Inflammation-driven colon neoplasmatogenesis in uPA-deficient mice is associated with an increased expression of Runx transcriptional regulators
| Autor: | George S. Karagiannis, Katerina Angelopoulou, Theofilos Poutahidis, Hara Afaloniati, Alexandros Hardas |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Cell type Transcription Genetic Core Binding Factor Alpha 1 Subunit Smad Proteins SMAD Biology medicine.disease_cause Bone morphogenetic protein 03 medical and health sciences Mice 0302 clinical medicine Claudin-1 medicine Animals Humans Transcription factor Mice Knockout Bcl-2-Like Protein 11 Dextran Sulfate Cell Biology Colitis Urokinase-Type Plasminogen Activator RUNX2 Gene Expression Regulation Neoplastic SNAI2 Disease Models Animal 030104 developmental biology Core Binding Factor Alpha 3 Subunit 030220 oncology & carcinogenesis Bone Morphogenetic Proteins Core Binding Factor Alpha 2 Subunit Cancer research Snail Family Transcription Factors Signal transduction Carcinogenesis Colorectal Neoplasms Signal Transduction |
| Zdroj: | Experimental cell research. 361(2) |
| ISSN: | 1090-2422 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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