Self-renewal and pluripotency are the central features in the definition of embryonic stem cells (ESC), and Oct-4 is a key regulator in this process [24] [25] [26] . Oct-4 has been suggested as one of four major factors that render the reprogramming capability of adult cells into germline-competent-induced pluripotent stem cells [31] [32] [33] . Previous studies also showed that mouse pulmonary stem cells endogenously express Oct-4 [34] . Recently, Oct-4 transcript can be consistently detected in human embryonal carcinomas, testicular germ cell tumors, seminomas, and bladder carcinomas [35] [36] [37] [38] . The expression of Oct-4 has further been shown in human breast cancer stem-like cells, suggesting that its expression may be implicated in self-renewal and tumorigenesis via activating its downstream target genes [39] . Herein we reported the isolation of CD133-positive cells (LC-CD133 + ) from clinical tissue samples and lung cancer cell lines. LC-CD133 + showed strong proliferative and invasive capabilities in vitro and in vivo (Figs. 1, 2, and 3) . LC-CD133 + also displayed significant resistance to chemotherapeutic agents (Fig. 4) . We also demonstrated that Oct-4 expression was transcriptionally and translationally up-regulated in LC-CD133 + (Fig. 5) . Indeed, Oct-4 functions as a master switch during differentiation by regulating the pluripotent potential in stem cells [31] [32] [33] . Using the siRNA method with lentiviral vector for knockdown of Oct-4 expression in LC-CD133 + , our data showed that the treatment of Oct-4 siRNA can block the sphere formation of LC-CD133 + and further facilitate LC-CD133 + to differentiate into LC-CD133 2 (Fig. 5) . Furthermore, in vivo animal studies demonstrated the IHC of Oct-4 in the lung tumors of LC-CD133 + -injected SCID mice were prominently up-regulated, and the total lung tumor volume as well as Oct-4 IHC levels can be significantly decreased in LC-CD133 + -injected mice by the treatment of Oct-4 siRNA with or without chemoradiotherapy (Fig. 7) . In addition, we showed that increased incidence of Oct-4 expression correlated positively with the advanced stage of 78 lung cancers (Figs. S1A-C). To our knowledge, this is the first study to show that Oct-4 expression plays a crucial role in maintaining selfrenewal and cancer stem-like properties in LC-CD133 + .