神経線維腫症の神経系分化異常と腫瘍化に関わる細胞内外シグナル解明と治療戦略の構築

2021 Fiscal Year Annual Research Report

• Project/Area Number: 19H03772
• Research Institution: Kumamoto University
• Principal Investigator: 荒木 令江 熊本大学, 大学院生命科学研究部(医), 准教授 (80253722)
• Co-Investigator(Kenkyū-buntansha): 江良 択実 熊本大学, 発生医学研究所, 教授 (00273706) ; 北川 孝雄 北海道医療大学, 先端研究推進センター, 助教 (20614928) ; 武笠 晃丈 熊本大学, 大学院生命科学研究部(医), 教授 (90463869)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 神経線維腫症 / NF1 / NF2 / 融合プロテオミクス / ネットワーク解析

Outline of Annual Research Achievements

神経線維腫症は、多発性神経線維腫に加え悪性腫瘍等を伴う１型(NF1)、及び類似症状に加え中枢神経系腫瘍を高頻度に伴う２型(NF2)からなる治療困難な遺伝性疾患である。本研究では、両疾患の関わる神経系分化異常と腫瘍発生機序の解明、および治療標的の開発を目的としている。
本年度は、昨年に引き続き様々な細胞において樹立を進めている各種NF病態モデル細胞を用いて、特異的な神経系分化異常および腫瘍化に関わる細胞内分子群の異常ネットワークを独自のトランスクリプトミクス・プロテオミクスを介して詳細に解析した。同時進行として、新しいインタラクトーム解析技術法の最適化を行い、これを用いて、NF遺伝子産物に関わって大きく変動する分子の結合コンプレックスとそれを介したネットワークを解析した。最適化されたこれらの方法論から得られた情報をプロテオミクスを中心に融合マイニングし、NF欠損モデル細胞およびNF1欠損悪性末梢神経鞘腫MPNST細胞等の細胞内で、NFの欠損によって最も影響を与えられているネットワーク因子群を部分的に絞り込んだ。NF1に関して、特異的に活性化する複数のターゲットとなりうる同定因子群で、特にアポトーシス阻害やタンパク質合成に関わるTCTP、これに結合するタンパク質翻訳伸長因子(EF1family)群、およびこれらに関連した活性化シグナルが特異的な標的候補となることが判明した。NF2に関しては、一連の糖鎖修飾膜タンパク質群とインテグリンの相互作用とNF2タンパク質（Merlin)が関連している可能性が示された。これらの標的候補群に対してそれぞれの分子群のsiRNAおよび各種阻害剤の効果を細胞レベルで検討し、標的シグナルの一部を絞り込むことに成功した。
本研究から得られた結果は、NFの新規治療戦略の構築のための重要な基礎情報となる可能性が高い。

