Journal
NATURE GENETICS
Volume 39, Issue 11, Pages 1376-1383Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ng.2007.11
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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(1,2). In the intestinal epithelium, EphB signaling controls the positioning of cell types along the crypt-villus axis(1). In CRC, EphB activity suppresses tumor progression beyond the earliest stages(3,4). 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.
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