| First Author | Lu T | Year | 2017 |
| Journal | Oncotarget | Volume | 8 |
| Issue | 12 | Pages | 18979-18990 |
| PubMed ID | 28145888 | Mgi Jnum | J:258487 |
| Mgi Id | MGI:6147915 | Doi | 10.18632/oncotarget.14866 |
| Citation | Lu T, et al. (2017) Adamts18 deficiency promotes colon carcinogenesis by enhancing beta-catenin and p38MAPK/ERK1/2 signaling in the mouse model of AOM/DSS-induced colitis-associated colorectal cancer. Oncotarget 8(12):18979-18990 |
| abstractText | ADAMTS18 is a novel tumor suppressor and is critical to the pathology of human colorectal cancer. However, the underlying mechanism is not clear. Here we generated an Adamts18-deficient mouse strain as an in vivo model to investigate the role of ADAMTS18 in the pathogenesis of colorectal cancer. In AOM/DSS-induced colitis-associated colorectal cancer, the deficiency of Adamts18 in mice resulted in enhanced tumorigenesis and colon inflammation that could be attributed in part to enhanced nuclear translocation of beta-catenin and elevated expression of its downstream target genes, cyclin D1 and c-myc. Moreover, increased p38MAPK and ERK1/2 activities were detected in colon cancer cells from Adamts18-deficient mice. Further studies revealed that ADAMTS18 deficiency reduced intestinal E-cadherin levels in mice, which ultimately led to intestinal barrier dysfunction. These data indicate that Adamts18 deficiency enhances tumorigenesis and intestinal inflammation through elevated Wnt/beta-catenin and p38MAPK/ERK1/2 signaling and promotes colon cancer in this mouse model. |
