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.

The Expression and Functional Significance of Runx2 in Hepatocellular Carcinoma: Its Role in Vasculogenic Mimicry and Epithelial–Mesenchymal Transition

“…The growth and metastasis of a tumor depends on its own vascular network. Apart from the vessel tunnels, which are lined with endothelial cells, Maniotis et al found a new microcirculation mechanism: channels are externally lined with tumor cells, with no endothelial cells in human melanoma [5]. This phenomenon has been termed vasculogenic mimicry (VM).…”

Long Non-Coding RNA ZEB1-Antisense 1 Affects Cell Migration and Invasion of Cervical Cancer by Regulating Epithelial-Mesenchymal Transition via the p38MAPK Signaling Pathway

“…Besides, activation of p38MAPK in primary tumors has been revealed to contribute to EMT [34], which was a biological process of the lineage transition between epithelium and mesenchyme with invasive capacities [36]. To be specific, this process included the gradual loss of some features of epithelial cells (like the deletion of E-cadherin), the loss of cellular adhesion, and the acquirement of some new features (like the increase of mesenchymal cell marker proteins, vimentin and N-cadherin) [37,38].…”

Emodin Inhibits ATP-Induced Proliferation and Migration by Suppressing P2Y Receptors in Human Lung Adenocarcinoma Cells

“…EMT is a frequent behavior which can enhance cancer cell migration and invasion [27, 28]. To determine the effect of ATP and emodin on EMT of A549 cells, we examined expression of mesenchymal markers fibronectin, Snail and epithelia marker E-cadherin.…”