, Wilson SW. Eph/Ephrin signaling regulates the mesenchymal-to-epithelial transition of the paraxial mesoderm during somite morphogenesis. Curr Biol 2003;13:1571-1582
35. Henkemeyer M, Orioli D, Henderson JT, Saxton TM, Roder J, Pawson T, Klein R. Nuk controls pathfinding of commissural axons in the mammalian central nervous system. Cell 1996;86:35-46.
36. Orioli D, Henkemeyer M, Lemke G, Klein R, Pawson T. Sek4 and Nuk receptors cooperate in guidance of commissural axons and in palate formation. Embo J 1996;15:6035-6049
37. Noren NK, Pasquale EB. Eph receptor-ephrin bidirectional signals that target Ras and Rho proteins. Cell Signal 2004;16: 655-666
38. Pasquale EB. Eph receptor signalling casts a wide net on cell behaviour. Nat Rev Mol Cell Biol 2005;6:462-475
39. Marston DJ, Dickinson S, Nobes CD. Rac-dependent trans-endocytosis of ephrinBs regulates Eph-ephrin contact repulsion. Nat Cell Biol 2003;5:879-888
40. Zimmer M, Palmer A, Kohler J, Klein R. EphB-ephrinB bi-directional endocytosis terminates adhesion allowing contact mediated repulsion. Nat Cell Biol 2003;5: 869-878
41. Wahl S, Barth H, Ciossek T, Aktories K, Mueller BK. Ephrin-A5 induces collapse of growth cones by activating Rho and Rho kinase. J Cell Biol 2000;149: 263-270
42. Groeger G, Nobes CD. Co-operative Cdc42 and Rho signalling mediates ephrinB-triggered endothelial cell retraction. Biochem J 2007;404:23-29
43. Fang WB, Ireton RC, Zhuang G, Takahashi T, Reynolds A, Chen J. Overexpression of EPHA2 receptor destabilizes adherens junctions via a RhoA-dependent mechanism. J Cell Sci 2008;121:358-368
44. Evans IR, Renne T, Gertler FB, Nobes CD. Ena/VASP proteins mediate repulsion from ephrin ligands. J Cell Sci 2007;120:289-298
45. Pascall JC, Brown KD. Intramembrane cleavage of ephrinB3 by the human rhomboid family protease. RHBDL2. Biochem Biophys Res Commun 2004;317: 244-252
46. Hattori M, Osterfield M, Flanagan JG. Regulated cleavage of a contact-mediated axon repellent. Science 2000;289:1360-1365
47. Janes PW, Saha N, Barton WA, Kolev MV, Wimmer-Kleikamp SH, Nievergall E, Blobel CP, Himanen JP, Lackmann M, Nikolov DB. Adam meets Eph: an ADAM substrate recognition module acts as a molecular switch for ephrin cleavage in trans. Cell 2005;123:291-304.
48. Saito T, Masuda N, Miyazaki T, Kanoh K, Suzuki H, Shimura T, Asao T, Kuwano H. Expression of EphA2 and E-cadherin in colorectal cancer: correlation with cancer metastasis. Oncol Rep 2004;11: 605-611
49. Yuan W, Chen Z, Wu S, Ge J, Chang S, Wang X, Chen J, Chen Z. Expression of EphA2 and E-cadherin in gastric cancer: correlated with tumor progression and lymphogenous metastasis. Pathol Oncol Res, in press.
50. Zantek ND, Azimi M, Fedor-Chaiken M, Wang B, Brackenbury R, Kinch MS. E-cadherin regulates the function of the EphA2 receptor tyrosine kinase. Cell Growth Differ 1999;10:629-638
