The analysis of interface connecting cell adhesion and cytoskeleton on epithelial tissue architecture
| Project/Area Number |
15K08158
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
General anatomy (including histology/embryology)
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| Research Institution | Dokkyo Medical University |
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Principal Investigator |
Itoh Masahiko 獨協医科大学, 医学部, 准教授 (70270486)
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| Project Period (FY) |
2015-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Keywords | 細胞接着 / 細胞骨格 / 癌転移 / 糸球体上皮 / ZO-1 / ZO-2 / ARHGEF11 / 上皮 / 癌細胞転移 / EMT / E-cadherin / タイトジャンクション / 腎糸球体上皮 / 上皮細胞 / 腫瘍形成 / スプライシング |
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| Outline of Final Research Achievements |
In the current research, we found that ARHGEF11 isoform containing exon38, which does not exhibit binding ability to ZO-1, is expressed in metastatic breast cancer cells, while the isoform without exon38 is expressed in non-metastatic cells. When ARHGEF11 isoform is inactivated in metastatic breast cancer cells, invasion ability of the cells is reduced and fibroblastic morphology changes. Furthermore, tumor formation in vivo is suppressed. These data indicate that the splicing shift of ARHGEF11 is implicated in the metastatic progression of breast cancer.
As a separate project, we established mice deficient for ZO-2 in podocytes. Our previous study demonstrated that the loss of ZO-1 leads to proteinuria, however, ZO-2 deficient mouse does not exhibit similar abnormalities. On the other hand, when both molecules are inactivated, degeneration of podocytes and proteinuria is deteriorated than ZO-1 deficiency. Therefore, ZO-2 is considered to play supportive role for ZO-1 in podocytes.
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| Academic Significance and Societal Importance of the Research Achievements |
細胞接着・細胞骨格が変化する際の分子機構については、構成分子の発現を調べることで論じられることが多かった。しかし、インターフェース分子のsplicing変化が上皮細胞の表現系転換に関与するという本研究の知見は、発現レベルのみならずsplicing解析も重要であることを示している。また、splicing patternが癌の進行度合いを予測する診断マーカーとなりうる可能性も提示するものである。
一方、従来ZO-1とZO-2は相補的とされ、疾患解析等においてはZO-1のみを分析する事例が多かった。本研究は、これら分子の働きは臓器によって異なりZO-2についても解析を行う必要性あることを示唆している。
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Report
(6 results)
Research Products
(10 results)
