Regulation of cellular metabolism and functions mediated by amino acid transporters and the mechanisms of action of their inhibitors
Project/Area Number |
15H04685
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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 |
Research Field |
General pharmacology
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Research Institution | Osaka University |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
永森 收志 大阪大学, 医学系研究科, 准教授 (90467572)
大垣 隆一 大阪大学, 医学系研究科, 助教 (20467525)
奥田 傑 大阪大学, 医学系研究科, 助教 (50511846)
中込 咲綾 大阪大学, 医学(系)研究科(研究院), 特任助教(常勤) (60423894)
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Project Period (FY) |
2015-04-01 – 2018-03-31
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Project Status |
Completed (Fiscal Year 2017)
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Budget Amount *help |
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2017: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2016: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2015: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
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Keywords | トランスポーター / 受容体 / シグナル伝達系 / 細胞代謝制御 / 抗腫瘍薬 / がん / アミノ酸トランスポーター / リン酸化プロテオミクス / 腫瘍血管新生 / チャネル / 輸送系 / シグナル情報伝達系 / 輸送体介在シグナル / 代謝制御・細胞機能制御 |
Outline of Final Research Achievements |
Amino acid transporter LAT1 (L-type amino acid transporter 1) is highly upregulated in various types of cancer. LAT1 is known to supply cancer cells with most of the essential amino acids, thereby supporting the rapid cell growth and proliferation. By using newly developed LAT1-selective inhibitor, we tried to understand the functions of amino acids as signaling molecules, and to reveal the cellular metabolisms and other cellular functions regulated by amino acids transported by LAT1, especially leucine. Phosphoproteomics analysis revealed amino acid signaling in the downstream of LAT1. We also demonstrated relationships between LAT1 with tumor angiogenesis and metastasis. This research revealed novel functional aspects of the amino acid transporter and amino acid signaling. The results obtained also contributed to the comprehensive understanding of the mechanisms of action of LAT1 inhibitors as a novel class of anti-cancer agents.
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Report
(4 results)
Research Products
(124 results)
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[Journal Article] Relationship between LAT1 expression and resistance to chemotherapy in pancreatic ductal adenocarcinoma.2018
Author(s)
Altan B, Kaira K, Watanabe A, Kubo N, Bao P, Dolgormaa G, Bilguun EO, Araki K, Kanai Y, Yokobori T, Oyama T, Nishiyama M, Kuwano H, Shirabe K
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Journal Title
Cancer chemotherapy and pharmacology
Volume: 81
Pages: 141-153
DOI
Related Report
Peer Reviewed
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[Journal Article] Negative regulation of amino acid signaling by MAPK-regulated 4F2hc/Girdin complex.2018
Author(s)
Liang Weng , Yi-Peng Han, Atsushi Enomoto, Yasuyuki Kitaura, Shushi Nagamori, Yoshikatsu Kanai, Naoya Asai, Jian An, Maki Takagishi, Masato Asai, Shinji Mii, Takashi Masuko, Yoshiharu Shimomura, Masahide Takahashi.
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Journal Title
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Clinical Significance and Phenotype of MTA1 Expression in Esophageal Squamous Cell Carcinoma.2017
Author(s)
Honjo H, Toh Y, Sohda M, Suzuki S, Kaira K, Kanai Y, Nagamori S, Oyama T, Yokobori T, Miyazaki T, Kuwano H
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Journal Title
Anticancer Research
Volume: 37
Pages: 4147-4155
DOI
Related Report
Peer Reviewed
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[Journal Article] Slc3a2 Mediates Branched-Chain Amino-Acid-Dependent Maintenance of Regulatory T Cells2017
Author(s)
Ikeda K, Kinoshita M, Kayama H, Nagamori S, Kongpracha P, Umemoto E, Okumura R, Kurakawa T, Murakami M, Mikami N, Shintani Y, Ueno S, Andou A, Ito M, Tsumura H, Yasutomo K, Ozono K, Takashima S, Sakaguchi S, Kanai Y, Takeda K.
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Journal Title
Cell reports
Volume: 21
Pages: 1824-1838
DOI
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Peer Reviewed / Open Access
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[Journal Article] 18F-FBPA as a tumor-specific probe of L-type amino acid transporter 1 (LAT1): a comparison study with 18F-FDG and 11C-Methionine PET.2017
Author(s)
Watabe T, Ikeda H, Nagamori S, Wiriyasermkul P, Tanaka Y, Naka S, Kanai Y, Hagiwara K, Aoki M, Shimosegawa E, Kanai Y, Hatazawa J.
