Molecular Oncology

mizutani yasuyoshi

  (水谷 泰嘉)

Profile Information

Affiliation
Fujita Health University
Degree
博士(医学)

J-GLOBAL ID
201501019923417825
researchmap Member ID
7000012693

Committee Memberships

 2

Papers

 27
  • Atsuko Niimi, Siripan Limsirichaikul, Keiko Kano, Yasuyoshi Mizutani, Toshiyuki Takeuchi, Patinya Sawangsri, Dat Quoc Tran, Yoshiyuki Kawamoto, Motoshi Suzuki
    Cancers, 15(10) 2781-2781, May 16, 2023  Peer-reviewed
    CERS6 is associated with metastasis and poor prognosis in non-small cell lung cancer (NSCLC) patients through d18:1/C16:0 ceramide (C16 ceramide)-mediated cell migration, though the detailed mechanism has not been elucidated. In the present study, examinations including co-immunoprecipitation, liquid chromatography, and tandem mass spectrometry analysis were performed to identify a novel binding partner of CERS6. Among the examined candidates, LASP1 was a top-ranked binding partner, with the LIM domain possibly required for direct interaction. In accord with those findings, CERS6 and LASP1 were found to co-localize on lamellipodia in several lung cancer cell lines. Furthermore, silencing of CERS6 and/or LASP1 significantly suppressed cell migration and lamellipodia formation, whereas ectopic addition of C16 ceramide partially rescued those phenotypes. Both LASP1 and CERS6 showed co-immunoprecipitation with actin, with those interactions markedly reduced when the LASP1–CERS6 complex was abolished. Based on these findings, it is proposed that LASP1–CERS6 interaction promotes cancer cell migration.
  • Yasuyoshi Mizutani, Kazuya Shiogama, Ken-Ichi Inada, Toshiyuki Takeuchi, Atsuko Niimi, Motoshi Suzuki, Yutaka Tsutsumi
    Acta histochemica et cytochemica, 55(5) 129-148, Oct 28, 2022  Peer-reviewed
    The enzyme-labeled antigen method is an immunohistochemical technique detecting plasma cells producing specific antibodies in tissue sections. The probe is an antigen labeled with an enzyme or biotin. This immunohistochemical technique is appliable to frozen sections of paraformaldehyde (PFA)-fixed tissues, but it has been difficult to apply it to formalin-fixed, paraffin-embedded (FFPE) sections. In the current study, factors inactivating the antibody reactivity during the process of preparing FFPE sections were investigated. Lymph nodes of rats immunized with horseradish peroxidase (HRP) or a mixture of keyhole limpet hemocyanin/ovalbumin/bovine serum albumin were employed as experimental models. Plasma cells producing specific antibodies, visualized with HRP (as an antigen with enzymatic activity) or biotinylated proteins in 4% PFA-fixed frozen sections, significantly decreased in unbuffered 10% formalin-fixed frozen sections. The positive cells were further decreased by paraffin embedding following formalin fixation. In paraffin-embedded sections fixed in precipitating fixatives such as ethanol and acetone and those prepared with the AMeX method, the antigen-binding reactivity of antibodies was preserved. Fixation in periodate-lysine-paraformaldehyde and Zamboni solution also kept the antigen-binding reactivity in paraffin to some extent. In conclusion, formalin fixation and paraffin embedding were major causes inactivating antibodies. Precipitating fixatives could retain the antigen-binding reactivity of antibodies in paraffin-embedded sections.
  • Keiko Tamiya-Koizumi, Yurika Otoki, Kiyotaka Nakagawa, Reiji Kannagi, Naoki Mizutani, Motoshi Suzuki, Mamoru Kyogashima, Soichiro Iwaki, Mineyoshi Aoyama, Takashi Murate, Kazuyuki Kitatani, Takahisa Kuga, Yasuyoshi Mizutani, Akira Tokumura
    Biochemical and Biophysical Research Communications, Apr, 2022  Peer-reviewed
  • Hanxiao Shi, Atsuko Niimi, Toshiyuki Takeuchi, Kazuya Shiogama, Yasuyoshi Mizutani, Taisuke Kajino, Kenichi Inada, Tetsunari Hase, Takahiro Hatta, Hirofumi Shibata, Takayuki Fukui, Toyofumi Fengshi Chen-Yoshikawa, Kazuki Nagano, Takashi Murate, Yoshiyuki Kawamoto, Shuta Tomida, Takashi Takahashi, Motoshi Suzuki
