Overexpression of Livin promotes migration and invasion of colorectal cancer cells by induction of epithelial–mesenchymal transition via NF-κB activation

Abstract

Livin is a novel member of the inhibitors of apoptosis protein family and has been implicated in the development and progression of colorectal cancer (CRC). However, the underlying mechanisms of Livin in CRC remain not fully understood. In this study, we investigated the effects of Livin expression on the proliferation and metastasis of CRC cells and also addressed its related molecular mechanism to metastasis. The expression of Livin in CRC cells (HCT116, SW480, and HT-29 cell lines) was determined by Western blot analysis. Our results show that the overexpression of Livin significantly promotes the proliferation, migration, and invasion of SW480 cells. Concurrently, the inhibition of Livin reduces the proliferation, migration, and invasion of HCT116 cells. In addition, Livin overexpression promotes the epithelial–mesenchymal transition, as evidenced by a decrease in epithelial E-cadherin expression and an increase in mesenchymal markers, including vimentin, Slug, and Snail. Furthermore, adding the NF-κB inhibitor, BAY 11-7028, or transfecting with small interfering RNA against p65 notably restores the expression level of E-cadherin and attenuates the invasive ability of Livin-overexpressing cells. Taken together, these results indicate that Livin potentiates migration and invasion of CRC cells partially through the induction of epithelial–mesenchymal transition via NF-κB activation. Livin may be a potential therapeutic target for CRC.

Recent developments in targeting genes and pathways by RNAi‐based approaches in colorectal cancer

“…90 Other critical effects of Livin silencing in HCT116 cells was significant reduction in cell proliferation, metastasis, and invasiveness, as well as induction of apoptosis. 88,90 Similar results were observed in Livin shRNA-transfected LoVo cells. 89 The silencing of Livin decreased cell number and proliferation and increased apoptosis and cell sensitivity to Cisplatin, a chemotherapy drug commonly used for cancer treatment, about 50% in these cells.…”

“…In addition, the chemosensitivity of HCT‐8/V to these agents was enhanced 87 . Similarly, the considerable downregulation of Livin mRNA and protein was found in Livin shRNA‐transfected HCT116 cells mediated by Lipofectamine 2000 88 …”

“…The inhibitory effect of Livin knockdown on gene expression was not dose‐dependent and attenuated over time in siRNA transfection HCT116 cells that suggests duration of Livin siRNA is short in these cells, and minimal dosage of siRNA is sufficient for Livin suppression 90 . Other critical effects of Livin silencing in HCT116 cells was significant reduction in cell proliferation, metastasis, and invasiveness, as well as induction of apoptosis 88,90 …”

Copy Number Alterations of Depressed Colorectal Neoplasm Predict the Survival and Response to Oxaliplatin in Proximal Colon Cancer

“…On the basis of the nature of early malignant transformation and aggressively invasive potential in depressed neoplasms, we searched the potential corresponding genes associated with tumorigenesis, invasiveness, or metastasis of CRC by the arm-level change specific to a depressed neoplasm. Among these associated genes, searched by MetaCore Analytical Suite (GeneGo, Saint Joseph, MI, USA) and the GeneCards online database ( ), MYC , CCNA1 , and BIRC7 were identified to be the representatives at chr8, chr13, and chr20, respectively [ 21 , 22 , 23 , 24 ].…”

“…BIRC7 is involved with cell proliferation, invasion, and migration [ 31 ]. Therefore, BIRC7 has be considered to play a critical role in the development of CRC metastasis [ 24 ]. Taken together, MYC might initiate the carcinogenesis of depressed neoplasms at the early stage, and subsequently, CCNA1 and BIRC7 might promote its invasiveness and further migration.…”