51. Adams RH. Vascular patterning by Eph receptor tyrosine kinases and ephrins. Semin Cell Dev Biol 2002;13:55-60.
52. Ogawa K, Wada H, Okada N, Harada I, Nakajima T, Pasquale EB, Tsuyama S. EphB2 and ephrin-B1 expressed in the adult kidney regulate the cytoarchitecture of medullary tubule cells through Rho family GTPases. J Cell Sci 2006;119: 559-570
53. Batlle E, Henderson JT, Beghtel H, van den Born MM, Sancho E, Huls G, Meeldijk J, Robertson J, van de Wetering M, Pawson T, Clevers H. Beta-catenin and TCF mediate cell positioning in the intestinal epithelium by controlling the expression of EphB/ephrinB. Cell 2002; 111:251-263
54. Gerlai R. Eph receptors and neural plasticity. Nat Rev Neurosci 2001;2:205-209
55. Brantley-Sieders DM, Chen J. Eph receptor tyrosine kinases in angiogenesis: from development to disease. Angiogenesis 2004;7:17-28. (Pubitemid 39127767)
56. Pandey A, Shao H, Marks RM, Polverini PJ, Dixit VM. Role of B61, the ligand for the Eck receptor tyrosine kinase, in TNF-alpha-induced angiogenesis. Science 1995; 268:567-569
57. Daniel TO, Stein E, Cerretti DP, St John PL, Robert B, Abrahamson DR. ELK and LERK-2 in developing kidney and microvascular endothelial assembly. Kidney Int Suppl 1996;57:S73-81.
58. Ogawa K, Pasqualini R, Lindberg RA, Kain R, Freeman AL, Pasquale EB. The ephrin-A1 ligand and its receptor. Eph. A2, are expressed during tumor neovascularization. Oncogene 2000;19: 6043-6052
59. Brantley-Sieders DM, Caughron J, Hicks D, Pozzi A, Ruiz JC, Chen J. EphA2 receptor tyrosine kinase regulates endothelial cell migration and vascular assembly through phosphoinositide 3-kinase-mediated Rac1 GTPase activation. J Cell Sci 2004;117:2037-2049
60. Wang HU, Chen ZF, Anderson DJ. Molecular distinction and angiogenic interaction between embryonic arteries and veins revealed by ephrin-B2 and its receptor Eph-B4. Cell 1998;93:741-753
61. Adams RH, Wilkinson GA, Weiss C, Diella F, Gale NW, Deutsch U, Risau W, Klein R. Roles of ephrinB ligands and EphB receptors in cardiovascular development: demarcation of arterial/venous domains, vascular morphogenesis, and sprouting angiogenesis. Genes Dev 1999;13:295-306.
62. Gerety SS, Wang HU, Chen ZF, Anderson DJ. Symmetrical mutant phenotypes of the receptor EphB4 and its specific transmembrane ligand ephrin-B2 in cardiovascular development. Mol Cell 1999;4:403-414
63. Adams RH, Klein R. Eph receptors and ephrin ligands. essential mediators of vascular development. Trends Cardiovasc Med 2000;10:183-188
64. Tang XX, Zhao H, Robinson ME, Cohen B, Cnaan A, London W, Cohn SL, Cheung NK, Brodeur GM, Evans AE, Ikegaki N. Implications of EPHB6. EFNB2, and. EFNB3 expressions in human neuroblastoma. Proc Natl Acad Sci USA 2000;97:10936-10941
65. Zelinski DP, Zantek ND, Stewart JC, Irizarry AR, Kinch MS. EphA2 overexpression causes tumorigenesis of mammary epithelial cells. Cancer Res 2001;61:2301-2306
66. 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: 882-892
67. Berclaz G, Flutsch B, Altermatt HJ, Rohrbach V, Djonov V, Ziemiecki A, Dreher E, Andres AC. Loss of EphB4 receptor tyrosine kinase protein expression during carcinogenesis of the human breast. Oncol Rep 2002;9: 985-989
68. Kinch MS, Moore MB, Harpole DH, Jr. Predictive value of the EphA2 receptor tyrosine kinase in lung cancer recurrence and survival. Clin Cancer Res 2003;9: 613-618
69. Nakamura R, Kataoka H, Sato N, Kanamori M, Ihara M, Igarashi H, Ravshanov S, Wang YJ, Li ZY, Shimamura T, Kobayashi T, Konno H, et al. EPHA2/EFNA1 expression in human gastric cancer. Cancer Sci 2005;96: 42-47
70. Kataoka H, Tanaka M, Kanamori M, Yoshii S, Ihara M, Wang YJ, Song JP, Li ZY, Arai H, Otsuki Y, Kobayashi T, Konno H, et al. Expression profile of EFNB1, EFNB2, two ligands of EPHB2 in human gastric cancer. J Cancer Res Clin Oncol 2002;128:343-348
71. 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.