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Journal Title
European Journal of Nuclear Medicine and Molecular Imaging
Volume: 44
Pages: 321-331
DOI
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Peer Reviewed
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[Journal Article] Increased Dynamics of Tricarboxylic Acid Cycle and Glutamate Synthesis in Obese Adipose Tissue: In vivo Metabolic Turnover Analysis.2017
Author(s)
Nagao H, Nishizawa H, Bamba T, Nakayama Y, Isozumi N, Nagamori S, Kanai Y, Tanaka Y, Kita S, Fukuda S, Funahashi T, Maeda N, Fukusaki E, Shimomura I.
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Journal Title
J Biol Chem.
Volume: 292
Pages: 4469-4483
DOI
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Peer Reviewed / Open Access
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[Journal Article] Argininosuccinate Synthase 1-Deficiency Enhances the Cell Sensitivity to Arginine through Decreased DEPTOR Expression in Endometrial Cancer2017
Author(s)
Ohshima K, Nojima S, Tahara S, Kurashige M, Hori Y, Hagiwara K, Okuzaki D, Oki S, Wada N, Ikeda JI, Kanai Y, Morii E.
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Journal Title
Sci Rep.
Volume: 7
Pages: 45504-45504
DOI
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Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Core-fucosylation plays a pivotal role in hepatitis B pseudo virus infection: a possible implication for HBV glycotherapy2016
Author(s)
Takamatsu S, Shimomura M, Kamada Y, Maeda H, Sobajima T, Hikita H, Iijima M, Okamoto Y, Misaki R, Fujiyama K, Nagamori S, Kanai Y, Takehara T, Ueda K, Kuroda S, Miyoshi E.
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Journal Title
Glycobiology
Volume: 26
Pages: 1180-1189
DOI
Related Report
Peer Reviewed
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[Journal Article] Efficacy of LAT1 inhibition as a therapeutic target in esophageal squamous cell carcinoma2016
Author(s)
Ohshima Y, Kaira K, Yamaguchi A, Oriuchi N, Tominaga H, Nagamori S, Kanai Y, Yokobori T, Miyazaki T, Asao T, Tsushima Y, Kuwano H, Ishioka NS.
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Journal Title
Cancer Science
Volume: 107
Pages: 1499-1505
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Expression of a human NPT1/SLC17A1 missense variant which increases urate export.2016
Author(s)
Sakiyama M, Matsuo H, Nagamori S, Ling W, Kawamura Y, Nakayama A, Higashino T, Chiba T, Ichida K, Kanai Y, Shinomiya N.
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Journal Title
Nucleosides Nucleotides Nucleic Acids.
Volume: 35
Pages: 536-542
Related Report
Peer Reviewed
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[Journal Article] Impaired Amino Acid Transport at the Blood Brain Barrier Is a Cause of Autism Spectrum Disorder.2016
Author(s)
Tarlungeanu DC, Deliu E, Dotter CP, Kara M, Janiesch PC, Scalise M, Galluccio M, Tesulov M, Morelli E, Sonmez FM, Bilguvar K, Ohgaki R, Kanai Y, Johansen A, Esharif S, Ben-Omran T, Topcu M, Schlessinger A, Indiveri C, Duncan KE, Caglayan AO, Gunel M, Gleeson JG, Novarino G.
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Journal Title
Cell.
Volume: 167
Pages: 1481-1494
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Novel cystine transporter in renal proximal tubule identified as a missing partner of cystinuria-related plasma membrane protein rBAT/SLC3A12016
Author(s)
Nagamori S, Wiriyasermkul P, Guarch ME, Okuyama H, Nakagomi S, Tadagaki K, Nishinaka Y, Bodoy S, Takafuji K, Okuda S, Kurokawa J, Ohgaki R, Nunes V, Palacín M, Kanai Y.
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Journal Title
Proc Natl Acad Sci U S A
Volume: 113
Pages: 775-780
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Transport of 3-fluoro-l-α-methyl-tyrosine (FAMT) by organic ion transporters explains renal background in [18F] FAMT positron emission tomography.2016
Author(s)
Wei L, Tominaga H, Ohgaki R, Wiriyasermkul P, Hagiwara K, Okuda S, Kaira K, Kato Y, Oriuchi N, Nagamori S, Kanai Y.