Research Progress Status

令和3年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

令和3年度が最終年度であるため、記入しない。

Research Products

• [Int'l Joint Research] 国立コンケン大学(タイ)
  • Country Name: THAILAND
  • Counterpart Institution: 国立コンケン大学
• [Int'l Joint Research] マルタ国立大学(マルタ)
  • Country Name: MALTA
  • Counterpart Institution: マルタ国立大学
• [Journal Article] Establishment and characterization of a novel cancer stem‐like cell of cholangiocarcinoma (2023)
  • Author(s): Panawan Orasa, Silsirivanit Atit、Chang Chih‐Hsiang、Putthisen Siyaporn、Boonnate Piyanard、Yokota Taro、Nishisyama‐Ikeda Yuki、Detarya Marutpong、Sawanyawisuth K、Kaewkong W、Muisuk K、Luang S、Vaeteewoottacharn K、Kariya R、Yano H、Komohara Y、Ohta K、Okada S、Wongkham S、Araki Norie
  • Journal Title: Cancer Science Volume: in press Pages: in press
  • DOI: 10.1111/cas.15812
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Data for method development of water droplet-in-oil digestion approach (2023)
  • Author(s): Takeshi Masuda, Norie Araki, Sumio Ohtsuki
  • Journal Title: Journal of Proteome Data and Methods Volume: 5 Pages: 1
  • DOI: 10.14889/jpdm.2023.0001
  • Peer Reviewed / Open Access
• [Journal Article] Targeting alpha2,3-sialylated glycan in glioma stem-like cells by Maackia amurensis lectin-II: A promising strategy for glioma treatment (2022)
  • Author(s): Putthisen Siyaporn、Silsirivanit Atit、Panawan Orasa、Niibori-Nambu Akiko、Nishiyama-Ikeda Yuki、Ma-In Prasertsri、Luang Sukanya、Ohta Kunimasa、Muisuk Kanha、Wongkham Sopit、Araki Norie
  • Journal Title: Experimental Cell Research Volume: 410 Pages: 112949～112949
  • DOI: 10.1016/j.yexcr.2021.112949
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Water Droplet-in-Oil Digestion Method for Single-Cell Proteomics (2022)
  • Author(s): Masuda Takeshi、Inamori Yuma、Furukawa Arisu、Yamahiro Maki、Momosaki Kazuki、Chang Chih-Hsiang、Kobayashi Daiki、Ohguchi Hiroto、Kawano Yawara、Ito Shingo、Araki Norie、Ong Shao-En、Ohtsuki Sumio
  • Journal Title: Analytical Chemistry Volume: 94 Pages: 10329～10336
  • DOI: 10.1021/acs.analchem.1c05487
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] SIRT7 suppresses energy expenditure and thermogenesis by regulating brown adipose tissue functions in mice (2022)
  • Author(s): Yoshizawa Tatsuya、Sato Yoshifumi、Sobuz Shihab U.、Mizumoto Tomoya、Tsuyama Tomonori、Karim Md. Fazlul、Miyata Keishi、Tasaki Masayoshi、Yamazaki Masaya、Kariba Yuichi、Araki Norie、Araki Eiichi、Kajimura Shingo、Oike Yuichi、Braun Thomas、Bober Eva、Auwerx Johan、Yamagata Kazuya
  • Journal Title: Nature Communications Volume: 13 Pages: 7439
  • DOI: 10.1038/s41467-022-35219-z
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] AT-hook DNA-binding motif-containing protein one knockdown downregulates EWS-FLI1 transcriptional activity in Ewing’s sarcoma cells (2022)
  • Author(s): Kitagawa Takao、Kobayashi Daiki、Baron Byron、Okita Hajime、Miyamoto Tatsuo、Takai Rie、Paudel Durga、Ohta Tohru、Asaoka Yoichi、Tokunaga Masayuki、Nakagawa Koji、Furutani-Seiki Makoto、Araki Norie、Kuramitsu Yasuhiro、Kobayashi Masanobu
  • Journal Title: PLOS ONE Volume: 17 Pages: 0269077
  • DOI: 10.1371/journal.pone.0269077
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Emerging roles of GALNT5 on promoting EGFR activation in cholangiocarcinoma: a mechanistic insight. (2022)
  • Author(s): Marutpong Detarya 1, Worachart Lert-Itthiporn 1, Panupong Mahalapbutr 1, Methus Klaewkla 2, Supannika Sorin 1, KanlayaneeSawanyawisuth, Atit Silsirivanit, Wunchana Seubwai, Chaisiri Wongkham, Norie Araki, Sopit Wongkham
  • Journal Title: American Journal of Cancer Research Volume: 12 Pages: 4140-4159
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Bioinformatic Prediction of Novel Signaling Pathways of Apoptosis-inducing Factor, Mitochondrion-associated 3 (AIFM3) and Their Roles in Metastasis of Cholangiocarcinoma Cells (2021)
  • Author(s): CHUA-ON DARAPORN、PROUNGVITAYA TANAKORN、TECHASEN ANCHALEE、LIMPAIBOON TEMDUANG、ROYTRAKUL SITTIRUK、TUMMANATSAKUN DOUNGDEAN、ARAKI NORIE、PROUNGVITAYA SIRIPORN
  • Journal Title: Cancer Genomics - Proteomics Volume: 19 Pages: 35～49
