Gene Set: YAMASHITA_LIVER_CANCER_STEM_CELL_DN

Standard name YAMASHITA_LIVER_CANCER_STEM_CELL_DN
Systematic name M9206
Brief description Genes down-regulated in hepatocellular carcinoma (HCC) cells with hepatic stem cell properties.
Full description or abstract BACKGROUND & AIMS: Cancer progression/metastases and embryonic development share many properties including cellular plasticity, dynamic cell motility, and integral interaction with the microenvironment. We hypothesized that the heterogeneous nature of hepatocellular carcinoma (HCC), in part, may be owing to the presence of hepatic cancer cells with stem/progenitor features. METHODS: Gene expression profiling and immunohistochemistry analyses were used to analyze 235 tumor specimens derived from 2 recently identified HCC subtypes (EpCAM(+) alpha-fetoprotein [AFP(+)] HCC and EpCAM(-) AFP(-) HCC). These subtypes differed in their expression of AFP, a molecule produced in the developing embryo, and EpCAM, a cell surface hepatic stem cell marker. Fluorescence-activated cell sorting was used to isolate EpCAM(+) HCC cells, which were tested for hepatic stem/progenitor cell properties. RESULTS: Gene expression and pathway analyses revealed that the EpCAM(+) AFP(+) HCC subtype had features of hepatic stem/progenitor cells. Indeed, the fluorescence-activated cell sorting-isolated EpCAM(+) HCC cells displayed hepatic cancer stem cell-like traits including the abilities to self-renew and differentiate. Moreover, these cells were capable of initiating highly invasive HCC in nonobese diabetic, severe combined immunodeficient mice. Activation of Wnt/beta-catenin signaling enriched the EpCAM(+) cell population, whereas RNA interference-based blockage of EpCAM, a Wnt/beta-catenin signaling target, attenuated the activities of these cells. CONCLUSIONS: Taken together, our results suggest that HCC growth and invasiveness is dictated by a subset of EpCAM(+) cells, opening a new avenue for HCC cancer cell eradication by targeting Wnt/beta-catenin signaling components such as EpCAM.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 19150350   Authors: Yamashita T,Ji J,Budhu A,Forgues M,Yang W,Wang HY,Jia H,Ye Q,Qin LX,Wauthier E,Reid LM,Minato H,Honda M,Kaneko S,Tang ZY,Wang XW
Exact source Table 3S, 4S: Down
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Organism Homo sapiens
Contributed by Yujin Hoshida (Broad Institute)
Source platform HUMAN_GENE_SYMBOL
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Compendia expression profiles Human tissue compendium (Novartis)
NCI-60 cell lines (National Cancer Institute)
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Version history 3.0: First introduced

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