Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2009 Oct;5(8):1169-79.
doi: 10.2217/fon.09.91.

Epithelial-mesenchymal transition in hepatocellular carcinoma

Franziska van Zijl  1 , Gudrun Zulehner, Michaela Petz, Doris Schneller, Christoph Kornauth, Mara Hau, Georg Machat, Markus Grubinger, Heidemarie Huber, Wolfgang Mikulits
Affiliations
Review

Epithelial-mesenchymal transition in hepatocellular carcinoma

Franziska van Zijl et al. Future Oncol. 2009 Oct.

Abstract

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.

PubMed Disclaimer

Figures

Figure 1
Figure 1
The involvement of EMT in physiological and pathophysiological events.
Figure 2
Figure 2. TGF-β causes EMT of malignant hepatocytes in cooperation with oncogenic Ras activation
TGF-β, transforming growth factor-β.
Figure 3
Figure 3. Poorly differentiated human HCC show loss of epithelial markers such as plasma membrane-bound E-cadherin, suggesting EMT
Human HCC samples were immunohistochemically stained with anti-E-cadherin (E-cadherin) antibody. Differentiated HCC (histological grading G1) show E-cadherin at cell boundaries, whereas poorly differentiated human HCC (histological grading G3) show loss or cytoplasmic dislocation of E-cadherin expression at plasma membranes. Black boxes indicate regions at 4-fold magnification. Two representative HCC samples are shown. Bar, 50 μm.
Figure 4
Figure 4. The putative EMT-MET cycle suggests transient and reversible changes in the epithelial plasticity during tumor progression
MET, mesenchymal to epithelial transition.
See this image and copyright information in PMC

References

    1. El-Serag HB, Rudolph KL. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology. 2007;132:2557–2776. - PubMed
    1. Kensler TW, Qian GS, Chen JG, Groopman JD. Translational strategies for cancer prevention in liver. Nat Rev Cancer. 2003;3:321–329. - PubMed
    1. Farazi PA, DePinho RA. Hepatocellular carcinoma pathogenesis: from genes to environment. Nat Rev Cancer. 2006;6:674–687. - PubMed
    1. Friedman SL. Mechanisms of hepatic fibrogenesis. Gastroenterology. 2008;134:1655–1669. - PMC - PubMed
    1. Jou J, Choi SS, Diehl AM. Mechanisms of disease progression in nonalcoholic fatty liver disease. Semin Liver Dis. 2008;28:370–379. - PubMed

Publication types

MeSH terms