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    Nat Genet. 2007 Nov;39(11):1376-83. Epub 2007 Sep 30.

    EphB-ephrin-B interactions suppress colorectal cancer progression by compartmentalizing tumor cells.

    Cortina C, Palomo-Ponce S, Iglesias M, Fernández-Masip JL, Vivancos A, Whissell G, Humà M, Peiró N, Gallego L, Jonkheer S, Davy A, Lloreta J, Sancho E, Batlle E.

    Oncology Programme, Institute for Research in Biomedicine (IRB), Josep Samitier 1-5, 08028 Barcelona. Spain.

    The genes encoding tyrosine kinase receptors EphB2 and EphB3 are beta-catenin and Tcf4 target genes in colorectal cancer (CRC) and in normal intestinal cells. In the intestinal epithelium, EphB signaling controls the positioning of cell types along the crypt-villus axis. In CRC, EphB activity suppresses tumor progression beyond the earliest stages. Here we show that EphB receptors compartmentalize the expansion of CRC cells through a mechanism dependent on E-cadherin-mediated adhesion. We demonstrate that EphB-mediated compartmentalization restricts the spreading of EphB-expressing tumor cells into ephrin-B1-positive territories in vitro and in vivo. Our results indicate that CRC cells must silence EphB expression to avoid repulsive interactions imposed by normal ephrin-B1-expressing intestinal cells at the onset of tumorigenesis.

    PMID: 17906625 [PubMed - indexed for MEDLINE]

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