Novel cancer therapeutic target, epithelial membrane protein 1 (EMP1), investigation of the molecular mechanism inducing invasion and metastasis
| Project/Area Number |
17K08657
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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 |
Pathological medical chemistry
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| Research Institution | Shiga University of Medical Science |
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Principal Investigator |
Akio Shimizu 滋賀医科大学, 医学部, 助教 (30769279)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | がん / 浸潤 / 転移 / EMP1 / がん転移 / Copine-III / Rac1 / 細胞運動 / 浸潤・転移 / 細胞間相互作用 |
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| Outline of Final Research Achievements |
Metastatic cancer is frequently led to fatality. Thus, understanding of the underlying mechanism is important to reduce it. The expression of epithelial membrane protein 1 (EMP1) was upregulated in prostate cancer cells by contacting with surrounding stroma cells. EMP1 has four transmembrane domains. Overexpression of EMP1 in prostate cancer, LNCaP cells (EMP1-LNCaP cells) enhanced invasiveness, which was also observed in other types of cancer cells. In in vivo analysis, EMP1-LNCaP cells implanted in the prostate metastasized to lymph nodes and the lung but the parental LNCaP did not. Next, copine-III was identified by usage of tandem mass spectrometry as a novel molecule binding to the intracellular region of EMP1. The EMP1-copine-III complex induced the signal via Src, Vav2, and Rac1, leading to the enhanced cancer cell migration and invasion. As clinical implications, increased EMP1 expression was observed in the samples from prostate cancer patients with higher Gleason scores.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究は、がん細胞と正常細胞の相互作用によってEMP1の発現が上昇することを明らかにし、浸潤・転移への寄与を明らかにした点に新規の学術的意義がある。EMP1は悪性度の高いがん患者検体においてその発現が上昇していたことを明らかにしたが、EMP1は細胞膜タンパク質であり、外部から抗体や薬剤などでその作用を阻害しやすいことは臨床応用へ進む上で大きな利点である。本研究の成果から、がんの治療標的あるいは分子マーカーとしてEMP1 は有用である可能性が示された。
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Report
(4 results)
Research Products
(17 results)
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[Journal Article] Identification of transmembrane protein 168 mutation in familial Brugada syndrome.2020
Author(s)
Shimizu A, Zankov DP, Sato A, Komeno M, Toyoda F, Yamazaki S, Makita T, Noda T, Ikawa M, Asano Y, Miyashita Y, Takashima S, Morita H, Ishikawa T, Makita N, Hitosugi M, Matsuura H, Ohno S, Horie M, Ogita H.
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Journal Title
FASEB Journal
Volume: 34
Issue: 5
Pages: 6399-6417
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Mutant KCNJ3 and KCNJ5 potassium channels as novel molecular targets in bradyarrhythmias and atrial fibrillation.2019
Author(s)
Yamada N, Asano Y, Fujita M, Yamazaki S, Inanobe A, Matsuura N, Kobayashi H, Ohno S, Ebana Y, Tsukamoto O, Ishino S, Takuwa A, Kioka H, Yamashita T, Hashimoto N, Zankov DP, Shimizu A, Asakura M, Asanuma H, Kato H, Nishida Y, Miyashita Y, Shinomiya H, Naiki N, Hayashi K, Makiyama T, Ogita H, et al.
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Journal Title
Circulation
Volume: In press
Issue: 18
Pages: 2157-2169
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Epithelial membrane protein 1 promotes tumor metastasis by enhancing cell migration via copine-III and Rac12018
Author(s)
Ahmat Amin MKB, Shimizu A, Zankov DP, Sato A, Kurita S, Ito M, Maeda T, Yoshida T, Sakaue T, Higashiyama S, Kawauchi A, Ogita H.
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Journal Title
Oncogene
Volume: 37
Issue: 40
Pages: 5416-5434
DOI
Related Report
Peer Reviewed / Open Access
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