Targeting ceramide synthase 6–dependent metastasis-prone phenotype in lung cancer cells
Project/Area Number |
18H02698
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Review Section |
Basic Section 50020:Tumor diagnostics and therapeutics-related
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Research Institution | Fujita Health University |
Principal Investigator |
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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)
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Project Period (FY) |
2018-04-01 – 2022-03-31
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Project Status |
Completed (Fiscal Year 2021)
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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)
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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.
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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。
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Report
(5 results)
Research Products
(33 results)
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[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
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Journal Title
Cancer Science
Volume: 未定
Issue: 7
Pages: 2770-2780
DOI
Related Report
Peer Reviewed / Open Access
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[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
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Journal Title
Cancer Sci.
Volume: 112
Issue: 4
Pages: 1614-1623
DOI
Related Report
Peer Reviewed / Open Access
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[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
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Journal Title
Cancer Science
Volume: in press
Related Report
Peer Reviewed / Open Access
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[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.
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Journal Title
Cancer Sci.
Volume: 112
Issue: 3
Pages: 1225-1234
DOI
Related Report
Peer Reviewed / Open Access
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[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
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Journal Title
Cancer Science
Volume: 111
Issue: 12
Pages: 4359-4370
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[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.
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Journal Title
J Cell Mol Med.
Volume: 24
Issue: 20
Pages: 11949-11959
DOI
Related Report
Peer Reviewed / Open Access
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[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
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Journal Title
EMBO J
Volume: 38
Issue: 17
Pages: 1-13
DOI
Related Report
Peer Reviewed / Open Access
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[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.
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Journal Title
Oncogene
Volume: -
Issue: 26
Pages: 5142-5157
DOI
Related Report
Peer Reviewed / Open Access
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[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.
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Journal Title
Biochem Biophys Rep.
Volume: 15
Pages: 69-75
DOI
Related Report
Peer Reviewed / Open Access
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[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
Invited
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[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
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