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Journal Title
J Pharmacol Sci
Volume: 130
Pages: 101-109
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] CD98 is a novel prognostic indicator for patients with stage III/IV hypopharyngeal squamous cell carcinoma.2015
Author(s)
Toyoda M, Kaira K, Shino M, Sakakura K, Takahashi K, Takayasu Y, Tominaga H, Oriuchi N, Nikkuni O, Suzuki M, Iijima M, Tsukamoto N, Nagamori S, Kanai Y, Oyama T, Chikamatsu K.
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Journal Title
Head Neck
Volume: in press
Pages: 1569-1574
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Development of a Widely Usable Amino Acid Tracer: ⁷⁶Br-α-Methyl-Phenylalanine for Tumor PET Imaging.2015
Author(s)
Hanaoka H, Ohshima Y, Suzuki Y, Yamaguchi A, Watanabe S, Uehara T, Nagamori S, Kanai Y, Ishioka NS, Tsushima Y, Endo K, Arano Y.
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Journal Title
J Nucl Med.
Volume: 56
Pages: 791-7
DOI
Related Report
Peer Reviewed
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[Journal Article] Expression of Amino Acid Transporters (LAT1 and ASCT2) in Patients with Stage III/IV Laryngeal Squamous Cell Carcinoma.2015
Author(s)
Nikkuni O, Kaira K, Toyoda M, Shino M, Sakakura K, Takahashi K, Tominaga H, Oriuchi N, Suzuki M, Iijima M, Asao T, Nishiyama M, Nagamori S, Kanai Y, Oyama T, Chikamatsu K.
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Journal Title
Pathol Oncol Res.
Volume: 21
Pages: 1175-1181
DOI
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Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Molecular architecture of the stria vascularis membrane transport system, which is essential for physiological functions of the mammalian cochlea2015
Author(s)
Uetsuka S, Ogata G, Nagamori S, Isozumi N, Nin F, Yoshida T, Komune S, Kitahara T, Kikkawa Y, Inohara H, Kanai Y, Hibino H.
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Journal Title
Eur J Neurosci
Volume: 42
Pages: 1984-2002
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] Prognostic significance of L-type amino acid transporter 1 (LAT1) expression in cutaneous melanoma.2015
Author(s)
Shimizu A, Kaira K, Kato M, Yasuda M, Takahashi A, Tominaga H, Oriuchi N, Nagamori S, Kanai Y, Oyama T, Asao T, Ishikawa O.
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Journal Title
Melanoma Res
Volume: 25
Pages: 399-405
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] BPA-dipeptides, novel boron delivery agents for boron neutron capture therapy, targeting the oligopeptide transporters2018
Author(s)
Junji Miyabe, Ryuichi Ohgaki, Keijiro Saito, Ling Wei, Suguru Okuda, Shushi Nagamori, Kazuo Yoshino, Hidenori Inohara, Yoshikatsu Kanai
Organizer
大阪大学医学系研究フォーラム 第10回若手研究フォーラム
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[Presentation] Inhibition kinetics, sidedness of action, and transporter-mediated uptake of the sodium/glucose cotransporter (SGLT) 2 inhibitor canagliflozin: implications for its pharmacodynamic and pharmacokinetic features2016
Author(s)
Ling Wei, Ryuichi Ohgaki, Kazunori Yamada, Taiki Hara, Chiaki Kuriyama, Suguru Okuda, Kiichiro Ueta, Masaharu shiotani, Shushi Nagamori and Yoshikatsu Kanai
Organizer
International and Interdisciplinary Symposium 2016 “Towards a New Era of Cardiovascular Research”
Place of Presentation
東京
Year and Date
2016-07-12
Related Report
Int'l Joint Research
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[Presentation] Inhibition kinetics, sidedness of action, and transporter-mediated uptake of the sodium/glucose cotransporter (SGLT) 2 inhibitor canagliflozin: implications for its pharmacodynamic and pharmacokinetic features2016
Author(s)
Ohgaki R, Wei L, Yamada K, Hara T, Kuriyama C, Okuda S, Ueta K, Leclercq L, Mamidi RN, Shiotani M, Nagamori S, Kanai Y
Organizer
76th American Diabetes Association Scientific Sessions
Place of Presentation
New Orleans, Louisiana, US
Year and Date
2016-06-10
Related Report
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