Adamts18 deficiency promotes colon carcinogenesis by enhancing β-catenin and p38MAPK/ERK1/2 signaling in the mouse model of AOM/DSS-induced colitis-associated colorectal cancer

作者：Lu, Tiantian; Dang, Suying^*; Zhu, Rui; Wang, Ying; Nie, Zongying; Hong, Tao; Zhang, Wei^*

来源：Oncotarget, 2017, 8(12): 18979-18990.

DOI：10.18632/oncotarget.14866

• ADAMTS18
• colitis-associated colorectal cancer
• inflammation
• tumorigenesis

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 colitisassociated 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.

• 出版日期2017-3-21
• 单位上海交通大学; 上海南方模式生物研究中心; 华东师范大学