Inhibition of PRRX2 suppressed colon cancer liver metastasis via inactivation of Wnt/β-catenin signaling pathway

Abstract

The aim of this study was to investigate whether PRRX2 may regulate the liver metastasis of colon cancer via the Wnt/β-catenin signaling pathway. PRRX2 and β-catenin in patients with the liver metastases of colon cancer was detected by immunochemistry. Colon cancer cells (CT-26 and CMT93) were divided into Normal, si-Ctrl, si-PRRX2 and si-PRRX2 +LiCl groups. Cell invasive and migrating abilities and the related proteins were detected. Liver-metastatic mice model was constructed consisting of Normal, NC shRNA and PRRX2 shRNA groups to examine the function of PRRX2 shRNA on liver metastasis. We found that PRRX2 and β-catenin positive rate was elevated in colon cancer tissues, especially in those tissues with liver metastasis, and there was a close relation between PRRX2 and the clinical staging, lymph node metastasis and numbers of liver metastases of colon cancer patients with liver metastasis. In vitro, the invasive and migrating abilities of CT-26 and CMT93 cells decreased apparently in the si-PRRX2 group, with down-regulation of PRRX2, p-GSK3βSer9/GSK3β, nucleus and cytoplasm β-catenin, TCF4 and Vimentin but up-regulation of E-cadherin. However, LiCl, the Wnt/β-catenin pathway activator, can reverse the inhibitory effect of si-PRRX2 on invasive and migrating ability of colon cancer cells. In vivo, the volume and weight of transplanted tumor and the number of liver metastases in the PRRX2 shRNA group were significantly reduced, with the similar protein expression patterns as in vitro. In a word, PRRX2 inhibition may reduce invasive and migrating abilities to hinder epithelial-mesenchymal transition (EMT), and suppress colon cancer liver metastasis through inactivation of Wnt/β-catenin pathway.