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Barker N, van Es JH, Kuipers J, Kujala P, van den Born M, Cozijnsen M, Haegebarth A, Korving J, Begthel H, Peters PJ, et al.: Identification of stem cells in small intestine and colon by marker gene Lgr5. Nature 2007, 449:1003-10U1. Identification of ISCs in the crypts by genetic analysis. This paper shows for the first time that ISCs reside at the crypt base intermingled with PCs, instead of at +4 position as previously thought.
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The beta-catenin/TCF-4 complex imposes a crypt progenitor phenotype on colorectal cancer cells
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van de Wetering M., Sancho E., Verweij C., de Lau W., Oving I., Hurlstone A., van der H.K., Batlle E., Coudreuse D., Haramis A.P., et al. The beta-catenin/TCF-4 complex imposes a crypt progenitor phenotype on colorectal cancer cells. Cell 111 (2002) 241-250
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van Es J.H., Jay P., Gregorieff A., van Gijn M.E., Jonkheer S., Hatzis P., Thiele A., van den Born M., Begthel H., Brabletz T., et al. Wnt signalling induces maturation of Paneth cells in intestinal crypts. Nat Cell Biol 7 (2005) 381-437
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Clevers H., and Batlle E. EphB/EphrinB receptors and Wnt signaling in colorectal cancer. Cancer Res 66 (2006) 2-5
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Gregorieff A., and Clevers H. Wnt signaling in the intestinal epithelium: from endoderm to cancer. Genes Dev 19 (2005) 877-890
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Beta-catenin and TCF mediate cell positioning in the intestinal epithelium by controlling the expression of EphB/ephrinB
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First description of intestinal phenotypes in EphB2 and EphB3 mutant mice. The observations described here imply that not all the instructions codified by beta-catenin/Tcf genetic programme regulate cell growth. Apparently, Wnt signalling also controls cell positioning in the crypts by regulating the expression domains of EphB receptors and ephrinB ligands.
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Batlle E., Henderson J.T., Beghtel H., van den Born M.M., Sancho E., Huls G., Meeldijk J., Robertson J., van de W.M., Pawson T., et al. Beta-catenin and TCF mediate cell positioning in the intestinal epithelium by controlling the expression of EphB/ephrinB. Cell 111 (2002) 251-263. First description of intestinal phenotypes in EphB2 and EphB3 mutant mice. The observations described here imply that not all the instructions codified by beta-catenin/Tcf genetic programme regulate cell growth. Apparently, Wnt signalling also controls cell positioning in the crypts by regulating the expression domains of EphB receptors and ephrinB ligands.
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Batlle, E.1
Henderson, J.T.2
Beghtel, H.3
van den Born, M.M.4
Sancho, E.5
Huls, G.6
Meeldijk, J.7
Robertson, J.8
van de, W.M.9
Pawson, T.10
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12
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35548976379
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EphB-ephrinB interactions suppress colorectal cancer progression by compartmentalizing tumor cells
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This paper shows that tumor cells that express EphB receptors cannot colonize ephrinB1 positive areas of the intestine. This phenomenon is described as tumor compartmentalization and results in tumor suppression in the colon. The mechanism depends on the ability of EphB signalling to enforce E-cadherin adhesion.
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Cortina C., Palomo-Ponce S., Iglesias M., Fernandez-Masip J.L., Vivancos A., Whissell G., Huma M., Peiro N., Gallego L., Jonkheer S., et al. EphB-ephrinB interactions suppress colorectal cancer progression by compartmentalizing tumor cells. Nat Genet 39 (2007) 1376-1383. This paper shows that tumor cells that express EphB receptors cannot colonize ephrinB1 positive areas of the intestine. This phenomenon is described as tumor compartmentalization and results in tumor suppression in the colon. The mechanism depends on the ability of EphB signalling to enforce E-cadherin adhesion.
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Nat Genet
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Cortina, C.1
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Gallego, L.9
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33744980881
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EphB receptors coordinate migration and proliferation in the intestinal stem cell niche
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Describes defects in cell proliferation in the intestine of EphB2/-B3 mutant mice which apparently are not linked to cell positioning alterations. This article suggests a role for EphB signalling in inducing cell proliferation. It would be interesting to reinterpret these observations in light of the identification of ISCs in the crypt base and of the re-distribution of cell types present in EphB mutant mice.