  • DOI: 10.21873/cgp.20302
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] EGFR-Targeted Pentacyclic Triterpene Analogues for Glioma Therapy (2021)
  • Author(s): Ciftci Halil I.、Radwan Mohamed O.、Sever Belgin、Hamdy Ahmed K.、Emirda? Safiye、Ulusoy N. Gokce、Sozer Ece、Can Mustafa、Yayli Nurettin、Araki Norie、Tateishi Hiroshi、Otsuka Masami、Fujita Mikako、Altintop Mehlika Dilek
  • Journal Title: International Journal of Molecular Sciences Volume: 22 Pages: 10945～10945
  • DOI: 10.3390/ijms222010945
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] TCTP interactomics in NF1-associated malignant tumor cells by affinity-purification and SWATH-MS (2021)
  • Author(s): Daiki Kobayashi, Norie Araki
  • Journal Title: Journal of Proteome Data and Methods Volume: 3 Pages: 2
  • DOI: 10.14889/jpdm.2021.0002
  • Peer Reviewed / Open Access
• [Journal Article] Purification, Characterization, and Gene Expression of Rice Endo-β-N-Acetylglucosaminidase, Endo-Os (2021)
  • Author(s): Maeda Megumi、Okamoto Naoko、Araki Norie、Kimura Yoshinobu
  • Journal Title: Frontiers in Plant Science Volume: 12 Pages: 647684
  • DOI: 10.3389/fpls.2021.647684
  • Peer Reviewed / Open Access
• [Journal Article] Water droplet-in-oil digestion method for single-cell proteomics (2021)
  • Author(s): Masuda Takeshi、Inamori Yuma、Furukawa Arisu、Momosaki Kazuki、Chang Chih-Hsiang、Kobayashi Daiki、Ohguchi Hiroto、Kawano Yawara、Ito Shingo、Araki Norie、Ong Shao-En、Ohtsuki Sumio
  • Journal Title: bioRxiv Volume: 12 Pages: 1
  • DOI: 10.1101/2021.12.13.472378
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] jPOSTを使ってプロテオーム解析をする (2022)
  • Author(s): 荒木令江
  • Organizer: 2022オンライン10 AJACS セミナー
  • Invited
• [Presentation] Large scale of global proteomics identify lipid metabolic pathways as a characteristic target of glioma stem-like cells (2022)
  • Author(s): Orasa Panawan, Atit Silsirivanit, Chih-Hsiang Chang, Siyaporn Putthisen, Worasak Kaewkong, Kanha Muisuk, Marutpong Detarya2, Sukanya Luang2 , Kulthida Vaeteewoottacharn, Ryosho Kariya, Seiji Okada, Sopit Wongkham and Norie Araki
  • Organizer: The 81st annual meeting of the Japanese cancer association
  • Int'l Joint Research
• [Presentation] 胆管がん由来がん幹細胞の樹立とプロテオミクスによる性状解析 (2022)
  • Author(s): 横田 太郎、パナワン オラサ、チーシャン チャン、シルシリヴァ ニト アチト、田上 久美子、中村 雅史、荒木 令江
  • Organizer: The 81st annual meeting of the Japanese cancer association
  • Int'l Joint Research
• [Presentation] Proteomics-Based Integrated Systems Biology for Tumor Research (2022)
  • Author(s): Norie Araki, Orasa Panawan, Marutpong Detarya, Akiko Niibori-Nambu, Chih-Hsiang Chang, Yuki Ikeda-Nishiyama, Daiki Kobayashi, Atit Silsirivanit
  • Organizer: 17th International Symposium of the Protein Society of Thailand
  • Int'l Joint Research / Invited
• [Presentation] Identification of the O-GalNAc glycoproteome related to the GALNT5 expression in cholangiocarcinoma (2022)
  • Author(s): Marutpong Detarya, Daiki Kobayashi, Atit Silsirivanit, Kanlayanee Sawanyawisuth, Sopit Wongkham, Chaisiri Wongkham, Norie Araki,
  • Organizer: 日本プロテオーム学会2022年大会 JPrOS2022(20th JHUPO)
• [Presentation] Global- and phospho-proteomics identify specific lipid metabolism pathways involved in the maintenance of glioma stem-like cells (2022)
  • Author(s): Orasa Panawan, Atit Silsirivanit, Chih-Hsiang Chang, Siyaporn Putthisen, Taro Yokota, Yuki Nishisyama-Ikeda , Akiko Niibori-Nambu, Norie Araki
  • Organizer: 日本プロテオーム学会2022年大会 JPrOS2022(20th JHUPO)
• [Presentation] 最適化グローバルプロテオミクスによる胆管がん由来幹細胞の性状解析 Characterization of cholangiocarcinoma stem-like cells by optimized global proteomics (2022)
  • Author(s): 横田 太郎、パナワン オラサ、チーシャン チャン、シルシリヴァ ニト アチト、田上 久美子、中村 雅史、荒木 令江
  • Organizer: 日本プロテオーム学会2022年大会 JPrOS2022(20th JHUPO)
• [Presentation] JPrOSヒストリア ー日本プロテオーム学会20年の歩みー (2022)
  • Author(s): 荒木令江
  • Organizer: 日本プロテオーム学会2022年大会 JPrOS2022(20th JHUPO)
  • Invited
• [Presentation] a) Identification of novel target signal networks of cancer stem cells by the functional integrated proteomics, b) Introduction of JPDM (2022)
