@Article{096504016X14685034103950,
AUTHOR = {Su-Hoon Lee, Suh-Kyung Hyun, Hak-Bong Kim, Chi-Dug Kang, Sun-Hee Kim},
TITLE = {Potential Role of CD133 Expression in the Susceptibility of Human Liver  Cancer Stem-Like Cells to TRAIL},
JOURNAL = {Oncology Research},
VOLUME = {24},
YEAR = {2016},
NUMBER = {6},
PAGES = {495--509},
URL = {http://www.techscience.com/or/v24n6/57007},
ISSN = {1555-3906},
ABSTRACT = {Hepatocellular carcinoma (HCC) is one of the most common malignancies, with a poor prognosis and high 
recurrence rate. In the present study, we identified CD133, one of the markers of cancer stem cells, as a novel 
molecular target of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). In four human HCC cell 
lines established from primary HCC tumors, we found that CD133-high human liver cancer stem-like cells 
(CD133<sup>hi</sup>) derived from the SNU-475 cell line were highly susceptible to TRAIL compared to other HCC cell 
lines with a small population of CD133. CD133<sup>hi</sup> SNU-475 cells showed upregulation of TRAIL receptor DR5 
and stemness-related genes such as c-Myc and ABC transporters compared to their CD133-low (CD133lo) 
cells. Hypersensitivity of CD133<sup>hi</sup> cells to TRAIL was associated with c-Myc-mediated upregulation of DR5 
and downregulation of c-FLIPL in the cells. Knockdown of CD133 expression in CD133<sup>hi</sup> cells resulted in the 
downregulation of c-Myc, and depletion of c-Myc caused a decrease in the cell surface expression of DR5 
and an increase in the expression of c-FLIPL and, consequently, attenuated TRAIL-induced cytotoxicity and 
apoptosis of CD133<sup>hi</sup> cells. These results suggest that TRAIL may provide a new strategy for CD133<sup>hi</sup> CSCs of 
HCC-targeted therapies and, potentially, for therapies of other CD133-expressing types of cancer.},
DOI = {10.3727/096504016X14685034103950}
}