SerpinB3 upregulates the Cyclooxygenase-2 / β-Catenin positive loop in colorectal cancer

Abstract

Colorectal cancer is characterized by aberrant Cyclooxigenase-2 (COX-2) and β-Catenin pathways. Recently, the protease inhibitor SerpinB3 has been described overexpressed in more advanced stages of this tumor. Aim of the study was to explore the possible relationship between these molecules in this setting. We evaluated colorectal cancer specimens from 105 patients and a positive correlation between SerpinB3, COX-2 and β-Catenin expression was observed, with higher levels in tumor than in adjacent tissue. The highest levels were associated with pathologic parameters of poor prognosis, including vascular invasion, lymph node metastasis and perineural invasion. The molecular and protein profiles of COX-2 and β-Catenin were analyzed in cell lines with different expression of SerpinB3. In those with high expression of SerpinB3, COX-2 and β-Catenin were higher than in controls. Cells with high levels of SerpinB3 showed higher proliferation and invasion compared to controls. In conclusion, in colorectal cancer SerpinB3, COX-2 and β-Catenin are positively correlated and associated with more advanced tumor stage. The in vitro experimental results support a driving role of SerpinB3 in the upregulation of COX-2/ β-Catenin positive loop, associated with a more aggressive cellular phenotype.