Network analysis and proteomic identification of vimentin as a key regulator associated with invasion and metastasis in human hepatocellular carcinoma cells

Poor prognoses have long been associated with the high relapse and metastasis of human hepatocellular carcinoma (HCC). To achieve long-term survival, it is necessary to identify new HCC biomarkers and investigate their roles in cell mobility and invasiveness. Of note, overexpression of vimentin (Vim) was significantly correlated with tumor nuclear grade (p=0.01) and the invasive potential, indicating that Vim may be a promising candidate in regulating HCC metastasis. RNA interference-mediated silencing of Vim (siVim) suppressed the invasive and migratory propensity, and matrix metalloproteinase (MMP)-9 activity, and elicited morphological changes in poorly differentiated SK-Hep-1 cells. Moreover, we performed a comprehensive proteomic analysis to survey global protein changes mediated by siVim in SK-Hep-1 cells. Significant changes in cytoskeleton protein but not messenger RNA levels encoding these targeted proteins were observed. All of the data in the current study and a network analysis implied that abolition of Vim may disturb the expression and stability of various cytoskeletal proteins through promoting the ubiquitin system, resulting in impaired cell adhesion and motility. Collectively, an integrated approach represents a modality to explore novel relationships in a proteome complex and highlights the functional roles of Vim in HCC metastasis. This article is part of a Special Issue entitled: Translational Proteomics. (C) 2012 Elsevier B.V. All rights reserved.