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

2016 Fiscal Year Final Research Report

• 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
• 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.

Free Research Field

生化学