An EphB-Abl signaling pathway is associated with intestinal tumor initiation and growth

Parag Kundu, Maria Genander, Klas Strååt, Johanna Classon, Rachel A Ridgway, Ee Hong Tan, Jan Björk, Anna Martling, Johan van Es, Owen J Sansom, Hans Clevers, Sven Pettersson, Jonas Frisén

Onderzoeksoutput: Bijdrage aan wetenschappelijk tijdschrift/periodieke uitgaveArtikelWetenschappelijkpeer review


EphB receptors regulate the proliferation and positioning of intestinal stem and progenitor cells. In addition, they can act as tumor promoters for adenoma development but suppress progression to invasive carcinoma. We used imatinib to abrogate Abl kinase activity in Apc(Min/+) mice and in mice with LGR5(+) stem cells that were genetically engineered to develop adenomatous polyposis coli. Imatinib treatment inhibited the tumor-promoting effects of EphB signaling without attenuating EphB-mediated tumor suppression, demonstrating a role for EphB signaling in the initiation of intestinal tumors. The imatinib treatment regimen extended the life span of Apc(Min/+) mice and reduced cell proliferation in cultured slices of adenomas from patients with familial adenomatous polyposis. These findings connect the EphB signaling pathway to the regulation of intestinal adenoma initiation via Abl kinase. Our findings may have clinical implications for pharmacological therapy against adenoma formation and cancer progression in patients predisposed to develop colorectal cancer.

Originele taal-2Engels
Pagina's (van-tot)281ra44
TijdschriftScience Translational Medicine
Nummer van het tijdschrift281
StatusGepubliceerd - 01 apr. 2015


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