| First Author | Afaloniati H | Year | 2017 |
| Journal | Exp Cell Res | Volume | 361 |
| Issue | 2 | Pages | 257-264 |
| PubMed ID | 29107070 | Mgi Jnum | J:260887 |
| Mgi Id | MGI:6151949 | Doi | 10.1016/j.yexcr.2017.10.025 |
| Citation | Afaloniati H, et al. (2017) Inflammation-driven colon neoplasmatogenesis in uPA-deficient mice is associated with an increased expression of Runx transcriptional regulators. Exp Cell Res 361(2):257-264 |
| abstractText | Deregulation of the bone morphogenetic protein (BMP) pathway has been documented in colorectal cancer (CRC). Previously, we investigated possible associations between urokinase-type plasminogen activator (uPA) deficiency and expression of extracellular constituents of BMP signaling in a newly developed mouse model of inflammation-driven intestinal neoplasmatogenesis, in which chronic colitis and CRC are induced using dextran sodium sulfate (DSS). In this report, we explored the contribution of intracellular components of Smad-mediated BMP signal transduction using the same model. Interestingly, upon DSS treatment, we noticed an overexpression of Runx1/2/3 transcription factors in both wild-type and uPA-deficient mice. Moreover, Runx1 and Runx2 expression levels exhibited an even higher increase in DSS-treated/uPA-deficient mice as compared to DSS-treated/wild-type animals. In all experimental conditions, in situ investigation of Runx-expressing cell types, revealed detection of all three Runx in the immune cells, yet in the DSS-treated/uPA-deficient mice Runx1 and Runx2 were also identified in the preneoplastic epithelium of advanced high-grade dysplasia and carcinoma in-situ colonic lesions. Finally, the uPA-deficient pro-tumorigenic colitic microenvironment exhibited increased levels of the Runx-induced target genes Snai2, Bim and Claudin1, known to have a role in tumor development and progression. These findings suggest that the absence of uPA correlates with increased levels of Runx transcriptional regulators in a way that promotes inflammation-associated carcinogenesis. |