72. Landen CN, Kinch MS, Sood AK. EphA2 as a target for ovarian cancer therapy. Expert Opin Ther Targets 2005;9:1179-1187
73. Sabesan S, Spanevello M, Herath N, Newton T, Duffy S, Lincoln D, Wyld D, Boyle G, Parsons PG, Boyd AW. Over-expression of Eph and ephrin proteins in advanced ovarian epithelial cancer: prognostic variables and potential therapeutic targets. BMC Cancer 2006;6: 144.
74. Batlle E, Bacani J, Begthel H, Jonkheer S, Gregorieff A, van de Born M, Malats N, Sancho E, Boon E, Pawson T, Gallinger S, Pals S, et al. EphB receptor activity suppresses colorectal cancer progression. Nature 2005;435:1126-1130
75. Hafner C, Becker B, Landthaler M, Vogt T. Expression profile of Eph receptors and ephrin ligands in human skin and downregulation of EphA1 in nonmelanoma skin cancer. Mod Pathol 2006;19:1369-1377
76. Brantley DM, Cheng N, Thompson EJ, Lin Q, Brekken RA, Thorpe PE, Muraoka RS, Cerretti DP, Pozzi A, Jackson D, Lin C, Chen J. Soluble Eph A receptors inhibit tumor angiogenesis and progression in vivo. Oncogene 2002;21: 7011-7026
77. Dobrzanski P, Hunter K, Jones-Bolin S, Chang H, Robinson C, Pritchard S, Zhao H, Ruggeri B. Antiangiogenic and antitumor efficacy of EphA2 receptor antagonist. Cancer Res 2004;64:910-919
78. Carles-Kinch K, Kilpatrick KE, Stewart JC, Kinch MS. Antibody targeting of the EphA2 tyrosine kinase inhibits malignant cell behavior. Cancer Res 2002;62: 2840-2847
79. Mao W, Luis E, Ross S, Silva J, Tan C, Crowley C, Chui C, Franz G, Senter P, Koeppen H, Polakis P. EphB2 as a therapeutic antibody drug target for the treatment of colorectal cancer. Cancer Res 2004;64:781-788
80. Kiewlich D, Zhang J, Gross C, Xia W, Larsen B, Cobb RR, Biroc S, Gu JM, Sato T, Light DR, Heitner T, Willuda J, et al. Anti-EphA2 antibodies decrease EphA2 protein levels in murine CT26 colorectal and human MDA-231 breast tumors but do not inhibit tumor growth. Neoplasia 2006;8:18-30.
81. Wykosky J, Gibo DM, Debinski W. A novel, potent, and specific ephrinA1-based cytotoxin against EphA2 receptor expressing tumor cells. Mol Cancer Ther 2007;6:3208-3218
82. Sancho E, Batlle E, Clevers H, Sawai Y, Tamura S, Fukui K, Ito N, Imanaka K, Saeki A, Sakuda S, Kiso S, Matsuzawa Y, et al. Live and let die in the intestinal epithelium. Curr Opin Cell Biol 2003;15: 763-770
83. Kosinski C, Li VS, Chan AS, Zhang J, Ho C, Tsui WY, Chan TL, Mifflin RC, Powell DW, Yuen ST, Leung SY, Chen X. Gene expression patterns of human colon tops and basal crypts and BMP antagonists as intestinal stem cell niche factors. Proc Natl Acad Sci USA 2007;104: 15418-15423
84. Guo DL, Zhang J, Yuen ST, Tsui WY, Chan AS, Ho C, Ji J, Leung SY, Chen X. Reduced expression of EphB2 that parallels invasion and metastasis in colorectal tumours. Carcinogenesis 2006; 27:454-464
85. Jubb AM, Zhong F, Bheddah S, Grabsch HI, Frantz GD, Mueller W, Kavi V, Quirke P, Polakis P, Koeppen H. EphB2 is a prognostic factor in colorectal cancer. Clin Cancer Res 2005;11:5181-5187
86. Lugli A, Spichtin H, Maurer R, Mirlacher M, Kiefer J, Huusko P, Azorsa D, Terracciano L, Sauter G, Kallioniemi OP, Mousses S, Tornillo L. EphB2 expression across 138 human tumor types in a tissue microarray: high levels of expression in gastrointestinal cancers. Clin Cancer Res 2005;11:6450-6458
87. Alazzouzi H, Davalos V, Kokko A, Domingo E, Woerner SM, Wilson AJ, Konrad L, Laiho P, Espin E, Armengol M, Imai K, Yamamoto H, et al. Mechanisms of inactivation of the receptor tyrosine kinase EPHB2 in colorectal tumors. Cancer Res 2005;65:10170-10173
88. Chiu ST, Chang KJ, Ting CH, Shen HC, Li H, Hsieh FJ. Over-expression of EphB3 enhances cell-cell contacts and suppresses tumor growth in HT-29 human colon cancer cells. Carcinogenesis, in press.
