Functional analysis of glycoproteins in tumor spheres

• Project/Area Number: 20K07629
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Osaka International Cancer Institute
• Principal Investigator: Ohkawa Yuki 地方独立行政法人大阪府立病院機構大阪国際がんセンター(研究所), その他部局等, 糖鎖オンコロジー部・研究員 (40723896)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2021: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
• Keywords: 糖鎖 / がん / スフェロイド / N型糖鎖 / 糖タンパク質

Outline of Research at the Start

幹細胞マーカーを発現するがん細胞は、がん幹細胞と呼ばれ、化学療法や放射線療法に強い抵抗性を示す。また、がん幹細胞の特性としてスフェロイドの形成(足場非依存的増殖)が知られており、スフェロイド形成の制御が新たながんの治療法として期待されている。本研究では、がんのスフェロイド形成を制御する糖タンパク質に注目し、その作用機構を明らかにする。またその糖タンパク質が、がんの治療に効果があるかどうかを検証する。

Outline of Final Research Achievements

Fetuin-A: α-2-HS-glycoprotein, is secreted from the liver and can be detected in human blood. The function of Fetuin-A against cancer is not clear to date. In this study, we found that Fetuin-A increased cell growth rate and resistance in lung cancer cells against anti-cancer drug treatment. Additionally, we clarified a part of its molecular mechanisms.

Academic Significance and Societal Importance of the Research Achievements

Fetuin-Aの癌に対する機能を世界に先駆けて明らかにした。またその作用メカニズムの一端を明らかにしたことから、Fetuin-Aを標的にした、新たな治療法の開発が期待される。

