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Inhibition of yes-associated protein suppresses migration, invasion, and metastasis in non-small cell lung cancer in vitro and in vivo

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Abstract

Non-small cell lung cancer (NSCLC) is a highly aggressive cancer with one of the most prevalent malignant tumors. Metastasis in NSCLC is the major cause of treatment failure and cancer-related deaths. Yes-associated protein (YAP) is a transcriptional coactivator regulated by the evolutionarily conserved Hippo signaling pathway that regulates organ size, growth, and regeneration. YAP is highly expressed in several malignant tumor types. Furthermore, YAP promotes tumor initiation and/or progression in various types of cancer. However, it is unclear whether YAP contributes to the metastasis in NSCLC and serves as a useful therapeutic target. Here, we investigated whether levels of YAP correlate with metastatic phenotype in NSCLC cells and serve as a useful therapeutic target. We found that high levels of YAP associate with high cell migration, invasion, and metastasis in NSCLC cell lines. Furthermore, YAP siRNA decreased the migration and invasion in NSCLC cells. Additionally, verteporfin, an agent used for the treatment of symptomatic polypoidal choroidal vasculopathy, decreased the expression of YAP and inhibited migration, invasion, and metastasis in NSCLC cells. Thus, the study suggests that targeting YAP may present a new avenue to develop therapeutics against metastasis in NSCLC and that verteporfin has potential molecular therapeutic strategy for the treatment of metastatic NSCLC.

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Acknowledgements

This study was supported in part by a Grant-in-Aid for Young Scientists from the Japan Society for the Promotion of Science (JSPS).

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Authors and Affiliations

  1. Division of Pharmacotherapy, Kindai University School of Pharmacy, 3-4-1 Kowakae, Higashi-Osaka, 577–8502, Japan

    Tomoya Takeda, Masanobu Tsubaki, Shuji Genno, Takuya Matsuda, Yuuta Yamamoto, Akihiro Kimura, Nao Shimizu & Shozo Nishida

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  1. Tomoya Takeda
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  2. Masanobu Tsubaki
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  3. Shuji Genno
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  4. Takuya Matsuda
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  7. Nao Shimizu
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  8. Shozo Nishida
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Contributions

T.T. performed the analysis of the RNA interference, trypan blue exclusion assay, cell migration and invasion assays, and in vivo metastasis model and drafted the manuscript. M.T. and S.G. performed the analysis of the Trypan blue exclusion assay, cell migration and invasion assays, western blotting analysis, and statistical analysis. T.M., A.K., and N.S. carried out analysis of the RNA interference, cell migration and invasion assays, western blotting analysis, and in vivo metastasis model. S.N. designed the experiments and revised the manuscript. All authors have read and approved the final manuscript.

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Correspondence to Shozo Nishida.

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The authors declare that they have no conflict of interest.

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We perform the in vivo animal studies in accordance with the Recommendations for Handling of Laboratory Animals for Biomedical Research compiled by the Committee on Safety and Ethical Handling Regulations for Laboratory Animal Experiments, Kindai University and the United Kingdom Coordinating Committee for Cancer Research (UKCCCR) guidelines.

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Takeda, T., Tsubaki, M., Genno, S. et al. Inhibition of yes-associated protein suppresses migration, invasion, and metastasis in non-small cell lung cancer in vitro and in vivo. Clin Exp Med 22, 221–228 (2022). https://doi.org/10.1007/s10238-021-00738-4

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  • DOI: https://doi.org/10.1007/s10238-021-00738-4

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