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Targeting ceramide synthase 6–dependent metastasis-prone phenotype in lung cancer cells

Research Project

Project/Area Number 18H02698
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 50020:Tumor diagnostics and therapeutics-related
Research InstitutionFujita Health University

Principal Investigator

Suzuki Motoshi  藤田医科大学, 医学部, 教授 (80236017)

Co-Investigator(Kenkyū-buntansha) 水谷 泰嘉  藤田医科大学, 医学部, 助教 (10546229)
竹内 俊幸  藤田医科大学, 医学部, 助教 (20538483)
安藤 隆幸  静岡県環境衛生科学研究所, 医薬食品部, 主査 (40402226)
新美 敦子  藤田医科大学, 医学部, 准教授 (50508984)
村手 隆  中部大学, 生命健康科学部, 教授 (30239537)
Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2021: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2020: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2019: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2018: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Keywords肺癌 / CERS6 / 転移 / セラミド / 細胞遊走 / スフィンゴ脂質 / 創薬 / 細胞骨格 / アクチン / 転写因子 / 肺がん
Outline of Final Research Achievements

CERS6 is required for cell migration, which is a major process of cancer metastasis. In this study, we identified CERS6-binding proteins, and showed that one of them has the CERS6 recruiting function to lamellipodia. We also showed that CEBPγ and YBX1 induced CERS6 expression and promoted cancer cell migration through ceramide-dependent lamellipodia formation. Furthermore, we conducted structural optimization research to develop a metastasis-preventive drug by screening small molecule compounds and chemical synthesis.

Academic Significance and Societal Importance of the Research Achievements

近年、がん生存シグナル経路、免疫チェックポイント等を標的とした治療が可能となり、ステージの進んだ患者においても、一部で良好な治療結果が期待できるようになっている。しかし、残念ながらすべての患者がその恩恵を受けられるわけではない。これに対して各種解決努力が続けられる一方で、根本的に新たな発想と作用機序に基づく治療法開発が期待されている。申請者らは、近年がん特異的発現し、がん転移亢進をするCERS6を同定した。しかし、CERS6を介するがん転移経路の詳細は多くが未解明である。また、この経路を標的とする分子標的薬もない。本研究はこれら背景の下、がん転移機序解明と眼底抑制剤開発を目的としたものである。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (33 results)

All 2022 2021 2020 2019 2018 Other

All Journal Article (15 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 15 results,  Open Access: 13 results) Presentation (14 results) (of which Int'l Joint Research: 1 results,  Invited: 2 results) Book (2 results) Remarks (1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Cellular concentrations of plasmalogen species containing a polyunsaturated fatty acid significantly increase under hypoxia in human colorectal cancer, Caco2 cells2022

    • Author(s)
      Tamiya-Koizumi Keiko、Otoki Yurika、Nakagawa Kiyotaka、Kannagi Reiji、Mizutani Naoki、Suzuki Motoshi、Kyogashima Mamoru、Iwaki Soichiro、Aoyama Mineyoshi、Murate Takashi、Kitatani Kazuyuki、Kuga Takahisa、Mizutani Yasuyoshi、Tokumura Akira
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 611 Pages: 1-7

    • DOI

      10.1016/j.bbrc.2022.04.061

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] CEBPγ facilitates lamellipodia formation and cancer cell migration through CERS6 upregulation2021

    • Author(s)
      Hanxiao Sh, 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
    • Journal Title

      Cancer Science

      Volume: 未定 Issue: 7 Pages: 2770-2780

    • DOI

      10.1111/cas.14928

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Conditional Ror1 knockout reveals crucial involvement in lung adenocarcinoma development and identifies novel HIF-1α regulator2021

    • Author(s)
      Hisanori Isomura, Ayumu Taguchi, Taisuke Kajino, Naoya Asai, Masahiro Nakatochi, Seiichi Kato, Keiko Suzuki, Kiyoshi Yanagisawa, Motoshi Suzuki, Teruaki Fujishita, Tomoya Yamaguchi, Masahide Takahashi, Takashi Takahashi
    • Journal Title

      Cancer Sci.

