| First Author | Bennecke M | Year | 2010 |
| Journal | Cancer Cell | Volume | 18 |
| Issue | 2 | Pages | 135-46 |
| PubMed ID | 20708155 | Mgi Jnum | J:163673 |
| Mgi Id | MGI:4829416 | Doi | 10.1016/j.ccr.2010.06.013 |
| Citation | Bennecke M, et al. (2010) Ink4a/Arf and oncogene-induced senescence prevent tumor progression during alternative colorectal tumorigenesis. Cancer Cell 18(2):135-46 |
| abstractText | Colonic cancers with a serrated morphology have been proposed to comprise a molecularly distinct tumor entity following an alternative pathway of genetic alterations independently of APC mutations. We demonstrate that intestinal epithelial cell specific expression of oncogenic K-ras(G12D) in mice induces serrated hyperplasia, which is characterized by p16(ink4a) overexpression and induction of senescence. Deletion of Ink4a/Arf in K-ras(G12D) expressing mice prevents senescence and leads to invasive, metastasizing carcinomas with morphological and molecular alterations comparable to human KRAS mutated serrated tumors. Thus, we suggest that oncogenic K-ras represents a key player during an alternative, serrated pathway to colorectal cancer and hence propose RAS-RAF-MEK signaling apart from APC as an additional gatekeeper in colorectal tumor development. |
