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Medical Oncology

, 32:95 | Cite as

Wnt signaling regulates the stemness of lung cancer stem cells and its inhibitors exert anticancer effect on lung cancer SPC-A1 cells

  • Xueyan Zhang
  • Yuqing Lou
  • Huimin Wang
  • Xiaoxuan Zheng
  • Qianggang Dong
  • Jiayuan Sun
  • Baohui HanEmail author
Original Paper

Abstract

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.

Keywords

Functional genome screening Lung cancer stem cells Pluripotent stem cell markers Sphere culture Wnt signaling pathway 

Notes

Acknowledgments

This work was funded by Shanghai Natural Science Foundation (No. 13ZR1438600).

Conflict of interest

None.

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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Xueyan Zhang
    • 1
  • Yuqing Lou
    • 1
  • Huimin Wang
    • 1
  • Xiaoxuan Zheng
    • 1
  • Qianggang Dong
    • 2
  • Jiayuan Sun
    • 1
  • Baohui Han
    • 1
    Email author
  1. 1.Department of Pulmonary Medicine, Shanghai Chest HospitalShanghai Jiao Tong UniversityShanghaiChina
  2. 2.Section of Cancer Stem Cells, Shanghai Cancer InstituteShanghai Jiao Tong UniversityShanghaiChina

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