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Holmberg J., Genander M., Halford M.M., Anneren C., Sondell M., Chumley M.J., Silvany R.E., Henkemeyer M., and Frisen J. EphB receptors coordinate migration and proliferation in the intestinal stem cell niche. Cell 125 (2006) 1151-1163. Describes defects in cell proliferation in the intestine of EphB2/-B3 mutant mice which apparently are not linked to cell positioning alterations. This article suggests a role for EphB signalling in inducing cell proliferation. It would be interesting to reinterpret these observations in light of the identification of ISCs in the crypt base and of the re-distribution of cell types present in EphB mutant mice.
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Cell
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Holmberg, J.1
Genander, M.2
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Chumley, M.J.6
Silvany, R.E.7
Henkemeyer, M.8
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Andres A.C., and Ziemiecki A. Eph and ephrin signaling in mammary gland morphogenesis and cancer. J Mammary Gland Biol 8 (2003) 475-485
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Andres, A.C.1
Ziemiecki, A.2
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Munarini N., Jager R., Abderhalden S., Zuercher G., Rohrbach V., Loercher S., Pfanner-Meyer B., Andres A.C., and Ziemiecki A. Altered mammary epithelial development, pattern formation and involution in transgenic mice expressing the EphB4 receptor tyrosine kinase. J Cell Sci 115 (2002) 25-37
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Munarini, N.1
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Pfanner-Meyer, B.7
Andres, A.C.8
Ziemiecki, A.9
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EphB2 and ephrin-B1 expressed in the adult kidney regulate the cytoarchitecture of medullary tubule cells through Rho family GTPases
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Ogawa K., Wada H., Okada N., Harada I., Nakajima T., Pasquale E.B., and 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 119 (2006) 559-570
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Tsuyama, S.7
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17
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Eph kinases and ephrins support thrombus growth and stability by regulating integrin outside-in signaling in platelets
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Describes the requirement of Eph-ephrin signalling for the proper growth and stability of platelet aggregates in thrombus.
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Prevost N., Woulfe D.S., Jiang H., Stalker T.J., Marchese P., Ruggeri Z.M., and Brass L.F. Eph kinases and ephrins support thrombus growth and stability by regulating integrin outside-in signaling in platelets. Proc Natl Acad Sci U S A 102 (2005) 9820-9825. Describes the requirement of Eph-ephrin signalling for the proper growth and stability of platelet aggregates in thrombus.
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Proc Natl Acad Sci U S A
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Prevost, N.1
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Marchese, P.5
Ruggeri, Z.M.6
Brass, L.F.7
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18
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EphB6-null mutation results in compromised T cell function
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Luo H.Y., Yu G., Tremblay J., and Wu J.P. EphB6-null mutation results in compromised T cell function. J Clin Invest 114 (2004) 1762-1773
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Yu G., Mao J.N., Wu Y.L., Luo H.Y., and Wu J.P. Ephrin-B1 is critical in T-cell development. J Biol Chem 281 (2006) 10222-10229
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Yu G., Luo H.Y., Wu Y.L., and Wu J.P. Ephrin B2 induces T cell costimulation. J Immunol 171 (2003) 106-114
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EphA-ephrinA-mediated beta cell communication regulates insulin secretion from pancreatic islets
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This is the only report to date describing a role for Ephs and ephrins in the pancreas. It shows in vivo requirement of Eph-ephrin signalling in an exocytotic event. This observation may have therapeutic implications for treatment of diabetes.
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Konstantinova I., Nikolova G., Ohara-Imaizumi M., Meda P., Kucera T., Zarbalis K., Wurst W., Nagamatsu S., and Lammert E. EphA-ephrinA-mediated beta cell communication regulates insulin secretion from pancreatic islets. Cell 129 (2007) 359-370. This is the only report to date describing a role for Ephs and ephrins in the pancreas. It shows in vivo requirement of Eph-ephrin signalling in an exocytotic event. This observation may have therapeutic implications for treatment of diabetes.