Research Products

• [Journal Article] Possible regulation of ganglioside GD3 synthase gene expression with DNA methylation in human glioma cells. (2023)
  • Author(s): Yurie Yamamoto, Ken Higashimoto, Yuki Ohkawa, Hidenobu Soejima, Kei Kaneko, Yuhsuke Ohmi, Keiko Furukawa, Koichi Furukawa
  • Journal Title: Glycoconj. J Volume: 40 Issue: 3 Pages: 1-10
  • DOI: 10.1007/s10719-023-10108-9
  • Peer Reviewed / Open Access
• [Journal Article] Core Fucosylation Is Required for the Secretion of and the Enzymatic Activity of SOD3 in Nonsmall-Cell Lung Cancer Cells (2023)
  • Author(s): Ohkawa Yuki、Kitano Masato、Maeda Kento、Nakano Miyako、Kanto Noriko、Kizuka Yasuhiko、Seike Masahiro、Azuma Arata、Yamaguchi Yoshiki、Ookawara Tomomi、Miyoshi Eiji、Taniguchi Naoyuki
  • Journal Title: Antioxid Redox Signal. Volume: - Issue: 16-18 Pages: 227-234
  • DOI: 10.1089/ars.2022.0010
  • Peer Reviewed / Open Access
• [Journal Article] The ulcerative colitis-associated gene FUT8 regulates the quantity and quality of secreted mucins (2022)
  • Author(s): Cantero-Recasens Gerard、Burballa Carla、Ohkawa Yuki、Fukuda Tomohiko、Harada Yoichiro、Curwin Amy J.、Brouwers Nathalie、Thun Gian A.、Gu Jianguo、Gut Ivo、Taniguchi Naoyuki、Malhotra Vivek、IBD Character Consortium
  • Journal Title: Proceedings of the National Academy of Sciences Volume: 119 Issue: 43 Pages: 1-12
  • DOI: 10.1073/pnas.2205277119
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Signaling domains of cancer-associated glycolipids. Tribute to Professor Sen-itiroh Hakomori (2022)
  • Author(s): Furukawa, K., Ohmi, Y., Hamamura, K., Kondo, Y., Ohkawa, Y., Kaneko, K., Hashimoto, N., Farhana, Y., Bhuiyan, R.H., Tajima, O., Furukawa, K.
  • Journal Title: Glycoconj. J. Volume: 39 Issue: 2 Pages: 145-155
  • DOI: 10.1007/s10719-022-10051-1
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] N-glycan branching enzymes involved in cancer, Alzheimer's disease and COPD and future perspectives (2022)
  • Author(s): Taniguchi Naoyuki、Ohkawa Yuki、Maeda Kento、Kanto Noriko、Johnson Emma Lee、Harada Yoichiro
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 633 Pages: 68-71
  • DOI: 10.1016/j.bbrc.2022.09.027
  • Peer Reviewed
• [Journal Article] The expression of keratan sulfate in malignant melanoma enhances the adhesion and invasion activity of melanoma cells (2022)
  • Author(s): Tachibana Kota、Ohkawa Yuki、Kanto Noriko、Maeda Kento、Ohe Shuichi、Isei Taiki、Harada Yoichiro、Taniguchi Naoyuki
  • Journal Title: The Journal of Dermatology Volume: 49 Issue: 10 Pages: 1027-1036
  • DOI: 10.1111/1346-8138.16506
  • Peer Reviewed
• [Journal Article] Peptide Sequence Mapping around Bisecting GlcNAc-Bearing N-Glycans in Mouse Brain. (2021)
  • Author(s): Ohkawa Y, Kizuka Y, Takata M, Nakano M, Ito E, Mishra SK, Akatsuka H, Harada Y, Taniguchi N.
  • Journal Title: Int. J. Mol. Sci. Volume: 22 Issue: 16 Pages: 8579-8579
  • DOI: 10.3390/ijms22168579
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Lack of GD3 synthase (St8sia1) attenuates malignant properties of gliomas in genetically engineered mouse model. (2021)
  • Author(s): Ohkawa, Y., Zhang, P., Momota, H., Kato, A., Hashimoto, N., Ohmi, Y., Bhuiyan, R.H., Natsume, A., Wakabayashi, T., Furukawa, K, Furukawa K.
  • Journal Title: Cancer Sci. Volume: 112 Issue: 9 Pages: 3756-3768
  • DOI: 10.1111/cas.15032
  • Peer Reviewed / Open Access
• [Journal Article] Glycan quality control in and out of the endoplasmic reticulum of mammalian cells (2021)
  • Author(s): Harada Yoichiro、Ohkawa Yuki、Maeda Kento、Taniguchi Naoyuki
  • Journal Title: The FEBS Journal Volume: Online ahead of print Issue: 22 Pages: 7147-7162
  • DOI: 10.1111/febs.16185
  • Peer Reviewed
• [Journal Article] Extracellular Vesicles and Glycosylation (2021)
