| First Author | Dunkin D | Year | 2018 |
| Journal | Oncotarget | Volume | 9 |
| Issue | 71 | Pages | 33536-33548 |
| PubMed ID | 30323897 | Mgi Jnum | J:298069 |
| Mgi Id | MGI:6457209 | Doi | 10.18632/oncotarget.26086 |
| Citation | Dunkin D, et al. (2018) Intestinal epithelial Notch-1 protects from colorectal mucinous adenocarcinoma. Oncotarget 9(71):33536-33548 |
| abstractText | Increasing evidence links Notch-1 signaling with the maintenance of intestinal architecture and homeostasis. Dysfunction in the common Notch-1 pathway transcription factor recombinant binding protein suppressor of hairless (RBP-J) is associated with loss of epithelial barrier integrity and aberrant conversion of proliferative crypt cells into goblet cells. Furthermore, we have recently discovered that epithelial Notch-1 is indispensable in bridging innate and adaptive immunity in the gut and is required for supporting protective epithelial pro-inflammatory responses. Yet, the epithelial specific function of Notch-1 in intestinal tumorigenesis remains unknown. We generated Villin-Cre/Notch-1 (fl/fl) (VN (-/-) ) mice that are selectively deficient in Notch-1 in intestinal epithelial cells. Intestinal epithelial Notch-1 preserved barrier function and integrity, whereas lack of epithelial Notch-1 induced goblet cell hyperplasia, spontaneous serrated lesions, multifocal low- and high-grade dysplasia and colonic mucinous neoplasms in mice. Over time, VN (-/-) mice displayed high occurrence of colorectal mucinous adenocarcinomas, which correlated with increased levels of mitogenic, angiogenic and pro-tumorigenic gene expression. Finally, we found that the expression of Notch-1 is significantly reduced in human colorectal mucinous adenocarcinoma when compared to colorectal adenocarcinoma. Taken together, our findings reveal a novel and critical protective role for Notch-1 in controlling intestinal tumorigenesis. |
