Role of sphingosine 1-phosphate signaling on tumor metastasis

• Project/Area Number: 26460341
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General pharmacology
• Research Institution: Kobe University
• Principal Investigator: Kajimoto Taketoshi 神戸大学, 大学院医学研究科, 助教 (00509953)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 生理活性物質 / シグナル伝達 / エクソソーム / スフィンゴシン1-リン酸 / スフィンゴシンキナーゼ / 癌 / スフィンゴシン-1-リン酸 / スフィンゴシン-1-リン酸受容体 / 癌転移

Outline of Final Research Achievements

Exosomes are small membrane-bound vesicles released from a variety of physiological cells or tumor cells and include much functional proteins and RNAs as cargo. Recently we discovered new mechanism of Sphingosine 1-phosphate (S1P) signaling-regulated cargo sorting into exosomes. However the role of S1P signaling on sorting of cargoes that relates to tumor metastasis such as c-Met or miRNA into exosomes is still unclear. Here, we found S1P-signaling also plays a critical role in exosomal sorting of these tumor metastasis-related cargoes. Now we continue to try some in vitro study to figure out the importance of S1P signaling-induced exosomal cargo sorting on tumor metastasis. If completing this study we would expect that S1P signaling becomes innovative drug target for tumor metastasis.

Research Products

• [Journal Article] Extracellular α-synuclein induces sphingosine 1-phosphate receptor subtype 1 uncoupled from inhibitory G-protein leaving β-arrestin signal intact. (2017)
  • Author(s): Zhang L, Okada T, Badawy SM, Hirai C, Kajimoto T, Nakamura SI.
  • Journal Title: Scientific Reports Volume: 7 Issue: 1 Pages: 44248-44248
  • DOI: 10.1038/srep44248
  • NAID: 120006380401
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Impairment of PDGF-induced chemotaxis by extracellular α-synuclein through selective inhibition of Rac1 activation (2016)
  • Author(s): Okada, T., Hirai, C., Badawy, S., Zhang, L., Kajimoto, T., Nakamura, SI.
  • Journal Title: Scientific Reports Volume: 6 Issue: 1 Pages: 37810-37810
  • DOI: 10.1038/srep37810
  • NAID: 120005898707
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] エキソソームの形成機構 (2015)
  • Author(s): 梶本 武利、岡田 太郎、中村 俊一
  • Journal Title: 細胞工学 Volume: Vol.34 No.2 Pages: 168-173
• [Presentation] Sphingosine 1-phosphate signaling on multivesicular endosome triggers sorting of protein cargo into exosomes (2015)
  • Author(s): Taketoshi Kajimoto*, Taro Okada, Satoshi Miya, Lifang Zhang, Shun-ichi Nakamura
  • Organizer: 2015 ASCB Annual Meeting
  • Place of Presentation: San Diego, USA
  • Year and Date: 2015-12-12
  • Int'l Joint Research
• [Presentation] Role of S1P signaling on cargo loading for exosome maturation (2015)
  • Author(s): Taketoshi Kajimoto*, Shun-ichi Nakamura
  • Organizer: University of Washington-Kobe University Symposium on Cell Signaling
  • Place of Presentation: Seattle, USA
  • Year and Date: 2015-09-10
  • Int'l Joint Research / Invited
• [Presentation] Sphingosine 1-phosphate signaling triggers exosomal protein sorting (2014)
  • Author(s): 梶本 武利、岡田 太郎、宮 聡志、○張 麗芳、中村 俊一
  • Organizer: 神戸大学・ワシントン大学国際合同シンポジウム
  • Place of Presentation: 神戸、日本
  • Year and Date: 2014-12-15 – 2014-12-16
• [Presentation] エクソソームへの積み荷ソーティングにおける生理活性物質スフィンゴシン１-リン酸の役割 (2014)
  • Author(s): ○梶本 武利、岡田 太郎、宮 聡志、張 麗芳、中村 俊一
  • Organizer: 第118回 日本薬理学会近畿部会
  • Place of Presentation: 岡山、日本
  • Year and Date: 2014-06-20
• [Presentation] スフィンゴシン１-リン酸シグナリングによるエクソソームへの積み荷ソーティング機構 (2014)
  • Author(s): ○梶本 武利、岡田 太郎、宮 聡志、張 麗芳、中村 俊一
  • Organizer: 第66回 日本細胞生物学会大会
  • Place of Presentation: 奈良、日本
  • Year and Date: 2014-06-11 – 2014-06-13
• [Presentation] Sphingosine 1-phosphate signaling regulates exosomal cargo sorting (2014)
  • Author(s): ○梶本 武利、岡田 太郎、宮 聡志、張 麗芳、中村 俊一
  • Organizer: 2014 ASBMB Annual Meeting（アメリカ生化学・分子生物学会大会）
  • Place of Presentation: San Diego, USA
  • Year and Date: 2014-04-26 – 2014-04-30
• [Remarks] 神戸大学大学院医学研究科生化学・分子生物学講座生化学分野
  • URL: http://www.med.kobe-u.ac.jp/biochemistry/Home.html
• [Remarks] 神戸大学 医学研究科 中村研究室
  • URL: http://www.med.kobe-u.ac.jp/biochemistry/Home.html