  • Author(s): Harada Yoichiro、Ohkawa Yuki、Maeda Kento、Kizuka Yasuhiko、Taniguchi Naoyuki
  • Journal Title: The Role of Glycosylation in Health and Disease Volume: 1325 Pages: 137-149
  • DOI: 10.1007/978-3-030-70115-4_6
  • ISBN: 9783030701147, 9783030701154
  • Peer Reviewed
• [Journal Article] Ganglioside GD2 Enhances the Malignant Phenotypes of Melanoma Cells by Cooperating with Integrins. (2021)
  • Author(s): Yesmin, F., Bhuiyan, R.H., Ohmi, Y., Yamamoto, S., Kaneko, K., Ohkawa, Y., Zhang, P., Hamamura, K., Cheung, N-K.V., Kotani, N., Honke, K., Okajima, T., Kambe, M., Tajima, O., Furukawa, K., Furukawa, K.
  • Journal Title: Int. J. Mol. Sci. Volume: 23 Issue: 1 Pages: 423-442
  • DOI: 10.3390/ijms23010423
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] St8sia1-deficiency in mice alters tumor environments of gliomas, leading to reduced disease severity (2021)
  • Author(s): Zhang, P., Ohkawa, Y., Yamamoto, S., Momota, H., Kato, A., Kaneko, K., Natsume, A., Farhana, Y., Ohmi, Y., Okajima, T., Bhuiyan, R.H., Wakabayashi, T., Furukawa, K., Furukawa, K.
  • Journal Title: Nagoya Journal of Medical Science Volume: 83 Issue: 3 Pages: 535-549
  • DOI: 10.18999/nagjms.83.3.535
  • NAID: 120007147350
  • ISSN: 0027-7622
  • URL: https://nagoya.repo.nii.ac.jp/records/2001444
  • Peer Reviewed / Open Access
• [Journal Article] Keratan sulfate-based glycomimetics using Langerin as a target for COPD: lessons from studies on Fut8 and core fucose (2021)
  • Author(s): Ohkawa Yuki、Harada Yoichiro、Taniguchi Naoyuki
  • Journal Title: Biochemical Society Transactions Volume: 49 Issue: 1 Pages: 441-453
  • DOI: 10.1042/bst20200780
  • Peer Reviewed / Open Access
• [Journal Article] Synthesis and Screening of α-Xylosides in Human Glioblastoma Cells (2020)
  • Author(s): Kalita Mausam、Villanueva-Meyer Javier、Ohkawa Yuki、Kalyanaraman Chakrapani、Chen Katharine、Mohamed Esraa、Parker Matthew F. L.、Jacobson Matthew P.、Phillips Joanna J.、Evans Michael J.、Wilson David M.
  • Journal Title: Molecular Pharmaceutics Volume: 18 Issue: 1 Pages: 451-460
  • DOI: 10.1021/acs.molpharmaceut.0c00839
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Glycometabolic Regulation of the Biogenesis of Small Extracellular Vesicles (2020)
  • Author(s): Harada Yoichiro、Nakajima Kazuki、Suzuki Takehiro、Fukushige Tomoko、Kondo Kiyotaka、Seino Junichi、Ohkawa Yuki、Suzuki Tadashi、Inoue Hiromasa、Kanekura Takuro、Dohmae Naoshi、Taniguchi Naoyuki、Maruyama Ikuro
  • Journal Title: Cell Reports Volume: 33 Issue: 2 Pages: 108261-108261
  • DOI: 10.1016/j.celrep.2020.108261
  • Peer Reviewed / Open Access
• [Journal Article] Heparan Sulfate Synthesized byExt1Regulates Receptor Tyrosine Kinase Signaling and Promotes Resistance to EGFR Inhibitors in GBM (2020)
  • Author(s): Ohkawa Yuki、Wade Anna、Lindberg Olle R.、Chen Katharine Y.、Tran Vy M.、Brown Spencer J.、Kumar Anupam、Kalita Mausam、James C. David、Phillips Joanna J.
  • Journal Title: Molecular Cancer Research Volume: 19 Issue: 1 Pages: 150-161
  • DOI: 10.1158/1541-7786.mcr-20-0420
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] True significance of N-acetylglucosaminyltransferases GnT-III, V and α1,6 fucosyltransferase in epithelial-mesenchymal transition and cancer (2020)
  • Author(s): Taniguchi Naoyuki、Ohkawa Yuki、Maeda Kento、Harada Yoichiro、Nagae Masamichi、Kizuka Yasuhiko、Ihara Hideyuki、Ikeda Yoshitaka
  • Journal Title: Molecular Aspects of Medicine Volume: in press Pages: 100905-100905
  • DOI: 10.1016/j.mam.2020.100905
  • Peer Reviewed
• [Journal Article] Aminoglycosides are efficient reagents to induce readthrough of premature termination codon in mutant B4GALNT1 genes found in families of hereditary spastic paraplegia (2020)