      Volume: 112 Issue: 4 Pages: 1614-1623

    • DOI

      10.1111/cas.14825

    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Increased chemosensitivity via BRCA2-independent DNA damage in DSS1- and PCID2-depleted breast carcinomas2021

    • Author(s)
      Gondo Naomi、Sakai Yasuhiro、Zhang Zhenhuan、Hato Yukari、Kuzushima Kiyotaka、Phimsen Suchada、Kawashima Yoshiaki、Kuroda Makoto、Suzuki Motoshi、Okada Seiji、Iwata Hiroji、Toyama Tatsuya、Rezano Andri、Kuwahara Kazuhiko
    • Journal Title

      Laboratory Investigation

      Volume: 101 Issue: 8 Pages: 1048-1059

    • DOI

      10.1038/s41374-021-00613-6

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Adipsin-Dependent Secretion of Hepatocyte Growth Factor Regulates the Adipocyte-Cancer Stem Cell Interaction2021

    • Author(s)
      Mizuno Masahiro、Khaledian Behnoush、Maeda Masao、Hayashi Takanori、Mizuno Seiya、Munetsuna Eiji、Watanabe Takashi、Kono Seishi、Okada Seiji、Suzuki Motoshi、Takao Shintaro、Minami Hironobu、Asai Naoya、Sugiyama Fumihiro、Takahashi Satoru、Shimono Yohei
    • Journal Title

      Cancers

      Volume: 13 Issue: 16 Pages: 4238-4238

    • DOI

      10.3390/cancers13164238

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] CEBPgamma facilitates lamellipodia formation and cancer cell migration through CERS6 upregulation2021

    • Author(s)
      Shi H, Niimi A, Takeuchi T, Shiogama K, Mizutani Y, Kajino T, Inada K, Hase T, Hatta T, Shibata H, Fukui T, Chen-Yoshikawa T-F, Nagano K, Murate T, Kawamoto Y, Tomida S, Takahashi T, Suzuki, M
    • Journal Title

      Cancer Science

      Volume: in press

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Inhibition of HSP90 destabilizes receptor tyrosine kinase ROR1 in lung adenocarcinoma.2021

    • Author(s)
      Khaledian B, Taguchi A, Shin-ya, K, Kondo-Ida L, Kagaya N, Suzuki M, Kajino T, Yamaguchi T, Shimada Y, Takahashi T.
    • Journal Title

      Cancer Sci.

      Volume: 112 Issue: 3 Pages: 1225-1234

    • DOI

      10.1111/cas.14786

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Combined α-methylacyl-CoA racemase inhibition and docetaxel treatment reduce cell proliferation and decrease expression of heat shock protein 27 in androgen receptor-variant-7?positive prostate cancer cells2021

    • Author(s)
      Yoshizawa Atsuhiko、Takahara Kiyoshi、Saruta Masanobu、Zennami Kenji、Nukaya Takuhisa、Fukaya Kosuke、Ichino Manabu、Fukami Naohiko、Niimi Atsuko、Sasaki Hitomi、Kusaka Mamoru、Suzuki Motoshi、Sumitomo Makoto、Shiroki Ryoichi
    • Journal Title

      Prostate International

      Volume: 9 Issue: 1 Pages: 18-24

    • DOI

      10.1016/j.prnil.2020.07.001

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Upregulation of S100A10 in metastasized breast cancer stem cells2020

    • Author(s)
      Yanagi Hisano、Watanabe Takashi、Nishimura Tatsunori、Hayashi Takanori、Kono Seishi、Tsuchida Hitomi、Hirata Munetsugu、Kijima Yuko、Takao Shintaro、Okada Seiji、Suzuki Motoshi、Imaizumi Kazuyoshi、Kawada Kenji、Minami Hironobu、Gotoh Noriko、Shimono Yohei
    • Journal Title

      Cancer Science

      Volume: 111 Issue: 12 Pages: 4359-4370

    • DOI

      10.1111/cas.14659

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] CERS6 required for cell migration and metastasis in lung cancer.2020

    • Author(s)
      Suzuki M, Cao K, Kato S, Mizutani N, Tanaka K, Arima C, Tai MC, Nakatani N, Yanagisawa K, Takeuchi T, Shi H, Mizutani Y, Niimi A, Taniguchi T, Fukui T, Yokoi K, Wakahara K, Hasegawa Y, Mizutani Y, Iwaki S, Fujii S, Satou A, Tamiya-Koizumi K, Murate T, Kyogashima M, Tomida S, Takahashi T.
    • Journal Title

      J Cell Mol Med.

