Identification of membrane fusion machineries for cancer cell invasion

• Project/Area Number: 26440064
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Functional biochemistry
• Research Institution: Tokyo University of Pharmacy and Life Science
• Principal Investigator: Inoue Hiroki 東京薬科大学, 生命科学部, 講師 (10294448)
• Co-Investigator(Renkei-kenkyūsha): TAGAYA Mitsuo 東京薬科大学, 生命科学部, 教授 (30179569)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 浸潤突起 / 細胞膜 / エンドソーム / 小胞輸送 / 細胞外基質分解 / MT1-MMP / SNARE / 浸潤性がん細胞

Outline of Final Research Achievements

Invadopodia in invasive cancer cells are actin-enriched structures with an ability to degrade extracellular matrix (ECM) and play crucial roles in invasion and metastasis. Membrane-type matrix metalloproteinase, MT1-MMP, is a major molecule that mediates ECM degradation at invadopodia and has been thought to be transported to invadopodia through several intracellular trafficking pathways. However, its molecular mechanisms remains elusive. In this study, we comprehensively identified several SNARE proteins as a membrane fusion machinery for MT1-MMP trafficking and invadopodia formation and revealed the roles of the SNAREs and their regulatory factor.

Research Products

• [Journal Article] Legionella effector Lpg1137 shuts down ER-mitochondria communication through cleavage of syntaxin 17 (2017)
  • Author(s): Arasaki, K., Mikami, Y. Shames, S., Inoue, H., Wakana, Y. and Tagaya, M.
  • Journal Title: Nat. Commun. Volume: 印刷中
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] SNARE-associated proteins and receptor trafficking. (2016)
  • Author(s): Inoue, H., Tani, K. and Tagaya, M.
  • Journal Title: Receptors & Clin. Investg. Volume: 3
  • DOI: 10.14800/rci.1377
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] CARTS biogenesis requires VAP-lipid transfer protein complexes functioning at the endoplasmic reticulum-Golgi interface. (2015)
  • Author(s): Wakana Y., Kotake R., Oyama N., Murate M., Kobayashi T., Arasaki K., Inoue H., Tagaya M.
  • Journal Title: Mol. Biol Cell Volume: 26 Issue: 25 Pages: 4686-4699
  • DOI: 10.1091/mbc.e15-08-0599
  • Peer Reviewed / Open Access
• [Journal Article] The NESH/Abi-3-based WAVE2 complex is functionally distinct from the Abi-1-based WAVE2 complex. (2015)
  • Author(s): Sekino, S., Kashiwagi, Y., Kanazawa, H., Takada, K., Baba, T., Sato, S., Inoue, H., Kojima, M. and Tani, K.
  • Journal Title: Cell Commun. Signal. Volume: 13 Issue: 1 Pages: 41-41
  • DOI: 10.1186/s12964-015-0119-5
  • Peer Reviewed / Open Access
• [Journal Article] γ-SNAP stimulates disassembly of endosomal SNARE complexes and regulates endocytic trafficking pathways. (2015)
  • Author(s): Inoue, H., Matsuzaki, Y., Tanaka, A., Hosoi, K., Ichimura, K., Arasaki, K., Wakana, Y., Asano, K., Tanaka, M., Okuzaki, D., Yamamoto, A., Tani, K. and Tagaya, M.
  • Journal Title: J. Cell Sci. Volume: 128 Pages: 2781-2794
  • DOI: 10.1242/jcs.158634
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] A Role for the Ancient SNARE Syntaxin 17 in Regulating Mitochondrial Division (2015)
  • Author(s): K. Arasaki, H. Shimizu, H. Mogari, N. Nishida, N. Hirota, A. Furuno, Y. Kudo, M. Baba, N. Baba, J. Cheng, T. Fujimoto, N.Ishihara, C. Ortiz-Sandoval, L. Barlow, A Raturi, N. Dohmae, Y. Wakana, H. Inoue, K.Tani, J. Dacks, T.Simmen, M. Tagaya
  • Journal Title: Developmental Cell Volume: 32(9) Issue: 3 Pages: 304-317
  • DOI: 10.1016/j.devcel.2014.12.011
  • Peer Reviewed
• [Journal Article] Valosin-containing protein-interacting membrane protein (VIMP) links the endoplasmic reticulum with microtubules in concert with cytoskeleton-linking membrane protein (CLIMP)-63 (2014)
  • Author(s): Noda, C., Kimura, H., Arasaki, K., Matsushita, M., Yamamoto, A., Wakana, Y., Inoue, H., and Tagaya, M.
  • Journal Title: J. Biol. Chem. Volume: 289 Issue: 35 Pages: 24304-24313
  • DOI: 10.1074/jbc.m114.571372
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Moonlighting functions of the NRZ (mammalian Dsl1) complex. Front (2014)
  • Author(s): Tagaya, M., Arasaki, K., Inoue, H., and Kimura, H.
  • Journal Title: Cell Develop. Biol Volume: (in press) Pages: 25-25
  • DOI: 10.3389/fcell.2014.00025
  • Peer Reviewed / Open Access
• [Presentation] 毛細胆管形成におけるRab11-FIPsの機能 (2015)
  • Author(s): 細井香里，舘野祐太，多賀谷光男，井上弘樹
  • Organizer: 第88回日本生化学会・第38回日本分子生物学会 合同年会
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2015-12-01
• [Presentation] SNAREタンパク質Bet1は浸潤突起へのMT1-MMPの効率的な輸送に必要である (2015)
  • Author(s): 宮川拓也，青木瑶子，渡邉卓也，山口英樹 ，多賀谷光男，井上弘樹
  • Organizer: 第88回日本生化学会・第38回日本分子生物学会 合同年会
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2015-12-01
• [Presentation] g-SNAPはエンドソームSNAREの解離を促進し，初期エンドソームからの小胞輸送に機能する (2014)
  • Author(s): 井上弘樹，松崎友香，田中理華，細井香里，浅野謙一，田中正人，奥崎大介，多賀谷光男
  • Organizer: 第87回日本生化学会年会
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2014-10-15 – 2014-10-18