Letter abstract
Nature Genetics 39, 1376 - 1383 (2007)
Published online: 30 September 2007 | doi:10.1038/ng.2007.11
EphB–ephrin-B interactions suppress colorectal cancer progression by compartmentalizing tumor cells
Carme Cortina1,5, Sergio Palomo-Ponce1,5, Mar Iglesias2, Juan Luis Fernández-Masip1, Ana Vivancos1, Gavin Whissell1, Mireia Humà1, Nerea Peiró1, Lourdes Gallego1, Suzanne Jonkheer1, Alice Davy3, Josep Lloreta2, Elena Sancho1 & Eduard Batlle1,4
The genes encoding tyrosine kinase receptors EphB2 and EphB3 are 
-catenin and Tcf4 target genes in colorectal cancer (CRC) and in normal intestinal cells1, 2. In the intestinal epithelium, EphB signaling controls the positioning of cell types along the crypt-villus axis1. In CRC, EphB activity suppresses tumor progression beyond the earliest stages3, 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.
- Oncology Programme, Institute for Research in Biomedicine (IRB), Josep Samitier 1-5, 08028 Barcelona. Spain.
- Department of Pathology, Hospital Universitari del Mar, Universitat Autònoma de Barcelona, Barcelona, Spain.
- Centre de Biologie du Developpement, CNRS/UPS, 118 Route de Narbonne, Bat 4R3, 31062 Toulouse cedex 4, France.
- Institució Catalana de Recerca i Estudis Avançats (ICREA).
- These authors contributed equally to this work.
Correspondence to: Eduard Batlle1,4 e-mail: eduard.batlle@irbbarcelona.org
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