      Volume: 24 Issue: 20 Pages: 11949-11959

    • DOI

      10.1111/jcmm.15817

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A Novel Cytological Model of B-Cell/Macrophage Biphenotypic Cell Hodgkin Lymphoma in Ganp-Transgenic Mice2020

    • Author(s)
      Sakai、Rezano、Okada、Ohtsuki、Kawashima、Tsukamoto、Suzuki、Kohara、Takeya、Sakaguchi、Kuwahara
    • Journal Title

      Cancers

      Volume: 12 Issue: 1 Pages: 204-204

    • DOI

      10.3390/cancers12010204

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Involvement of MCL1, c-myc, and cyclin D2 protein degradation in ponatinib-induced cytotoxicity against T315I(+) Ph+leukemia cells2020

    • Author(s)
      Inoue Chisato、Sobue Sayaka、Kawamoto Yoshiyuki、Nishizawa Yuji、Ichihara Masatoshi、Abe Akihiro、Hayakawa Fumihiko、Suzuki Motoshi、Nozawa Yoshinori、Murate Takahsi
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 525 Issue: 4 Pages: 1074-1080

    • DOI

      10.1016/j.bbrc.2020.02.165

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Divergent lncRNA MYMLR regulates MYC by eliciting DNA looping and promoter-enhancer interaction2019

    • Author(s)
      Kajino T, Shimamura T, Gong S, Yanagisawa K, Ida L, Nakatochi M, Griesing S, Shimada Y, Kano K, Suzuki M, Miyano S
    • Journal Title

      EMBO J

      Volume: 38 Issue: 17 Pages: 1-13

    • DOI

      10.15252/embj.201798441

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] ROR1-CAVIN3 interaction required for caveolae-dependent endocytosis and pro-survival signaling in lung adenocarcinoma2019

    • Author(s)
      Yamaguchi T, Hayashi M, Ida L, Yamamoto M, Lu C, Kajino T, Cheng J, Nakatochi M, Isomura H, Yamazaki M, Suzuki M, Fujimoto T, Takahashi T.
    • Journal Title

      Oncogene

      Volume: - Issue: 26 Pages: 5142-5157

    • DOI

      10.1038/s41388-019-0785-7

    • Related Report
      2019 Annual Research Report 2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] BCL2 inhibitor ABT-199 and JNK inhibitor SP600125 exhibit synergistic cytotoxicity against imatinib-resistant Ph+ ALL cells.2018

    • Author(s)
      Inoue C, Sobue S, Aoyama Y, Mizutani N, Kawamoto Y, Nishizawa Y, Ichihara M, Abe A, Hayakawa F, Suzuki M, Nozawa Y, Murate T.
    • Journal Title

      Biochem Biophys Rep.

      Volume: 15 Pages: 69-75

    • DOI

      10.1016/j.bbrep.2018.07.001

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] CERS6 and CEBPg required for cell migration and metastasis through an alteration in the ceramide metabolic profile.2021

    • Author(s)
      Hanxiao Shi, Toshiyuki Takeuchi, Atsuko Niimi, Yasuyoshi Mizutani, Taisuke Kajino, Shuta Tomida, Takashi Takahashi, Motoshi Suzuki
    • Organizer
      第80回日本癌学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Roles of gamma-glutamylcyclotransferase in the regulation of CSC properties and metastatic abilities in breast cancer.2021

    • Author(s)
      Takanori Hayashi, Masao Maeda, Motoshi Suzuki, Naoya Asai, Yohei Shimono
    • Organizer
      第80回日本癌学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] POLD4 pathway is required for repair of CDDP-induced DNA damage.2021

    • Author(s)
      Atsuko Niimi, Yasuyoshi Mizutani, Toshiyuki Takeuchi, Motoshi Suzuki
    • Organizer
      第80回日本癌学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Adipocytes enhance cancer stem cell-like properties in ovarian cancers through MCP1.2021

    • Author(s)
      Manaka Yano, Masao Maeda, Eiji Nishio, Shiori Takusagawa, Takanori Hayashi, Motoshi Suzuki, Naoya Asai, Takuma Fujii, Hideyuki Saya, Yohei Shimono
    • Organizer
      第80回日本癌学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Application of organoids to breast cancer research2021

