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

作者：Kundu Parag; Genander Maria; Straat Klas; Classon Johanna; Ridgway Rachel A; Tan Ee Hong; Bjork Jan; Martling Anna; van Es Johan; Sansom Owen J; Clevers Hans; Pettersson Sven^*; Frisen Jonas

来源：Science Translational Medicine, 2015, 7(281): 281ra44.

DOI：10.1126/scitranslmed.3010567

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.

• 出版日期2015-4-1
• 单位南阳理工学院