Epithelial-mesenchymal transition in hepatocellular carcinoma.
The transition of epithelial cells to a mesenchymal phenotype is of paramount relevance for embryonic development and adult wound healing. During the past decade, the epithelial-mesenchymal transition (EMT) has been increasingly recognized to occur during the progression of various carcinomas such as hepatocellular carcinoma (HCC). Here, we focus on EMT in both experimental liver models and human HCC, emphasizing the underlying molecular mechanisms which show partial recurrence of embryonic programs such as TGF-beta and Wnt/ beta-catenin signaling, including collaboration with hepatitis viruses. We further discuss the differentiation repertoire of malignant hepatocytes with respect to the potential acquisition of stemness, and the involvement of the mesenchymal to epithelial transition, the reversal of EMT, in cancer dissemination and metastatic colonization. The strong evidence for EMT in HCC patients demands novel strategies in pathological assessments and therapeutic concepts to efficiently combat HCC progression.
van Zijl
Franziska
F
Department of Medicine I, Division: Institute of Cancer Research, Medical University of Vienna, Borschke-Gasse 8a, A-1090 Vienna, Austria.
Zulehner
Gudrun
G
Petz
Michaela
M
Schneller
Doris
D
Kornauth
Christoph
C
Hau
Mara
M
Machat
Georg
G
Grubinger
Markus
M
Huber
Heidemarie
H
Mikulits
Wolfgang
W
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000473:pathology*; D054337:Cell Dedifferentiation / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology*; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000473:pathology*; D004848:Epithelium / Q000473:pathology*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology*; D008648:Mesoderm / Q000473:pathology; D008679:Metaplasia