    • Author(s)
      Yohei Shimono, Tatsunori Nishimura, Seishi Kono, Naoki Shibuya, Takanori Hayashi, Hisano Yanagi, Takashi Watanabe, Masao Maeda, Yoshihiro Kakeji, Kenji Kawada, Naoya Asai, Shintaro Takao, Hironobu Minami, Yuko Kijima, Motoshi Suzuki, Noriko Gotoh
    • Organizer
      第80回日本癌学会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Upregulation of S100A10 in metastasized breast cancer stem cells2020

    • Author(s)
      Hisano Yanagi, Takashi Watanabe, Tatsunori Nishimura, Takanori Hayashi, Seiji Okada, Motoshi Suzuki, Hironobu Minami, Akira Suzuki, Kenji Kawada, Noriko Gotoh, Yohei Shimono
    • Organizer
      日本癌学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Gamma-glutamylcyclotransferase as a novel regulator of cancer stem cell properties in breast cancers2020

    • Author(s)
      Takanori Hayashi, Masao Maeda, Seiji Okada, Motoshi Suzuki, Yohei Shimono
    • Organizer
      日本癌学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] A suppressor role of POLD4, the smallest subunit of DNA polymerase d complex, in lung cancer2020

    • Author(s)
      Atsuko Niimi, Yasuyoshi Mizutani, Toshiyuki Takeuchi, Motoshi Suzuki
    • Organizer
      日本癌学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] CEBPg and YBX1 regulate lung cancer metastasis via CERS6 expression and lamellipodia formation2020

    • Author(s)
      47.CEBPg and YBX1 regulate lung cancer metastasis via CERS6 expression and lamellipodia formation
    • Organizer
      日本癌学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] DNAポリメラーゼδ複合体サブユニットPOLD4の肺がん発生における役割解析2019

    • Author(s)
      新美敦子、岩瀬咲良、竹内俊幸、水谷泰嘉、鈴木元
    • Organizer
      第42回日本分子生物学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 病変組織内の特異的抗体産生細胞を可視化する「酵素抗原法」の技術開発2019

    • Author(s)
      水谷泰嘉、塩竈和也、竹内俊幸、新美敦子、石含笑、稲田健一、鈴木元
    • Organizer
      第60回日本組織細胞化学会総会・学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] nanoLC-MS を用いたインタクトタンパク質の翻訳後修飾解析2019

    • Author(s)
      加納圭子,新美敦子, 鈴木元, 小林宏資, 和田啓男, 桑田啓子
    • Organizer
      第70回日本電気泳動学会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] DNA polymerase delta and cancer.2018

    • Author(s)
      Suzuki M
    • Organizer
      Fidelity, Mutations in Cancer Symposium
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] A metastasis protein CERS6 is transcriptionally regulated by miR-101 and YB-1.2018

    • Author(s)
      Hanxiao Shi, Toshiyuki Takeuchi, Atsuko Niimi, Yasuyoshi Mizutani, Takashi Murate, Takashi Suzuki, Motoshi Suzuki
    • Organizer
      第76回日本癌学会総会
    • Related Report
      2018 Annual Research Report
  • [Book] がん生物学イラストレイテッド 第2版 (p185-192)2019

    • Author(s)
      渋谷 正史:湯浅 保仁 ( 分担執筆: 水谷泰嘉、鈴木元)
    • Total Pages
      504
    • Publisher
      羊土社
    • ISBN
      9784758120968
    • Related Report
      2019 Annual Research Report
  • [Book] がん生物学イラストレーテッド(がんとmicroRNAセクション)2019

    • Author(s)
      水谷泰嘉、鈴木元
    • Publisher
      羊土社
    • Related Report
      2018 Annual Research Report
  • [Remarks] ようこそ 分子腫瘍学講座のHPへ

    • URL

      http://info.fujita-hu.ac.jp/~motosuzu/index.html

    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
  • [Patent(Industrial Property Rights)] がん転移抑制剤2019

    • Inventor(s)
      鈴木元、竹内俊幸、高橋隆、磯村久徳、小泉惠子、安藤隆幸
    • Industrial Property Rights Holder
      学校法人藤田学園
    • Industrial Property Rights Type
      特許
    • Filing Date
      2019
    • Related Report
      2018 Annual Research Report

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Published: 2018-04-23   Modified: 2023-01-30  

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