Department of Chemotherapy, Cancer Center, Shandong University, Jinan 250012, China.
Biochem Biophys Res Commun. 2010 Feb 12;392(3):373-9. doi: 10.1016/j.bbrc.2010.01.028. Epub 2010 Jan 13.
Wnt/beta-catenin signaling plays an important role not only in cancer, but also in cancer stem cells. In this study, we found that beta-catenin and OCT-4 was highly expressed in cisplatin (DDP) selected A549 cells. Stimulating A549 cells with lithium chloride (LiCl) resulted in accumulation of beta-catenin and up-regulation of a typical Wnt target gene cyclin D1. This stimulation also significantly enhanced proliferation, clone formation, migration and drug resistance abilities in A549 cells. Moreover, the up-regulation of OCT-4, a stem cell marker, was observed through real-time PCR and Western blotting. In a reverse approach, we inhibited Wnt signaling by knocking down the expression of beta-catenin using RNA interference technology. This inhibition resulted in down-regulation of the Wnt target gene cyclin D1 as well as the proliferation, clone formation, migration and drug resistance abilities. Meanwhile, the expression of OCT-4 was reduced after the inhibition of Wnt/beta-catenin signaling. Taken together, our study provides strong evidence that canonical Wnt signaling plays an important role in lung cancer stem cell properties, and it also regulates OCT-4, a lung cancer stem cell marker.
Wnt/β-catenin 信号通路不仅在癌症中发挥重要作用，而且在癌症干细胞中也发挥重要作用。在这项研究中，我们发现β-catenin 和 OCT-4 在顺铂（DDP）选择的 A549 细胞中高表达。用氯化锂（LiCl）刺激 A549 细胞导致β-catenin 积累和典型 Wnt 靶基因 cyclin D1 的上调。这种刺激还显著增强了 A549 细胞的增殖、克隆形成、迁移和耐药能力。此外，通过实时 PCR 和 Western blot 观察到干细胞标志物 OCT-4 的上调。在反向方法中，我们通过 RNA 干扰技术敲低β-catenin 的表达来抑制 Wnt 信号通路。这种抑制导致 Wnt 靶基因 cyclin D1 的下调以及增殖、克隆形成、迁移和耐药能力的降低。同时，抑制 Wnt/β-catenin 信号通路后，OCT-4 的表达减少。综上所述，我们的研究提供了强有力的证据表明经典 Wnt 信号通路在肺癌干细胞特性中发挥重要作用，并且它还调节 OCT-4，一种肺癌干细胞标志物。
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