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.
Department of Medicine I, Division: Institute of Cancer Research, Medical University of Vienna, Borschke-Gasse 8a, A-1090 Vienna, Austria.
Franziska
F
van Zijl
Gudrun
G
Zulehner
Michaela
M
Petz
Doris
D
Schneller
Christoph
C
Kornauth
Mara
M
Hau
Georg
G
Machat
Markus
M
Grubinger
Heidemarie
H
Huber
Wolfgang
W
Mikulits
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