Novel theraputic stratagey for lung cancer targeting PKCeta
| Project/Area Number |
17K07226
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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 |
Tumor therapeutics
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| Research Institution | Showa University |
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Principal Investigator |
Ohba Motoi 昭和大学, 大学共同利用機関等の部局等, 講師 (70297018)
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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 |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 肺がん / 分子標的治療薬 / PKC / 分子標的治療 / アポトーシス / 細胞内輸送 |
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| Outline of Final Research Achievements |
Here we present a novel therapeutic strategy for non-small cell lung cancer (NSCLC) targeting protein kinase C η (PKCeta: PKCη). It induces apoptosis and suppresses invasion and metastasis by its gene knockdown in NSCLC cells, especially lung adenocarcinoma cells. First, we discover some small molecule compounds which inhibit PKCη mRNA expression by utilizing a new drug screening system detecting the transcriptional activity of PKCη gene. The drug screening system and these small molecule compounds have been applied as new patent rights. Next, we developed PKCη-specific si/shRNA, dramatically suppressing the PKCη protein expression. These siRNA leads to growth inhibition of NSCLC in vivo. Finally, we found molecular mechanisms of the inhibition of cell proliferation and motility exerted by PKCη-knockdown and identified a downstream molecule of PKCη, which plays a crucial role in NSCLC.
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| Academic Significance and Societal Importance of the Research Achievements |
肺がんは癌死亡率の第１位を占め、罹患率も極めて高く、治療法の確立は喫緊の課題である。本研究は、PKCηを標的とした新規肺癌分子標的治療法の提案である。PKCηは肺がん細胞において、EGFR等の増殖因子受容体や接着因子の膜輸送制御に関与する。本治療戦略はPKCηの機能阻害を介して、上記分子の適切な細胞内輸送を妨げることで、がん細胞の増殖阻害・浸潤・転移能抑制を誘導する新たな視点からの癌治療法である。更に、既存のEGFRチロシンキナーゼ阻害剤における獲得耐性の克服にも応用可能である。また、標的分子の転写活性に着目した本研究独自の大規模薬剤探索法は、新規治療薬の発見・同定につながるものと考える。
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Report
(4 results)
Research Products
(23 results)
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[Journal Article] RAS and EGFR Amplifications Mediate Resistance to Rociletinib and Osimertinib in Acquired Afatinib-Resistant NSCLC Harboring Exon 19 Deletion/T790M in EGFR.2019
Author(s)
Nakatani K, Yamaoka T, Ohba M, Fujita KI, Arata S, Kusumoto S, Taki-Takemoto I, Kamei D, Iwai S, Tsurutani J, Ohmori T.
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Journal Title
Mol Cancer Ther.
Volume: 18
Pages: 112-126
Related Report
Peer Reviewed
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[Journal Article] Blockade of EGFR Activation Promotes TNF-Induced Lung Epithelial Cell Apoptosis and Pulmonary Injury.2019
Author(s)
Yamaoka T, Arata S, Homma M, Homma T, Kusumoto S, Ando K, Manabe R, Kishino Y, Ohba M, Tsurutani J, Takimoto M, Ohmori T, Sagara H.
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Journal Title
Int J Mol Sci.
Volume: 20(16)
Issue: 16
Pages: 4021-4021
DOI
Related Report
Peer Reviewed / Open Access
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