89. Liu W, Ahmad SA, Jung YD, Reinmuth N, Fan F, Bucana CD, Ellis LM. Coexpression of ephrin-Bs and their receptors in colon carcinoma. Cancer 2002;94:934-939
90. Stephenson SA, Slomka S, Douglas EL, Hewett PJ, Hardingham JE. Receptor protein tyrosine kinase EphB4 is up-regulated in colon cancer. BMC Mol Biol 2001;2:15.
91. Liu W, Jung YD, Ahmad SA, McCarty MF, Stoeltzing O, Reinmuth N, Fan F, Ellis LM. Effects of overexpression of ephrin-B2 on tumour growth in human colorectal cancer. Br J Cancer 2004;90: 1620-1626
92. Kumar SR, Scehnet JS, Ley EJ, Singh J, Krasnoperov V, Liu R, Manchanda PK, Ladner RD, Hawes D, Weaver FA, Beart RW, Singh G, et al. Preferential induction of EphB4 over EphB2 and its implication in colorectal cancer progression. Cancer Res 2009;69:3736-3745
93. Cortina C, Palomo-Ponce S, Iglesias M, Fernandez-Masip JL, Vivancos A, Whissell G, Huma M, Peiro N, Gallego L, Jonkheer S, Davy A, Lloreta J, et al. EphB-ephrin-B interactions suppress colorectal cancer progression by compartmentalizing tumor cells. Nat Genet 2007;39:1376-1383
94. Maru Y, Hirai H, Takaku F. Overexpression confers an oncogenic potential upon the eph gene. Oncogene 1990;5:445-447
95. Herath NI, Doecke J, Spanevello MD, Leggett BA, Boyd AW. Epigenetic silencing of EphA1 expression in colorectal cancer is correlated with poor survival. Br J Cancer 2009;100:1095-1102
96. 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
97. Kataoka H, Igarashi H, Kanamori M, Ihara M, Wang JD, Wang YJ, Li ZY, Shimamura T, Kobayashi T, Maruyama K, Nakamura T, Arai H, et al. Correlation of EPHA2 overexpression with high microvessel count in human primary colorectal cancer. Cancer Sci 2004;95: 136-141
98. Potla L, Boghaert ER, Armellino D, Frost P, Damle NK. Reduced expression of EphrinA1 (EFNA1) inhibits three-dimensional growth of HT29 colon carcinoma cells. Cancer Lett 2002;175: 187-195
99. Rosenberg IM, Goke M, Kanai M, Reinecker HC, Podolsky DK. Epithelial cell kinase-B61: an autocrine loop modulating intestinal epithelial migration and barrier function. Am J Physiol 1997; 273:G824-32.
100. Sjoblom T, Jones S, Wood LD, Parsons DW, Lin J, Barber TD, Mandelker D, Leary RJ, Ptak J, Silliman N, Szabo S, Buckhaults P, et al. The consensus coding sequences of human breast and colorectal cancers. Science 2006;314:268-274
101. Bardelli A, Parsons DW, Silliman N, Ptak J, Szabo S, Saha S, Markowitz S, Willson JK, Parmigiani G, Kinzler KW, Vogelstein B, Velculescu VE. Mutational analysis of the tyrosine kinome in colorectal cancers. Science 2003;300:949.
102. Wang J, Kataoka H, Suzuki M, Sato N, Nakamura R, Tao H, Maruyama K, Isogaki J, Kanaoka S, Ihara M, Tanaka M, Kanamori M, et al. Downregulation of EphA7 by hypermethylation in colorectal cancer. Oncogene 2005;24:5637-5647