The property of resistance to chemotherapy and irradiation treatment is the major clinical criterion to characterize ''cancer stem-like cells (CSCs)'' [6] . The existence of cancer stem-like cells may explain why conventional anti-cancer therapies are able only to suppress or shrink a tumor but often cannot completely eradicate it, resulting in eventual recurrence [6, 40, 41] . Consistent with these hypotheses, LC-CD133 + were significantly resistant to cisplatin, VP16 (eptoposide), doxorubicin, and paclitaxel than LC-CD133 2 (p,0.001; Fig. 4 ). Even IR alone or a single chemodrug can effectively inhibit cell growth of LC-CD133 2 (Fig. 4) ; however, IR treatment combined with cisplatin and VP-16 still failed to cause cell death in treated LC-CD133 + (Fig. 4D) . To overcome resistance to radiotherapy and chemotherapy in LC-CD133 + , treatment of Oct-4 siRNA was used and results showed that the knockdown Oct-4 in LC-CD133 + can significantly improve the anti-cancer effect in single-or combination-treated LC-CD133 + in vitro and in vivo (Figs. 6 and 7) . Moreover, the mean survival rate of the LC-CD133 + group can be significantly prolonged after the treatment of Oct-4 siRNA with IR and chemotherapy (Fig. 7) . Recently, Oct-4 has been suggested to be a protector for survival of ES cells from apoptosis induced by etoposide, UV, or heat shock through the Stat3/Survivin pathway [42] . Consistent with this important finding, our results suggest that knockdown of Oct-4 expression can effectively enhance the chemoradiosensitivity of LC-CD133 + through activating the apoptotic activities of caspase 3 and PARP (Fig. 6) . Importantly, our in vivo animal study and clinical data provide the evidence that the amount of Oct-4 in LC-CD133 + (Fig. 7C ) and in patients with high-grade lung cancer (Fig. S1 ) is positively correlated with the degree of resistance to chemoradiation therapy. Taken together, these results indicate that the up-regulated expression of Oct-4 in LC-CD133 + may contribute to the development of chemoradioresistance in patients with lung cancer.