2021/12/06 更新

写真a

エサキ ノブトシ
江﨑 寛季
ESAKI Nobutoshi
所属
大学院医学系研究科 附属医学教育研究支援センター 先端領域支援部門 特任助教
職名
特任助教

学位 1

  1. 博士(医学) ( 2020年12月   名古屋大学 ) 

 

論文 6

  1. The Daple-CK1 epsilon complex regulates Dvl2 phosphorylation and canonical Wnt signaling

    Esaki Nobutoshi, Enomoto Atsushi, Takagishi Maki, Mizutani Yasuyuki, Iida Tadashi, Ushida Kaori, Shiraki Yukihiro, Mii Shinji, Takahashi Masahide

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   532 巻 ( 3 ) 頁: 406 - 413   2020年11月

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    記述言語:日本語   出版者・発行元:Biochemical and Biophysical Research Communications  

    The canonical Wnt signaling pathway plays a crucial role in embryonic development, tissue homeostasis and cancer progression. The binding of Wnt ligands to their cognate receptors, the Frizzled (Fzd) family of proteins, recruits Dishevelled segment polarity protein (Dvl) to the plasma membrane and induces its phosphorylation via casein kinase 1 (CK1), which leads to the activation of β-catenin. Previous studies showed that Dishevelled-associating protein with a high frequency of leucine residues (Daple) is an important component of the Wnt signaling pathway and essential for Dvl phosphorylation. However, the mechanism by which Daple promotes CK1-mediated phosphorylation of Dvl is not fully understood. In this study, we found that Daple overexpression induced CK1ε-mediated Dvl2 phosphorylation at threonine 224 (Thr224). A Daple mutant (Daple ΔGCV) that lacks a carboxyl-terminal motif to associate with Dvl, retained the ability to interact with CK1ε, but did not induce Dvl phosphorylation, suggesting the importance of the Daple/Dvl/CK1ε trimeric protein complex. We further found that Thr224 phosphorylation of Dvl was required for full activation of β-catenin transcriptional activity. Consistent with this, wild-type Daple promoted β-catenin transcriptional activity, following dissociation of β-catenin and axin. Finally, Wnt3a stimulation increased the membrane localization of Daple and its association with Dvl, and Daple knockdown attenuated Wnt3a-mediated β-catenin transcriptional activity. Collectively, these data suggested a essential role of spatial Daple localization in CK1ε-mediated activation of Dvl in the canonical Wnt signaling pathway.

    DOI: 10.1016/j.bbrc.2020.08.066

    Web of Science

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    PubMed

  2. Cytoplasmic Dynein Functions in Planar Polarization of Basal Bodies within Ciliated Cells

    Takagishi Maki, Esaki Nobutoshi, Takahashi Kunihiko, Takahashi Masahide

    ISCIENCE   23 巻 ( 6 ) 頁: 101213   2020年6月

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    記述言語:日本語   出版者・発行元:iScience  

    Despite common consensus about the importance of planar cell polarity (PCP) proteins in tissue orientation, little is known about the mechanisms used by PCP proteins to promote planar polarization of cytoskeletons within individual cells. One PCP protein Fzd6 asymmetrically localizes to the apical cell membrane of multi-ciliated ependymal cells lining the lateral ventricular (LV) wall on the side that contacts cerebrospinal fluid flow. Individual ependymal cells have planar polarized microtubules that connect ciliary basal bodies (BBs) with the cell cortex of the Fzd side to coordinate cilia orientation. Here, we report that cytoplasmic dynein is anchored to the cell cortex of the Fzd side via an adapter protein Daple that regulates microtubule dynamics. Asymmetric localization of cortical dynein generates a pulling force on dynamic microtubules connected to BBs, which in turn orients BBs toward the Fzd side. This is required for coordinated cilia orientation on the LV wall.