  • Author(s): Araki, Norie, Panawan, Orasa, Chang, Chih-Hsiang, Yokota, Taro, Nishisyama-Ikeda, Yuki, Niibori-Nambu, Akiko, Silsirivanit, Atit
  • Organizer: HUPO 2022 world congress
  • Int'l Joint Research
• [Presentation] Advances and future of the Trans-Omics “What can we do with and what can we learn from trans-ome analyses? “ Analysis of therapeutic target networks of cancer stem cells by multi-omics (2022)
  • Author(s): Norie Araki, Orasa Panawan, Marutpong Detarya, Akiko Niibori-Nambu1, Chih-Hsiang Chang, Yuki Ikeda-Nishiyama, Daiki Kobayashi, Atit Silsirivanit
  • Organizer: 第45回 分子生物学会年会2023
  • Invited
• [Presentation] Establishment of cancer stem-like cells of cholangiocarcinoma, and their characterization by proteomics (2021)
  • Author(s): Panawan, O., Silsirivanit, A., Chang, C., Putthisen, S., Sawanyawisuth, K., Kaewkong, W., Muisuk, K., Detarya, M., Luang , S., Vaeteewoottacharn, K., Wongkham, C., Kariya, R., Okada, S., Wongkham, S., Araki, N.
  • Organizer: 10th Asia-Oceania Human Proteome Organization (AOHUPO) Congress in Busan, Korea
  • Int'l Joint Research
• [Presentation] Cell line-derived cancer stem-like cell: A useful tool for understanding cholangiocarcinoma (2021)
  • Author(s): Panawan, O., Phumphu, R., Silsirivanit, A., Putthisen, S., Sawanyawisuth, K., Kaewkong, W., Muisuk, K., Detarya, M., Luang , S., Vaeteewoottacharn, K., Wongkham, C., Kariya, R., Okada, S., Wongkham, S., Araki, N
  • Organizer: The 7th International Conference on Biochemistry and Molecular Biology (BMB 2021) in Phisanulok, Thailand
  • Int'l Joint Research
• [Presentation] Establishment and proteomic characterization of cholangiocarcinoma (2021)
  • Author(s): Orasa Panawan, Atit Silsirivanit, Chih-Hsiang Chang, Siyaporn Putthisen, Worasak Kaewkong, Kanha Muisuk, Marutpong Detarya2, Sukanya Luang2 , Kulthida Vaeteewoottacharn, Ryosho Kariya, Seiji Okada, Sopit Wongkham and Norie Araki
  • Organizer: The 18th Annual Meeting of the Japan Proteome Society JPrOS 2021
  • Int'l Joint Research
• [Presentation] Establishment and characterization of cancer stem-like cells of cholangiocarcinoma (2021)
  • Author(s): Orasa Panawan, Atit Silsirivanit, Chih-Hsiang Chang, Siyaporn Putthisen, Worasak Kaewkong, Kanha Muisuk, Marutpong Detarya2, Sukanya Luang2 , Kulthida Vaeteewoottacharn, Ryosho Kariya, Seiji Okada, Sopit Wongkham and Norie Araki
  • Organizer: The 80th annual meeting of the Japanese Cancer Asociation
  • Int'l Joint Research
• [Presentation] Identification of novel target signalings of neurofibromatosis type I-associated tumors by functional integrated-omics (2021)
  • Author(s): 荒木令江、小林大樹
  • Organizer: 第80回日本癌学会学術総会
  • Int'l Joint Research
• [Presentation] POSTdb: COVID-19データベースの構築 (2021)
  • Author(s): 6.吉沢明康、守屋勇樹、小林大樹、張智翔、奥田修二郎、田畑 剛、河野 信、幡野 敦、高見知代、松本雅記、山ノ内祥訓、荒木令江、岩崎未央、杉山直幸、福島敦史、田中 聡、五斗 進、石濱 泰
  • Organizer: トーゴーの日シンポジウム2021
• [Presentation] プロテオミクスが解き明かす細胞内の分子機構～初心者から専門家まで～ (2021)
  • Author(s): 荒木令江
  • Organizer: 第44回日本分子生物学会年会
  • Invited
• [Presentation] Establishment and characterization of a novel cancer stem cell derived from cholangiocarcinoma by proteomics (2021)
  • Author(s): Orasa Panawan, Atit Silsirivanit, Chih-Hsiang Chang, Siyaporn Putthisen, Worasak Kaewkong, Kanha Muisuk, Marutpong Detarya2, Sukanya Luang2 , Kulthida Vaeteewoottacharn, Ryosho Kariya, Seiji Okada, Sopit Wongkham and Norie Araki
  • Organizer: TheHUPO2021Reconnect world congress
  • Int'l Joint Research
• [Book] バイオDB とウエブツール "JPOST:アジア・オセアニアで最も有用なプロテオームデー タベース：jPOSTを使ってプロテオーム解析をする" (2022)
  • Author(s): 荒木令江
  • Total Pages: 248
  • Publisher: 羊土社
  • ISBN: 978-4-7581-0406-7
• [Remarks] JPOST Repository/Database
  • URL: https://jpostdb.org/
• [Remarks] 熊本大学大学院生命科学研究部腫瘍医学講座ホームページ
  • URL: https://tgbaraki.com/
• [Remarks] JPSTを使ってプロテオームを解析する
  • URL: https://togotv.dbcls.jp/en/20220316.html
• [Patent(Industrial Property Rights)] 前立腺がんの新規マーカー (2021)
  • Inventor(s): 荒木令江、笹尾明
  • Industrial Property Rights Holder: 熊本大学
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2021-184569