Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenoma / metabolism
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Adenoma / pathology
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Adenoma / prevention & control
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Animals
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Cell Line, Tumor
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Colorectal Neoplasms / metabolism*
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Colorectal Neoplasms / pathology
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Colorectal Neoplasms / prevention & control*
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Disease Progression
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Ephrin-B1 / antagonists & inhibitors
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Ephrin-B1 / genetics
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Ephrin-B1 / metabolism*
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Female
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Gene Expression Regulation, Neoplastic*
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Genes, APC / physiology
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Humans
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Intestinal Mucosa / metabolism
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Intestinal Mucosa / pathology
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Intestinal Neoplasms / metabolism
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Intestinal Neoplasms / pathology
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Intestinal Neoplasms / prevention & control
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Male
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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RNA, Messenger / antagonists & inhibitors
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Receptors, Eph Family / antagonists & inhibitors
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Receptors, Eph Family / genetics
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Receptors, Eph Family / metabolism
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Signal Transduction
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Subcellular Fractions
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TCF Transcription Factors / metabolism
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Transcription Factor 7-Like 2 Protein
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beta Catenin / metabolism
Substances
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Ephrin-B1
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RNA, Messenger
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TCF Transcription Factors
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TCF7L2 protein, human
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Tcf7l2 protein, mouse
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Transcription Factor 7-Like 2 Protein
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beta Catenin
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Receptors, Eph Family