TGF-β in epithelial to mesenchymal transition and metastasis of liver carcinoma.
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.
Department of Medicine I, Division: Institute of Cancer Research, Comprehensive Cancer Center Vienna, Medical University of Vienna, Austria.
Patrick
P
Reichl
Christine
C
Haider
Markus
M
Grubinger
Wolfgang
W
Mikulits
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology / Q000473:pathology; D018281:Cholangiocarcinoma / Q000453:epidemiology / Q000473:pathology; D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D006801:Humans; D008103:Liver Cirrhosis / Q000473:pathology; D008113:Liver Neoplasms / Q000453:epidemiology / Q000473:pathology*; D009362:Neoplasm Metastasis; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D016212:Transforming Growth Factor beta