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Cell
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Konstantinova, I.1
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A systematic description and analysis of beta-catenin/Tcf target genes in intestinal crypts.
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First description of EphB2, EphB3 and EphB4 silencing in CRC and in vivo demonstration using animal models of CRC that blockage of EphB activity plays an important role in the adenoma-carcinoma transition.
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Batlle E., Bacani J., Begthel H., Jonkeer S., Gregorieff A., van de Born M., Malats N., Sancho E., Boon E., Pawson T., et al. EphB receptor activity suppresses colorectal cancer progression. Nature 435 (2005) 1126-1130. First description of EphB2, EphB3 and EphB4 silencing in CRC and in vivo demonstration using animal models of CRC that blockage of EphB activity plays an important role in the adenoma-carcinoma transition.
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Batlle, E.1
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Jubb A.M., Zhong F., Bheddah S., Grabsch H.I., Frantz G.D., Mueller W., Kavi V., Quirke P., Polakis P., and Koeppen H. EphB2 is a prognostic factor in colorectal cancer. Clin Cancer Res 11 (2005) 5181-5187
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Kaidi A., Moorghen M., Williams A.C., and Paraskeva C. Is the downregulation of EphB2 receptor expression during colorectal tumorigenesis due to hypoxia?. Gut 56 (2007) 1637-1638
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Huusko P., Ponciano-Jackson D., Wolf M., Kiefer J.A., Azorsa D.O., Tuzmen S., Weaver D., Robbins C., Moses T., Allinen M., et al. Nonsense-mediated decay microarray analysis identifies mutations of EPHB2 in human prostate cancer. Nat Genet 36 (2004) 979-983
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Kittles R.A., Baffoe-Bonnie A.B., Moses T.Y., Robbins C.M., Ahaghotu C., Huusko P., Pettaway C., Vijayakumar S., Bennett J., Hoke G., et al. A common nonsense mutation in EphB2 is associated with prostate cancer risk in African American men with a positive family history. J Med Genet 43 (2006) 507-511
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The receptor tyrosine kinase EphA2 promotes mammary adenocarcinoma tumorigenesis and metastatic progression in mice by amplifying ErbB2 signaling
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ErbB2-induced tumorigenesis is enhanced in the presence of EphA2. The authors show that ErbB2 and EphA2 interact and activate Ras-MAPK and Rho GTPases, thus promoting tumor cell proliferation and motility. This work enhances the notion that Eph oncogenic potential depends on the cellular context.
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Brantley-Sieders D.M., Zhuang G.L., Hicks D.J., Fang W.B., Hwang Y., Cates J.M.M., Coffman K., Jackson D., Bruckheimer E., Muraoka-Cook R.S., et al. The receptor tyrosine kinase EphA2 promotes mammary adenocarcinoma tumorigenesis and metastatic progression in mice by amplifying ErbB2 signaling. J Clin Invest (2007). ErbB2-induced tumorigenesis is enhanced in the presence of EphA2. The authors show that ErbB2 and EphA2 interact and activate Ras-MAPK and Rho GTPases, thus promoting tumor cell proliferation and motility. This work enhances the notion that Eph oncogenic potential depends on the cellular context.
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J Clin Invest
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Brantley-Sieders, D.M.1
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EphA2 receptor tyrosine kinase as a promising target for cancer therapeutics
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Ireton, R.C.1
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The EphB4 receptor suppresses breast cancer cell tumorigenicity through an Abl-Crk pathway
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This work reveals a tumor suppressor role for EphB4 receptor in breast cancer and identifies the Abl-Crk pathway as the main effector of EphB4-induced inhibition of proliferation and cell migration.
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Noren N.K., Foos G., Hauser C.A., and Pasquale E.B. The EphB4 receptor suppresses breast cancer cell tumorigenicity through an Abl-Crk pathway. Nat Cell Biol 8 (2006) 815-825. This work reveals a tumor suppressor role for EphB4 receptor in breast cancer and identifies the Abl-Crk pathway as the main effector of EphB4-induced inhibition of proliferation and cell migration.
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