Abstract:
: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.
journal_name
Sci Transl Medjournal_title
Science translational medicineauthors
Kundu P,Genander M,Strååt K,Classon J,Ridgway RA,Tan EH,Björk J,Martling A,van Es J,Sansom OJ,Clevers H,Pettersson S,Frisén Jdoi
10.1126/scitranslmed.3010567subject
Has Abstractpub_date
2015-04-01 00:00:00pages
281ra44issue
281eissn
1946-6234issn
1946-6242pii
7/281/281ra44journal_volume
7pub_type
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