Wnt/beta-catenin signaling regulates cancer stem cells in lung cancer A549 cells.
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.
Teng
Ying
Y
Department of Chemotherapy, Cancer Center, Shandong University, Jinan 250012, China.
Wang
Xiuwen
X
Wang
Yawei
Y
Ma
Daoxin
D
D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D055785:Gene Knockdown Techniques; D006801:Humans; D018021:Lithium Chloride / Q000494:pharmacology; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000502:physiology*; D050814:Octamer Transcription Factor-3 / Q000378:metabolism; D015398:Signal Transduction; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
C495270:CTNNB1 protein, human; D050814:Octamer Transcription Factor-3; D051153:Wnt Proteins; D051176:beta Catenin; D019938:Cyclin D1; D018021:Lithium Chloride