1. Inhibition of PRRX2 suppressed colon cancer liver metastasis via inactivation of Wnt/β-catenin signaling pathway
- Author
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Ning-Gang Zheng, Wen-Xiao Chai, Li-Guo Sun, Hong-Yi Cai, Fu-Hong Dai, and Hong-Sheng Shao
- Subjects
Male ,0301 basic medicine ,Epithelial-Mesenchymal Transition ,Colorectal cancer ,Cell ,Vimentin ,Pathology and Forensic Medicine ,Metastasis ,Small hairpin RNA ,03 medical and health sciences ,0302 clinical medicine ,Cell Movement ,In vivo ,medicine ,Humans ,RNA, Small Interfering ,Wnt Signaling Pathway ,beta Catenin ,Aged ,Homeodomain Proteins ,biology ,business.industry ,Liver Neoplasms ,Wnt signaling pathway ,Cell Biology ,Middle Aged ,Cadherins ,medicine.disease ,Gene Expression Regulation, Neoplastic ,030104 developmental biology ,medicine.anatomical_structure ,Lymphatic Metastasis ,030220 oncology & carcinogenesis ,Colonic Neoplasms ,Cancer research ,biology.protein ,Female ,Signal transduction ,business - 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.
- Published
- 2019