A novel therapeutic strategy targeted the conformational plasticity of a single molecule for cancer cell invasion and metastasis

• Project/Area Number: 15K15084
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Pathological medical chemistry
• Research Institution: The University of Tokushima
• Principal Investigator: SASAKI Takuya 徳島大学, 大学院医歯薬学研究部(医学系), 教授 (40241278)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: がん浸潤・転移 / 集団的浸潤 / Rab13 / JRAB / 構造変化

Outline of Final Research Achievements

We generated a structural model of JRAB/MICAL-L2 through a combination of bioinformatic and biochemical analyses and thereby revealed how JRAB/MICAL-L2 interplays with Rab13 and how its conformational change occurs. In addition, we elucidated that the conformational plasticity in JRAB/MICAL-L2 causes spatiotemporal actin cytoskeletal rearrangement to control direction and speed of cell movement and traction force of the cell population through a robust approach combining cell biology, live imaging, computational biology, and biomechanics. Moreover, we showed that JRAB/MICAL-L2 conformational plasticity is necessary for migration of cell group under 3D environment. These findings suggest that the conformational plasticity of JRAB/MICAL-L2 generates ‘low and order’ in the cancer cell invasion. Thus, our multidisciplinary approach will bring a novel therapeutic strategy targeted the conformational plasticity of a single molecule for cancer cell invasion and metastasis.

Research Products

• [Journal Article] Conformational Plasticity of JRAB/MICAL-L2 Provides 'Law and Order' (2016)
  • Author(s): A. Sakane, S. Yoshizawa, M. Nishimura, Y. Tsuchiya, N. Matsushita, K. Miyake, K. Horikawa, I. Imoto, C. Mizuguchi, H. Saito, T. Ueno, S. Matsushita, H. Haga, S. Deguchi, K. Mizuguchi, H.
  • Journal Title: Molecular Biology of the Cell Volume: 27 Issue: 20 Pages: 3095-3108
  • DOI: 10.1091/mbc.e16-05-0332
  • Peer Reviewed / Open Access
• [Journal Article] Roles of Rab family small G proteins in formation of the apical junctional complex in epithelial cells (2015)
  • Author(s): Sakane, A. and Sasaki, T.
  • Journal Title: Cell Polarity: Biological Role and Basic Mechanisms Volume: 1 Pages: 349-374
  • DOI: 10.1007/978-3-319-14463-4_15
  • ISBN: 9783319144627, 9783319144634