    Cancer science, 112(7) 2770-2780, Jul, 2021  Peer-reviewed
    Ceramide synthase 6 (CERS6) promotes lung cancer metastasis by stimulating cancer cell migration. To examine the underlying mechanisms, we performed luciferase analysis of the CERS6 promoter region and identified the Y-box as a cis-acting element. As a parallel analysis of database records for 149 non-small-cell lung cancer (NSCLC) cancer patients, we screened for trans-acting factors with an expression level showing a correlation with CERS6 expression. Among the candidates noted, silencing of either CCAAT enhancer-binding protein γ (CEBPγ) or Y-box binding protein 1 (YBX1) reduced the CERS6 expression level. Following knockdown, CEBPγ and YBX1 were found to be independently associated with reductions in ceramide-dependent lamellipodia formation as well as migration activity, while only CEBPγ may have induced CERS6 expression through specific binding to the Y-box. The mRNA expression levels of CERS6, CEBPγ, and YBX1 were positively correlated with adenocarcinoma invasiveness. YBX1 expression was observed in all 20 examined clinical lung cancer specimens, while 6 of those showed a staining pattern similar to that of CERS6. The present findings suggest promotion of lung cancer migration by possible involvement of the transcription factors CEBPγ and YBX1.
  • Motoshi Suzuki, Ke Cao, Seiichi Kato, Naoki Mizutani, Kouji Tanaka, Chinatsu Arima, Mei Chee Tai, Norie Nakatani, Kiyoshi Yanagisawa, Toshiyuki Takeuchi, Hanxiao Shi, Yasuyoshi Mizutani, Atsuko Niimi, Tetsuo Taniguchi, Takayuki Fukui, Kohei Yokoi, Keiko Wakahara, Yoshinori Hasegawa, Yukiko Mizutani, Soichiro Iwaki, Satoshi Fujii, Akira Satou, Keiko Tamiya-Koizumi, Takashi Murate, Mamoru Kyogashima, Shuta Tomida, Takashi Takahashi
    Journal of cellular and molecular medicine, 24(20) 11949-11959, Oct, 2020  Peer-reviewed
    Sphingolipids constitute a class of bio-reactive molecules that transmit signals and exhibit a variety of physical properties in various cell types, though their functions in cancer pathogenesis have yet to be elucidated. Analyses of gene expression profiles of clinical specimens and a panel of cell lines revealed that the ceramide synthase gene CERS6 was overexpressed in non-small-cell lung cancer (NSCLC) tissues, while elevated expression was shown to be associated with poor prognosis and lymph node metastasis. NSCLC profile and in vitro luciferase analysis results suggested that CERS6 overexpression is promoted, at least in part, by reduced miR-101 expression. Under a reduced CERS6 expression condition, the ceramide profile became altered, which was determined to be associated with decreased cell migration and invasion activities in vitro. Furthermore, CERS6 knockdown suppressed RAC1-positive lamellipodia/ruffling formation and attenuated lung metastasis efficiency in mice, while forced expression of CERS6 resulted in an opposite phenotype in examined cell lines. Based on these findings, we consider that ceramide synthesis by CERS6 has important roles in lung cancer migration and metastasis.

Misc.

 50

Books and Other Publications

 3

Presentations

 80

Teaching Experience

 3

Research Projects

 9

Other

 2
  • 特になし
  • ①酵素抗原法(標識抗原をプローブとすることで、組織内の特異抗体の標的抗原を同定して、その抗体を産生する形質細胞の局在を可視化する技術。Mizutani Y et al. Acta Histochemica et Cytochemica. Volume 49 (1), 7-19, 2016.) *本研究シーズに関する産学共同研究の問い合わせは藤田医科大学産学連携推進センター(fuji-san@fujita-hu.ac.jp)まで

教育内容・方法の工夫(授業評価等を含む)

 2
  • 件名(英語)
    看護専門学校・病理学総論
    開始年月日(英語)
    2010
    終了年月日(英語)
    2013
    概要(英語)
    看護専門学校において、病理学総論(30時間)を担当した。
  • 件名(英語)
    医学部・病態病理実習、病理学実習
    開始年月日(英語)
    2009
    終了年月日(英語)
    2013
    概要(英語)
    病態病理実習(16時間)および病理学実習(16時間)を分担した。