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Type I collagen-induced YAP nuclear expression promotes primary cilia growth and contributes to cell migration in confluent mouse embryo fibroblast 3T3-L1 cells

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Abstract

The extracellular matrix (ECM) is a major biomechanical environment for all cells in vivo, and tightly controls wound healing and cancer progression. Type I collagen (Col I) is the most abundant component in ECM and plays an essential role for cell motility control and migration beyond structural support. Our previous results showed that Col I increased the length of primary cilia and the expression of primary cilia-associated proteins in 3T3-L1 cells. The Hippo/YAP pathway serves as a major integrator of cell surface-mediated signals and regulates key processes for the development and maintenance of tissue functions. In this study, we investigated the role of Hippo/YAP signaling in primary cilia growth of cells cultured on Col I-coated plate, as well as the potential link between primary cilia and migration. At 2-day post-confluence, YAP localization in the nucleus was dramatically increased when the cells were cultured on Col I-coated plate, accompanied by cilia growth. YAP inhibitor verteporfin repressed the growth of primary cilia as well as the expressions of ciliogenesis-associated proteins in confluent 3T3-L1 cells cultured on Col I-coated plate. Moreover, knockdown of either YAP or IFT88, one of the ciliogenesis-associated proteins, reversed the migration of confluent 3T3-L1 cells promoted by Col I-coating. In conclusion, activation of YAP pathway by Col I-coating of culture plate for confluent 3T3-L1 cells is positively associated with the primary cilia growth, which eventually results in promoted migration.

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Authors and Affiliations

  1. China-Japan Research Institute of Medical and Pharmaceutical Sciences, Wuya Colleage of Innovation, Shenyang Pharmaceutical University, Shenyang, 110016, China

    Qian Xu, Xiaoling Liu, Weiwei Liu, Toshihiko Hayashi & Takashi Ikejima

  2. Institute of Advanced Biomedical Engineering and Sciences, Tokyo Women’s Medical University, Tokyo, 162-8666, Japan

    Masayuki Yamato

  3. Nippi Research Institute of Biomatrix, Toride, Ibaraki, 302-0017, Japan

    Hitomi Fujisaki & Shunji Hattori

  4. Department of Medical Education & Primary Care, Kyoto Prefectural University of Medicine, Kajiicho 465, Kamikyo-ku, Kyoto City, Kyoto, 602-8566, Japan

    Shin-ichi Tashiro

  5. Department of Clinical and Pharmaceutical Sciences, Showa Pharmaceutical University, Tokyo, 194-8543, Japan

    Satoshi Onodera

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  1. Qian Xu
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  2. Xiaoling Liu
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Correspondence to Takashi Ikejima.

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Xu, Q., Liu, X., Liu, W. et al. Type I collagen-induced YAP nuclear expression promotes primary cilia growth and contributes to cell migration in confluent mouse embryo fibroblast 3T3-L1 cells. Mol Cell Biochem 450, 87–96 (2019). https://doi.org/10.1007/s11010-018-3375-z

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