Wnt signaling regulates the stemness of lung cancer stem cells and its inhibitors exert anticancer effect on lung cancer SPC-A1 cells.
Wnt signaling plays an important role in regulating the activity of cancer stem cells (CSCs) in a variety of cancers. In this study, we explored the role of Wnt signaling in the lung cancer stem cells (LCSCs). LCSCs were obtained by sphere culture, for which human lung adenocarcinoma cell line SPC-A1 was treated with IGF, EGF and FGF-10. The stemness of LCSCs was confirmed by immunofluorescence, and pathway analysis was performed by functional genome screening and RT-PCR. The relationship between the identified signaling pathway and the expression of the stemness genes was explored by agonist/antagonist assay. Moreover, the effects of different signaling molecule inhibitors on sphere formation, cell viability and colony formation were also analyzed. The results showed that LCSCs were successfully generated as they expressed pluripotent stem cell markers Nanog and Oct 4, and lung distal epithelial markers CCSP and SP-C, by which the phenotype characterization of stem cells can be confirmed. The involvement of Wnt pathway in LCSCs was identified by functional genome screening and verified by RT-PCR. The expression of Wnt signaling components was closely related to the expression of the Nanog and Oct 4. Furthermore, targeting Wnt signaling pathway by using different signaling molecule inhibitors can exert anticancer effects. In conclusion, Wnt signaling pathway is involved in the stemness regulation of LCSCs and might be considered as a potential therapeutic target in lung adenocarcinoma.
Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, 241 West Huaihai Road, Shanghai, 200000, China.
Xueyan
X
Zhang
Yuqing
Y
Lou
Huimin
H
Wang
Xiaoxuan
X
Zheng
Qianggang
Q
Dong
Jiayuan
J
Sun
Baohui
B
Han
D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D005455:Fluorescent Antibody Technique; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D051153:Wnt Proteins / Q000819:agonists* / Q000037:antagonists & inhibitors*
D000970:Antineoplastic Agents; D012333:RNA, Messenger; D051153:Wnt Proteins