Effect of IMP3 on epithelial-to-mesenchymal transition and the function of colon cancer stem cells.

Abstract

631 Background: EMT could promote the acquisition of stem-like properties in cancer cells and cancer stem cell (CSC) has EMT properties. However, the underlying mechanism of the interaction between EMT and CSC still remain unclear. We previously identified Insulin-like growth factor-II mRNA-binding protein 3 (IMP3) plays a vital role in colon cancer carcinogenesis. Here, we aimed to identify the gene function between EMT and CSC in colon cancer. Methods: The expression of IMP3 was analyzed in human tumor tissues. Colonospheres were isolated from colon cancer cell lines and the biological features of IMP3 were investigated in the process of EMT and colonoshpere cells. Results: Increased IMP3 levels were significantly correlated with higher clinical stage, T classification, LNM, presence of distant metastasis. Patients with IMP3-positive localized tumors had lower 5-year disease-free survival (DFS) and overall survival (OS) than those with IMP3-negative tumors. Multivariate survival analysis showed that IMP3 was an independent prognostic marker for DFS and OS. Expanded colonospheres contained cells that expressed high levels of CD133 and had the ability to promote migration and activate the epithelial-mesenchymal transition. Down regulation of IMP3 in HCT116 cells inhibited the invasion, migration ability and epithelial-mesenchymal transition and the properties of colonospheres. Conclusions: These findings suggest that IMP3 plays an important role in colon cancer tumorigenesis and metastasis through transactivation of colon CSC with EMT property, which is helpful to identify critical marker and therapeutic target.