| Project/Area Number |
15K15084
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Pathological medical chemistry
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| Research Institution | The University of Tokushima |
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Principal Investigator |
SASAKI Takuya 徳島大学, 大学院医歯薬学研究部(医学系), 教授 (40241278)
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| Project Period (FY) |
2015-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥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)
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| Keywords | がん浸潤・転移 / 集団的浸潤 / Rab13 / JRAB / 構造変化 |
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| 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.
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