The possible existence of plasticity between cancer stem cells and their more differentiated derivative cancer cells was suggested. We successfully induced cancer stem-like sphere cells from human HCC cell lines with specified medium. Poorly differentiated HCC derived SK-HEP-1 and undifferentiated HCC derived HLE cell lines efficiently formed spheres (SK-sphere and HLE-sphere). In the presence of several anti-cancer drugs except sorafenib, the cell viability of SK-sphere and HLE-sphere were significantly higher than that of parental cells. SK-sphere showed higher HIF1A mRNA expression, more CD44 variant-positive cells, and lower ROS production compared to parental cells. Integrated analysis showed that HIF1A and its downstream genes were up-regulated in SK-sphere. Finally, e identified several new marker and therapy target candidates (mRNA, microRNA, and protein) to cancer stem cells by integrated omics analysis.
