| First Author | Nakaya T | Year | 2014 |
| Journal | Cancer Res | Volume | 74 |
| Issue | 10 | Pages | 2882-91 |
| PubMed ID | 24626089 | Mgi Jnum | J:211557 |
| Mgi Id | MGI:5575677 | Doi | 10.1158/0008-5472.CAN-13-2574 |
| Citation | Nakaya T, et al. (2014) KLF5 regulates the integrity and oncogenicity of intestinal stem cells. Cancer Res 74(10):2882-91 |
| abstractText | The intestinal epithelium maintains homeostasis by a self-renewal process involving resident stem cells, including Lgr5(+) crypt-base columnar cells, but core mechanisms and their contributions to intestinal cancer are not fully defined. In this study, we examined a hypothesized role for KLF5, a zinc-finger transcription factor that is critical to maintain the integrity of embryonic and induced pluripotent stem cells, in intestinal stem-cell integrity and cancer in the mouse. Klf5 was indispensable for the integrity and oncogenic transformation of intestinal stem cells. In mice, inducible deletion of Klf5 in Lgr5(+) stem cells suppressed their proliferation and survival in a manner associated with nuclear localization of beta-catenin (Catnb), generating abnormal apoptotic cells in intestinal crypts. Moreover, production of lethal adenomas and carcinomas by specific expression of an oncogenic mutant of beta-catenin in Lgr5(+) stem cells was suppressed completely by Klf5 deletion in the same cells. Given that activation of the Wnt/beta-catenin pathway is the most frequently altered pathway in human colorectal cancer, our results argue that KLF5 acts as a fundamental core regulator of intestinal oncogenesis at the stem-cell level, and they suggest KLF5 targeting as a rational strategy to eradicate stem-like cells in colorectal cancer. |
