Inflammation-driven colon neoplasmatogenesis in uPA-deficient mice is associated with an increased expression of Runx transcriptional regulators

Hara Afaloniati, George S. Karagiannis, Alexandros Hardas, Theofilos Poutahidis, Katerina Angelopoulou

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)257-264
Number of pages8
JournalExperimental Cell Research
Volume361
Issue number2
DOIs
StatePublished - Dec 15 2017

Keywords

  • Bone morphogenetic proteins (BMP)
  • Colorectal cancer (CRC)
  • Dextran sodium sulfate (DSS)
  • Mouse model
  • Runx
  • Smad

ASJC Scopus subject areas

  • Cell Biology

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