  • Author(s): Yesmin F, Bhuiyan RH, Ohmi Y, Ohkawa Y, Tajima O, Okajima T, Furukawa K, Furukawa K.
  • Journal Title: J Biochem. Volume: 168 Issue: 2 Pages: 103-112
  • DOI: 10.1093/jb/mvaa041
  • NAID: 40022308727
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Novel molecular mechanisms for roles of gangliosides in the nervous system elucidated by genetic engineering. (2020)
  • Author(s): Furukawa, K., Ohmi, Y., Yesmin, F., Tajima, O., Kondo, Y., Pu Zhang, P., Hashimoto, N., Ohkawa, Y., Bhuiyan, R.H., Furukawa, K.
  • Journal Title: Int. J. Mol. Sci. Volume: 21 Issue: 6 Pages: 1906-1906
  • DOI: 10.3390/ijms21061906
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] がんや前がん病変におけるグリコサミノグリカンの機能解析とその応用 (2023)
  • Author(s): 大川祐樹
  • Organizer: 第31回プロテオグライカンフォーラム
  • Invited
• [Presentation] がん及び炎症病変における糖鎖の機能解析 (2022)
  • Author(s): 大川祐樹
  • Organizer: 第41回日本糖質学会年会
  • Invited
• [Presentation] グルコースががんの悪性度を増強する (2022)
  • Author(s): 岡本朋子、大川祐樹、貫戸紀子、前田賢人、若松透、田宮大地、竹中聡、原田陽一郎、三善英知、谷口直之
  • Organizer: 第41回日本糖質学会年会
• [Presentation] The expression of keratan sulfate in malignant melanoma enhances adhesion and invasion activity of melanoma cells (2022)
  • Author(s): Yuki Ohkawa, Kota Tachibana, Noriko Kanto, Kento Maeda, Shuichi Ohe, Taiki Isei, Yoichiro Harada, Naoyuki Taniguchi
  • Organizer: 第81回日本癌学会学術総会
• [Presentation] グライコプロテオミクスによる糖転移酵素GnT-IIIのタンパク質認識機構の解析 (2022)
  • Author(s): 大川祐樹、木塚康彦、高田実咲、中の三弥子、伊藤恵美、Sushil K Mishra、赤塚晴奈、原田陽一郎、谷口直之
  • Organizer: 第95回日本生化学会大会
• [Presentation] グルコースによって発現誘導される分子の同定とその機能解析 (2022)
  • Author(s): 岡本朋子、大川祐樹、中野可菜、中の三弥子、貫戸紀子、前田賢人、原田陽一郎、三善英知、谷口直之
  • Organizer: 第68回日本生化学会近畿支部例会
• [Presentation] COPD症状を緩和するケラタン硫酸二糖L4およびその誘導体の分子作用メカニズムの解明 (2021)
  • Author(s): 大川祐樹、貫戸紀子、中の三弥子、藤縄玲子、木塚康彦、原田陽一郎、田村純一、谷口直之
  • Organizer: 第21回 関西グライコサイエンスフォーラム
• [Presentation] Functional analysis of langerin against keratan sulfate disaccharide L4 and derivatives in langerin knockout mice (2021)
  • Author(s): Yuki Ohkawa, Noriko Kanto, Miyako Nakano, Reiko Fujinawa, Yasuhiko Kizuka, Yoichiro Harada, Jun-ichi Tamura, Naoyuki Taniguchi
  • Organizer: 3rd Australasian Glycoscience Symposium
  • Int'l Joint Research
• [Presentation] Induction of bisecting GlcNAc by microenvironment enhances malignant phenotypes in tumor (2021)
  • Author(s): Yuki Ohkawa, Kana Nakano, Noriko Kanto, Miyako Nakano, Eiji Miyoshi, Yoichiro Harada, Naoyuki Taniguchi
  • Organizer: 第80回 日本癌学会学術総会
• [Presentation] ケラタン硫酸型グライコミメティクスによるCOPD治療効果の分子作用メカニズムの解明 (2021)
  • Author(s): 大川祐樹、貫戸紀子、中の三弥子、藤縄玲子、木塚康彦、原田陽一郎、田村純一、谷口直之
  • Organizer: 第40回 日本糖質学会年会
• [Presentation] がんの悪性度を制御する機能性糖鎖の作動メカニズム (2021)
  • Author(s): 大川祐樹
  • Organizer: 第94回 日本生化学会大会
• [Presentation] 低グルコースはN型糖鎖の構造変化を介してがんスフェロイドの形成を促進する (2020)
  • Author(s): 大川祐樹、中野可菜、中の三弥子、木塚康彦、原田陽一郎、三善英知、谷口直之
  • Organizer: 第79回 日本癌学会学術総会
• [Presentation] Anti-inflammatory effect of keratan sulfate disaccharide L4 and derivatives through langerin in COPD (2020)
  • Author(s): Yuki Ohkawa, Noriko Kanto, Miyako Nakano, Reiko Fujinawa, Yasuhiko Kizuka, Yoichiro Harada, Jun-ichi Tamura, Naoyuki Taniguchi
  • Organizer: Society for Glycobiology 2020 Annual Meeting
  • Int'l Joint Research
• [Presentation] ケラタン硫酸二糖L4及び誘導体のlangerinを介したCOPDモデルマウスへの効果 (2020)
  • Author(s): 大川祐樹、貫戸紀子、中の三弥子、藤縄玲子、木塚康彦、原田陽一郎、田村純一、谷口直之
  • Organizer: 第39回 日本糖質学会年会
• [Presentation] がん悪性形質におけるバイセクト型N型糖鎖の機能解析 (2020)
  • Author(s): 中野可菜、大川祐樹、中の三弥子、原田陽一郎、三善英知、谷口直之
  • Organizer: 第39回 日本糖質学会年会
• [Book] BIO EX-press, 大阪国際がんセンター特集 (2022)
  • Author(s): 大川祐樹、谷口直之
  • Total Pages: 6
  • Publisher: ダイアローグ株式会社
• [Book] 週刊医学のあゆみ (2022)
  • Author(s): 大川祐樹
  • Total Pages: 5
  • Publisher: 医歯薬出版株式会社
• [Remarks] 大阪国際がんセンター・研究所・部紹介・糖鎖オンコロジー部
  • URL: https://oici.jp/laboratory/department/tousa/