title: Role of epithelial to mesenchymal transition in hepatocellular carcinoma.
abstract: The epithelial to mesenchymal transition (EMT) is a multistep biological process whereby epithelial cells change in plasticity by transient de-differentiation into a mesenchymal phenotype. EMT and its reversal, mesenchymal to epithelial transition (MET), essentially occur during embryogenetic morphogenesis and have been increasingly described in fibrosis and cancer during the last decade. In carcinoma progression, EMT plays a crucial role in early steps of metastasis when cells lose cell-cell contacts due to ablation of E-cadherin and acquire increased motility to spread into surrounding or distant tissues. Epithelial plasticity has become a hot issue in hepatocellular carcinoma (HCC), as strong inducers of EMT such as transforming growth factor-β are able to orchestrate both fibrogenesis and carcinogenesis, showing rising cytokine levels in cirrhosis and late stage HCC. In this review, we consider the significance of EMT-MET in malignant hepatocytes as well as changes in the plasticity of hepatic stellate cells for cellular heterogeneity of HCC, and further aim at explaining the current limiting insights into EMT by snapshot analyses of HCC tissues. Recent advances in the identification of clinically relevant mechanisms that impinge on important EMT-transcription factors, as well as on miRNAs causing EMT signatures and HCC progression are highlighted. In addition, we draw particular attention to framing EMT in the context of potential clinical relevance for HCC patients. We conclude that some aspects of EMT are still elusive and further studies are required to better link the clinical management of HCC with biomarkers and targeted therapies related to EMT.
authors.affiliation: Department of Biomedical Sciences and Human Oncology, University of Bari Medical School, Bari, Italy. Electronic address: gianluigi.giannelli@uniba.it.
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Giannelli
authors.affiliation: Department of Medicine I, Division: Institute of Cancer Research, Comprehensive Cancer Center, Medical University of Vienna, Austria.
authors.forename: Petra
authors.initials: P
authors.lastname: Koudelkova
authors.affiliation: Department of Biomedical Sciences and Human Oncology, University of Bari Medical School, Bari, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Dituri
authors.affiliation: Department of Medicine I, Division: Institute of Cancer Research, Comprehensive Cancer Center, Medical University of Vienna, Austria. Electronic address: wolfgang.mikulits@meduniwien.ac.at.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Mikulits
mesh_terms: D015820:Cadherins; D006528:Carcinoma, Hepatocellular; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D008113:Liver Neoplasms; D016212:Transforming Growth Factor beta
chemical_list: D015820:Cadherins; D016212:Transforming Growth Factor beta
keywords: Cell invasion; EMT; Epithelial plasticity; HCC; MET; Patient survival; Therapy; Tumor heterogeneity