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Article

Transdifferentiation of type II alveolar epithelial cells induces reactivation of dormant tumor cells by enhancing TGF-β1/SNAI2 signaling

  • Authors:
    • Yuanhong Zhou
    • Qiang Liu
    • Xiangchen Dai
    • Yuling Yan
    • Ying Yang
    • Hua Li
    • Xiaoling Zhou
    • Wenqi Gao
    • Xiaolan Li
    • Zuyang Xi
  • View Affiliations / Copyright

    Affiliations: The First College of Clinical Medical Science, China Three Gorges University/Yichang Central People's Hospital, Yichang, Hubei 443000, P.R. China
  • Pages: 1874-1882
    |
    Published online on: February 6, 2018
       https://doi.org/10.3892/or.2018.6247
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Abstract

Dormant tumor cells (DTCs) serve a crucial role in the pathogenesis of metastasis and may compromise the efficacy of existing therapeutic modalities aimed at fully eradicating cancer. However, the mechanisms underlying the dormant-to-proliferating switch of DTCs remain largely unknown. The lung is one of the most common sites of metastatic recurrence. The transdifferentiation of alveolar epithelial cells II (AEC IIs) to AEC Is is a hallmark of alveolar epithelial stimulation. However, the role of AEC II transdifferentiation during the reactivation of DTCs has not been fully elucidated. In the present study, we found that tumor cells promoted the transdifferentiation of AEC IIs. Furthermore, the supernatant of the transdifferentiation of AEC IIs to AEC Is (Super-TDA) promoted the dormant-to-proliferating switch of DTCs via the autocrine effect of TGF-β1 on the 3D BME culture system in vitro. Monensin and LY2109761 blocked the dormant-to-proliferating switch of DTCs induced by Super-TDA. Although lipopolysaccharide did not directly stimulate the reactivation of DTCs, it promoted DTC reactivation by increasing the secretion of TGF-β1 in the Super-TDA. We further demonstrated that the upregulation of SNAI2 expression was required for Super-TDA facilitating the DTC dormant-to‑proliferating switch. Taken together, our findings demonstrated that tumor cells may promote AEC II transdifferentiation. Furthermore, the transdifferentiation of AEC IIs may, in turn, induce the reactivation of 3D-established DTCs by promoting TGF-β1/SNAI2 signaling. Targeting this process may provide novel therapeutic strategies for the inhibition of the dormant‑to-proliferating switch.
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Copy and paste a formatted citation
Spandidos Publications style
Zhou Y, Liu Q, Dai X, Yan Y, Yang Y, Li H, Zhou X, Gao W, Li X, Xi Z, Xi Z, et al: Transdifferentiation of type II alveolar epithelial cells induces reactivation of dormant tumor cells by enhancing TGF-β1/SNAI2 signaling. Oncol Rep 39: 1874-1882, 2018.
APA
Zhou, Y., Liu, Q., Dai, X., Yan, Y., Yang, Y., Li, H. ... Xi, Z. (2018). Transdifferentiation of type II alveolar epithelial cells induces reactivation of dormant tumor cells by enhancing TGF-β1/SNAI2 signaling. Oncology Reports, 39, 1874-1882. https://doi.org/10.3892/or.2018.6247
MLA
Zhou, Y., Liu, Q., Dai, X., Yan, Y., Yang, Y., Li, H., Zhou, X., Gao, W., Li, X., Xi, Z."Transdifferentiation of type II alveolar epithelial cells induces reactivation of dormant tumor cells by enhancing TGF-β1/SNAI2 signaling". Oncology Reports 39.4 (2018): 1874-1882.
Chicago
Zhou, Y., Liu, Q., Dai, X., Yan, Y., Yang, Y., Li, H., Zhou, X., Gao, W., Li, X., Xi, Z."Transdifferentiation of type II alveolar epithelial cells induces reactivation of dormant tumor cells by enhancing TGF-β1/SNAI2 signaling". Oncology Reports 39, no. 4 (2018): 1874-1882. https://doi.org/10.3892/or.2018.6247
Copy and paste a formatted citation
x
Spandidos Publications style
Zhou Y, Liu Q, Dai X, Yan Y, Yang Y, Li H, Zhou X, Gao W, Li X, Xi Z, Xi Z, et al: Transdifferentiation of type II alveolar epithelial cells induces reactivation of dormant tumor cells by enhancing TGF-β1/SNAI2 signaling. Oncol Rep 39: 1874-1882, 2018.
APA
Zhou, Y., Liu, Q., Dai, X., Yan, Y., Yang, Y., Li, H. ... Xi, Z. (2018). Transdifferentiation of type II alveolar epithelial cells induces reactivation of dormant tumor cells by enhancing TGF-β1/SNAI2 signaling. Oncology Reports, 39, 1874-1882. https://doi.org/10.3892/or.2018.6247
MLA
Zhou, Y., Liu, Q., Dai, X., Yan, Y., Yang, Y., Li, H., Zhou, X., Gao, W., Li, X., Xi, Z."Transdifferentiation of type II alveolar epithelial cells induces reactivation of dormant tumor cells by enhancing TGF-β1/SNAI2 signaling". Oncology Reports 39.4 (2018): 1874-1882.
Chicago
Zhou, Y., Liu, Q., Dai, X., Yan, Y., Yang, Y., Li, H., Zhou, X., Gao, W., Li, X., Xi, Z."Transdifferentiation of type II alveolar epithelial cells induces reactivation of dormant tumor cells by enhancing TGF-β1/SNAI2 signaling". Oncology Reports 39, no. 4 (2018): 1874-1882. https://doi.org/10.3892/or.2018.6247
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