    DOI: 10.1016/j.isci.2020.101213

    Web of Science

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    PubMed

  3. Cancer-associated fibroblasts that restrain cancer progression: Hypotheses and perspectives

    Miyai Yuki, Esaki Nobutoshi, Takahashi Masahide, Enomoto Atsushi

    CANCER SCIENCE   111 巻 ( 4 ) 頁: 1047 - 1057   2020年4月

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    記述言語:日本語   出版者・発行元:Cancer Science  

    The roles of cancer-associated fibroblasts (CAF) in the progression of various types of cancers are well established. CAF promote cancer progression through pleiotropic mechanisms, including the secretion of soluble factors and extracellular matrix, physical interactions with cancer cells, and the regulation of angiogenesis, immunity and metabolism. Their contribution to therapeutic resistance is also well appreciated. Therefore, CAF have been considered as a therapeutic target in cancer. However, recent studies in autochthonous pancreatic cancer models suggest that specific subset(s) of CAF exhibit cancer-restraining roles, indicating that CAF are functionally and molecularly heterogeneous, which is supported by recent single-cell transcriptome analyses. While cancer-promoting CAF (pCAF) have been extensively studied, the nature and specific marker(s) of cancer-restraining CAF (rCAF) have remained uncharacterized. Interestingly, a recent study provided insight into the nature of rCAF and suggested that they may share molecular properties with pancreatic stellate cells (PSC) and mesenchymal stem/stromal cells (MSC). Complicating this finding is that PSC and MSC have been shown to promote the formation of a tumor-permissive and tumor-promoting environment in xenograft tumor models. However, these cells undergo significant transcriptional and epigenetic changes during ex vivo culture, which confounds the interpretation of experimental results based on the use of cultured cells. In this short review, we describe recent studies and hypotheses on the identity of rCAF and discuss their analogy to fibroblasts that suppress fibrosis in fibrotic diseases. Finally, we discuss how these findings can be exploited to develop novel anticancer therapies in the future.

    DOI: 10.1111/cas.14346

    Web of Science

    Scopus

    PubMed

  4. Meflin-Positive Cancer-Associated Fibroblasts Inhibit Pancreatic Carcinogenesis 査読有り

    Yasuyuki Mizutani, Hiroki Kobayashi, Tadashi Iida, Naoya Asai, Atsushi Masamune, Akitoshi Hara, Nobutoshi Esaki, Kaori Ushida, Shinji Mii, Yukihiro Shiraki, Kenju Ando, Liang Weng, Seiichiro Ishihara, Suzanne M. Ponik, Matthew W. Conklin, Hisashi Haga, Arata Nagasaka, Takaki Miyata, Makoto Matsuyama, Tomoe Kobayashi, Tsutomu Fujii, Suguru Yamada, Junpei Yamaguchi, Tongtong Wang, Susan L. Woods, Daniel Worthley, Teppei Shimamura, Mitsuhiro Fujishiro, Yoshiki Hirooka, Atsushi Enomoto, Masahide Takahashi

    Cancer Research   79 巻 ( 20 ) 頁: 5367 - 5381   2019年10月

  5. Girdin/GIV regulates collective cancer cell migration by controlling cell adhesion and cytoskeletal organization 査読有り

    Xiaoze Wang, Atsushi Enomoto, Liang Weng, Yasuyuki Mizutani, Shaniya Abudureyimu, Nobutoshi Esaki, Yuta Tsuyuki, Chen Chen, Shinji Mii, Naoya Asai, Hisashi Haga, Sumire Ishida, Kenji Yokota, Masashi Akiyama, Masahide Takahashi

    Cancer Science   109 巻 ( 11 ) 頁: 3643 - 3656   2018年9月

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  6. ASC amino acid transporter 2, defined by enzyme-mediated activation of radical sources, enhances malignancy of GD2-positive small-cell lung cancer 査読有り

    Nobutoshi Esaki, Yuki Ohkawa, Noboru Hashimoto, Yuhsuke Tsuda, Yuhsuke Ohmi, Robiul H. Bhuiyan, Norihiro Kotani, Koichi Honke, Atsushi Enomoto, Masahide Takahashi, Keiko Furukawa, Koichi Furukawa

    Cancer Science   109 巻 ( 1 ) 頁: 141 - 153   2017年11月

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