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An Application of Photoactivatable Substrate for the Evaluation of Epithelial-mesenchymal Transition Inhibitors

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Abstract

Epithelial-mesenchymal transition (EMT), phenotypic changes in cell adhesion and migration, is involved in cancer invasion and metastasis, hence becoming a target for anti-cancer drugs. In this study, we report a method for the evaluation of EMT inhibitors by using a photoactivatable gold substrate, which changes from non-cell-adhesive to celladhesive in response to light. The method is based on the geometrical confinement of cell clusters and the subsequent migration induction by controlled photoirradiation of the substrate. As a proof-of-concept experiment, a known EMT inhibitor was successfully evaluated in terms of the changes in cluster area or leader cell appearance, in response to biochemically and mechanically induced EMT. Furthermore, an application of the present method for microbial secondary metabolites identified nanaomycin H as an EMT inhibitor, potentially killing EMTed cells in disseminated conditions. These results demonstrate the potential of the present method for screening new EMT inhibitors.

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Acknowledgments

This study was supported in part by the Japan Society for Promotion of Science, Kakenhi (No. 18H02010 and 18K19946). We thank to Prof. Kazuo Yamaguchi (Kanagawa Univ.) for the photocleavable disulfide molecule.

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Authors and Affiliations

  1. International Center for Materials Nanoarchitectonics (WPI-MANA), National Institute for Materials Science (NIMS), 1-1 Namiki, Tsukuba, Ibaraki, 305-0044, Japan

    Jun Nakanishi & Kenji Sugiyama

  2. Kitasato Institute for Life Sciences, Kitasato University, 5-9-1 Shirokane, Minato, Tokyo, 108-8641, Japan

    Hirotaka Matsuo, Yoko Takahashi, Satoshi Ōmura & Takuji Nakashima

  3. Graduate School of Infection Control Sciences, Kitasato University, 5-9-1 Shirokane, Minato, Tokyo, 108-8641, Japan

    Hirotaka Matsuo & Takuji Nakashima

Authors
  1. Jun Nakanishi
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  2. Kenji Sugiyama
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  3. Hirotaka Matsuo
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  4. Yoko Takahashi
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  5. Satoshi Ōmura
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  6. Takuji Nakashima
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Correspondence to Jun Nakanishi.

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Nakanishi, J., Sugiyama, K., Matsuo, H. et al. An Application of Photoactivatable Substrate for the Evaluation of Epithelial-mesenchymal Transition Inhibitors. ANAL. SCI. 35, 65–69 (2019). https://doi.org/10.2116/analsci.18SDP07

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  • DOI: https://doi.org/10.2116/analsci.18SDP07

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