| First Author | Horiguchi H | Year | 2022 |
| Journal | Oncogene | Volume | 41 |
| Issue | 33 | Pages | 4028-4041 |
| PubMed ID | 35831580 | Mgi Jnum | J:327591 |
| Mgi Id | MGI:7333131 | Doi | 10.1038/s41388-022-02405-8 |
| Citation | Horiguchi H, et al. (2022) Tumor cell-derived ANGPTL2 promotes beta-catenin-driven intestinal tumorigenesis. Oncogene 41(33):4028-4041 |
| abstractText | Uncontrolled proliferation of intestinal epithelial cells caused by mutations in genes of the WNT/beta-catenin pathway is associated with development of intestinal cancers. We previously reported that intestinal stromal cell-derived angiopoietin-like protein 2 (ANGPTL2) controls epithelial regeneration and intestinal immune responses. However, the role of tumor cell-derived ANGPTL2 in intestinal tumorigenesis remained unclear. Here, we show that tumor cell-derived ANGPTL2 promotes beta-catenin-driven intestinal tumorigenesis. ANGPTL2 deficiency suppressed intestinal tumor development in an experimental mouse model of sporadic colon cancer. We also found that increased ANGPTL2 expression in colorectal cancer (CRC) cells augments beta-catenin pathway signaling and promotes tumor cell proliferation. Relevant to mechanism, our findings suggest that tumor cell-derived ANGPTL2 upregulates expression of OB-cadherin, which then interacts with beta-catenin, blocking destruction complex-independent proteasomal degradation of beta-catenin proteins. Moreover, our observations support a model whereby ANGPTL2-induced OB-cadherin expression in CRC cells is accompanied by decreased cell surface integrin alpha5beta1 expression. These findings overall provide novel insight into mechanisms of beta-catenin-driven intestinal tumorigenesis. |
