Title:TGF-β in Epithelial to Mesenchymal Transition and Metastasis of Liver Carcinoma
Volume: 18
Issue: 27
Author(s): Patrick Reichl, Christine Haider, Markus Grubinger and Wolfgang Mikulits
Affiliation:
Keywords:
HCC, CCC, EMT, TGF-β, metastasis, cancer, epithelial cell types, hepatic fibrosis, liver carcinoma progression, tumor-suppressor.
Abstract: Hepatocellular carcinoma (HCC) and cholangiocellular carcinoma (CCC) represent the majority of hepatic malignancies and
are among the most frequent causes of cancer deaths worldwide with a rising incidence in western countries. Upon progression of liver
cancer, the epithelial to mesenchymal transition (EMT) is considered a key process that drives intrahepatic metastasis. EMT is the transformation
of epithelial cells to a mesenchymal phenotype exacerbating motility and invasiveness of various epithelial cell types. In this
review we focus on EMT in hepatic fibrosis, HCC and CCC that is governed by the transforming growth factor (TGF)-β signaling. This
cytokine has been shown to play diverse and conflicting roles in malignant development, acting as a tumor-suppressor in early cancerogenesis
but enhancing tumor dissemination in later stages of tumor progression. Importantly, TGF-β can induce EMT in a variety of cancers
including HCC and CCC, even though the complex molecular mechanisms underlying this process are not yet fully understood. We
aim at collecting recent findings on the impact of TGF-β-induced EMT in liver carcinoma progression and at discussing new insights on
promising drugable targets for future therapeutic approaches against CCC and HCC.