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PolyI:C suppresses TGF-β1-induced Akt phosphorylation and reduces the motility of A549 lung carcinoma cells

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Abstract

Backgrounds

Epithelial mesenchymal transition (EMT) is a critical process involved in the invasion and metastasis of cancer, including lung cancer (LC). Transforming growth factor (TGF)-β is one of factors capable of inducing EMT. Polyinosinic-polycytidylic acid (polyI:C), a synthetic agonist for toll-like receptor (TLR) 3, can enhance immune responses and has been used as an adjuvant for cancer vaccines; however, it remains unclear whether it influences other process, such as EMT. In the present study, we examined the effects of polyI:C on TGF-β-treated A549 human LC cells.

Methods and results

By in vitro cell proliferation assay, polyI:C showed no effect on the growth of A549 cells treated with TGF-β1 at the concentration range up to 10 μg/ml; however, it markedly suppressed the motility in a cell scratch and a cell invasion assay. By Western blotting, polyI:C dramatically decreased TGF-β1-induced Ak strain transforming (Akt) phosphorylation and increased phosphatase and tensin homologue (PTEN) expression without affecting the Son of mothers against decapentaplegic (Smad) 3 phosphorylation or the expression level of E-cadherin, N-cadherin or Snail, indicating that polyI:C suppressed cell motility independently of the ‘cadherin switching’. The Akt inhibitor perifosine inhibited TGF-β1-induced cell invasion, and the PTEN-specific inhibitor VO-OHpic appeared to reverse the inhibitory effect of polyI:C.

Conclusion

PolyI:C has a novel function to suppress the motility of LC cells undergoing EMT by targeting the phosphatidylinositol 3-kinase/Akt pathway partly via PTEN and may prevent or reduce the metastasis of LC cells.

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Acknowledgements

We are grateful to the members of the Department of Pathology and Experimental Medicine, Okayama University, for their useful discussion.

Funding

This study was funded by the Department of Pathology and Experimental Medicine, Okayama University.

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Authors and Affiliations

  1. Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata, Kita-ku, Okayama, 700-8558, Japan

    Takahiro Yamaguchi, Teizo Yoshimura, Toshiaki Ohara, Masayoshi Fujisawa, Gao Tong & Akihiro Matsukawa

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  1. Takahiro Yamaguchi
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  2. Teizo Yoshimura
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  3. Toshiaki Ohara
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  4. Masayoshi Fujisawa
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  5. Gao Tong
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  6. Akihiro Matsukawa
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Contributions

Conceptualization: TY; Formal analysis and investigation: TY, GT; Writing—TY, TY; Writing—review and editing: TY, TO, MF, AM; Funding acquisition: MF, TO, AM.

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Correspondence to Akihiro Matsukawa.

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Yamaguchi, T., Yoshimura, T., Ohara, T. et al. PolyI:C suppresses TGF-β1-induced Akt phosphorylation and reduces the motility of A549 lung carcinoma cells. Mol Biol Rep 48, 6313–6321 (2021). https://doi.org/10.1007/s11033-021-06625-1

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  • DOI: https://doi.org/10.1007/s11033-021-06625-1

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