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Inhibition of GSK3 and MEK induced cancer stem cell generation via the Wnt and MEK signaling pathways

  • Authors:
    • Shengtao Liao
    • Li Gan
    • Wanxiang Qin
    • Chang Liu
    • Zhechuan Mei
  • View Affiliations / Copyright

    Affiliations: Department of Gastroenterology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, P.R. China, Teaching and Research Section of Forensic Medicine, College of Basic Medicine, Chongqing Medical University, Chongqing 400016, P.R. China, Department of Pain Management, Southwest Hospital, The First Affiliated Hospital of The Third Military Medical University, Chongqing 400038, P.R. China, Institute of Medicine and Hygienic Equipment for High Altitude Region, College of High Altitude Military Medicine, Third Military Medical University, Chongqing 400038, P.R. China
    Copyright: © Liao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 2005-2013
    |
    Published online on: July 25, 2018
       https://doi.org/10.3892/or.2018.6600
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Abstract

Cancer stem cells (CSCs) are considered to be tumor‑initiating cells, responsible for tumor invasive growth and dissemination to distant organ sites. Typically, radiation treatment and chemotherapy should target CSCs. However, current research investigating CSCs is impeded by the difficulty of isolating pure CSCs and maintaining them in vitro. In the present study, the synergistic inhibition of glycogen synthase kinase 3 and mitogen‑activated protein kinase kinase using small molecules, CHIR99021 and PD184352, efficiently generated CSCs from immortalized human mammary epithelial cells (HMLEs) and resulted in the acquisition of mesenchymal traits and the expression of epithelial‑mesenchymal transition markers. The cell proliferation, invasion and migration of HMLE cells were significantly promoted by CHIR99021 and PD184352 (P<0.05). Furthermore, the cell cycle was shifted from the G0/G1 phase to the G2/M phase, and the apoptotic rate was suppressed in HMLE cells following treatment with CHIR99021 and PD184352. Compared with control group, the stimulated cells exhibited an increased ability to form mammospheres and regenerate a tumor. In addition to these properties, the induced cells also exhibited notable chemotherapy resistance. In vivo, the treatment of cells with CHIR99021 and PD184352 promoted the growth of HMLE‑engrafted tumor types. These results provide a practical strategy for the generation of CSCs using small molecules in vitro, which provides a cell resource that may be used for drug screening. Additionally, the present results additionally highlighted the synergistic functions of Wnt and mitogen‑activated protein kinase kinase signaling pathways in tumorigenesis.
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Copy and paste a formatted citation
Spandidos Publications style
Liao S, Gan L, Qin W, Liu C and Mei Z: Inhibition of GSK3 and MEK induced cancer stem cell generation via the Wnt and MEK signaling pathways. Oncol Rep 40: 2005-2013, 2018.
APA
Liao, S., Gan, L., Qin, W., Liu, C., & Mei, Z. (2018). Inhibition of GSK3 and MEK induced cancer stem cell generation via the Wnt and MEK signaling pathways. Oncology Reports, 40, 2005-2013. https://doi.org/10.3892/or.2018.6600
MLA
Liao, S., Gan, L., Qin, W., Liu, C., Mei, Z."Inhibition of GSK3 and MEK induced cancer stem cell generation via the Wnt and MEK signaling pathways". Oncology Reports 40.4 (2018): 2005-2013.
Chicago
Liao, S., Gan, L., Qin, W., Liu, C., Mei, Z."Inhibition of GSK3 and MEK induced cancer stem cell generation via the Wnt and MEK signaling pathways". Oncology Reports 40, no. 4 (2018): 2005-2013. https://doi.org/10.3892/or.2018.6600
Copy and paste a formatted citation
x
Spandidos Publications style
Liao S, Gan L, Qin W, Liu C and Mei Z: Inhibition of GSK3 and MEK induced cancer stem cell generation via the Wnt and MEK signaling pathways. Oncol Rep 40: 2005-2013, 2018.
APA
Liao, S., Gan, L., Qin, W., Liu, C., & Mei, Z. (2018). Inhibition of GSK3 and MEK induced cancer stem cell generation via the Wnt and MEK signaling pathways. Oncology Reports, 40, 2005-2013. https://doi.org/10.3892/or.2018.6600
MLA
Liao, S., Gan, L., Qin, W., Liu, C., Mei, Z."Inhibition of GSK3 and MEK induced cancer stem cell generation via the Wnt and MEK signaling pathways". Oncology Reports 40.4 (2018): 2005-2013.
Chicago
Liao, S., Gan, L., Qin, W., Liu, C., Mei, Z."Inhibition of GSK3 and MEK induced cancer stem cell generation via the Wnt and MEK signaling pathways". Oncology Reports 40, no. 4 (2018): 2005-2013. https://doi.org/10.3892/or.2018.6600
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