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Review
. 2013 May;123(5):1911-8.
doi: 10.1172/JCI66024. Epub 2013 May 1.

Cancer stem cells in the development of liver cancer

Taro Yamashita  1 , Xin Wei Wang
Affiliations
Review

Cancer stem cells in the development of liver cancer

Taro Yamashita et al. J Clin Invest. 2013 May.

Abstract

Liver cancer is an aggressive disease with a poor outcome. Several hepatic stem/progenitor markers are useful for isolating a subset of liver cells with stem cell features, known as cancer stem cells (CSCs). These cells are responsible for tumor relapse, metastasis, and chemoresistance. Liver CSCs dictate a hierarchical organization that is shared in both organogenesis and tumorigenesis. An increased understanding of the molecular signaling events that regulate cellular hierarchy and stemness, and success in defining key CSC-specific genes, have opened up new avenues to accelerate the development of novel diagnostic and treatment strategies. This Review highlights recent advances in understanding the pathogenesis of liver CSCs and discusses unanswered questions about the concept of liver CSCs.

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Figures

Figure 1
Figure 1. Liver inflammation and regeneration in liver CSC development.
Stem/progenitor cells expand in CLD as a result of impaired hepatocyte replication, and genetic and epigenetic changes potentially accumulate in all liver lineages. Activation of stromal cells may induce various signaling pathways, including cytokines such as Wnt, FGF, PDGF, VEGF, and TGF-β, and promote the development of liver CSCs.
Figure 2
Figure 2. Potential origin and evolution of liver CSCs.
CSCs may originate from non-CSCs by the activation of dedifferentiation programs. Liver CSC development may be regulated by hepatobiliary lineage commitment programs and oncogenic programs that are induced by acquired by genetic/epigenetic changes and activated signaling pathways. The emergence and domination of liver CSCs may reflect the molecular subtypes of liver cancers linked to the clinical outcome. CCA, cholangiocellular carcinoma.
See this image and copyright information in PMC

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