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Article

Preliminary mechanisms of regulating PD‑L1 expression in non‑small cell lung cancer during the EMT process

  • Authors:
    • Fang Li
    • Tengjiao Zhu
    • Yao Yue
    • Xiang Zhu
    • Jiadong Wang
    • Li Liang
  • View Affiliations / Copyright

    Affiliations: Department of Tumor Chemotherapy and Radiation Sickness, Peking University Third Hospital, Beijing 100191, P.R. China, Orthopedic Department, Peking University International Hospital, Beijing 102206, P.R. China, Department of Radiation Medicine, School of Basic Medical Science, Peking University, Beijing 100191, P.R. China, Department of Pathology, Peking University Third Hospital, Beijing 100191, P.R. China, Department of Tumor Chemotherapy and Radiation Sickness, Peking University Third Hospital, Beijing 100191, P.R. China
  • Pages: 775-782
    |
    Published online on: June 5, 2018
       https://doi.org/10.3892/or.2018.6474
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Abstract

Non‑small cell lung cancer (NSCLC) is one of the most severe malignant tumor types worldwide. Recent studies have reported an important role of PD‑L1 in mediating immune evasion in the tumor microenvironment. In addition, increasing research has indicated that the expression of PD‑L1 is related to the epithelial‑mesenchymal transition (EMT) process, but the related mechanisms remain to be explored. In the present study, we explored the molecular mechanisms underlying the regulation of PD‑L1 expression during the EMT process in NSCLC cells treated with transforming growth factor‑β1 (TGF‑β1) and fibroblast growth factor 2 (FGF2). The phenotypic alteration associated with EMT was evaluated by western blotting and confirmed by a wound‑healing assay. The results revealed that EMT markedly promoted the expression of PD‑L1 in the A549 cell line, while having no obvious influence on the H1650 and H1975 cells. Furthermore, the AKT pathway inhibitor LY294002, the ERK pathway inhibitor PD98059 and the TAK1 pathway inhibitor 5Z‑7 inhibited the expression of PD‑L1 in A549 and H1650 cells, but not in H1975 cells, during the EMT process. Moreover, our study indicated that the AKT, ERK and TAK1 pathways regulated the expression of PD‑L1 by mediating transportation of the transcription factor Stat3 and the p65 subunit of NF‑κB from the cytoplasm to the nucleus, with such findings determined by western blotting and flow cytometric analyses. Furthermore, the expression of PD‑L1 was significantly increased following treatment with gefitinib in a tumor xenograft model. In summary, our results support the role of ERK, AKT and TAK1 in mediating the expression of PD‑L1 during the EMT process, and indicate a promising strategy of PD‑L1‑targeted therapy for the clinical treatment of NSCLC.
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Copy and paste a formatted citation
Spandidos Publications style
Li F, Zhu T, Yue Y, Zhu X, Wang J and Liang L: Preliminary mechanisms of regulating PD‑L1 expression in non‑small cell lung cancer during the EMT process. Oncol Rep 40: 775-782, 2018.
APA
Li, F., Zhu, T., Yue, Y., Zhu, X., Wang, J., & Liang, L. (2018). Preliminary mechanisms of regulating PD‑L1 expression in non‑small cell lung cancer during the EMT process. Oncology Reports, 40, 775-782. https://doi.org/10.3892/or.2018.6474
MLA
Li, F., Zhu, T., Yue, Y., Zhu, X., Wang, J., Liang, L."Preliminary mechanisms of regulating PD‑L1 expression in non‑small cell lung cancer during the EMT process". Oncology Reports 40.2 (2018): 775-782.
Chicago
Li, F., Zhu, T., Yue, Y., Zhu, X., Wang, J., Liang, L."Preliminary mechanisms of regulating PD‑L1 expression in non‑small cell lung cancer during the EMT process". Oncology Reports 40, no. 2 (2018): 775-782. https://doi.org/10.3892/or.2018.6474
Copy and paste a formatted citation
x
Spandidos Publications style
Li F, Zhu T, Yue Y, Zhu X, Wang J and Liang L: Preliminary mechanisms of regulating PD‑L1 expression in non‑small cell lung cancer during the EMT process. Oncol Rep 40: 775-782, 2018.
APA
Li, F., Zhu, T., Yue, Y., Zhu, X., Wang, J., & Liang, L. (2018). Preliminary mechanisms of regulating PD‑L1 expression in non‑small cell lung cancer during the EMT process. Oncology Reports, 40, 775-782. https://doi.org/10.3892/or.2018.6474
MLA
Li, F., Zhu, T., Yue, Y., Zhu, X., Wang, J., Liang, L."Preliminary mechanisms of regulating PD‑L1 expression in non‑small cell lung cancer during the EMT process". Oncology Reports 40.2 (2018): 775-782.
Chicago
Li, F., Zhu, T., Yue, Y., Zhu, X., Wang, J., Liang, L."Preliminary mechanisms of regulating PD‑L1 expression in non‑small cell lung cancer during the EMT process". Oncology Reports 40, no. 2 (2018): 775-782. https://doi.org/10.3892/or.2018.6474
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