Examination of the mechanism of pancreatic cancer progression through epithelial-mesenchymal transition and its potential as a therapeutic target .
| Project/Area Number |
19K17500
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 53010:Gastroenterology-related
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| Research Institution | Yokohama City University |
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Principal Investigator |
SATO Takeshi 横浜市立大学, 附属病院, 助教 (50806106)
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| Project Period (FY) |
2019-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 膵臓癌 / 上皮間葉転換 |
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| Outline of Research at the Start |
膵癌は増加傾向にある5年生存率が10％に満たない予後不良な疾患である．局所浸潤や転移を起こしやすく，予後不良の原因になっている．これらの性質をもたらす重要な機序として，細胞接着が弱まり，移動能力が高まる上皮間葉転換（EMT）という現象が膵癌細胞では起こりやすいことが挙げられている．EMTを起こした癌細胞は，治療抵抗性が高くなる可能性も示唆されており，細胞接着分子の一つである，E-cadherinはこれらの現象に深く関わっているとされる．動物実験や薬剤によるスクリーニングを行い，EMTやE-cadherinが膵癌において重要な現象・分子であることを示し，新たな治療開発へと繋げることを目的とする．
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| Outline of Final Research Achievements |
Pancreatic cancer is a disease with a poor prognosis with a 5-year survival rate of less than 10%. It is said that epithelial-mesenchymal transition (EMT) is likely to occur in pancreatic cancer cells, which is one of the causes of promote local infiltration and metastasis. We focused on E-cadherin (CDH1): a molecule whose expression is reduced through EMT and is involved in tumor progression. We investigated it in vivo and in vitro. It was suggested that the loss of CDH1 from pancreatic cancer cells increased the infiltration and migration ability of pancreatic cancer cells, which was thought to be a factor to promote malignancy of pancreatic cancer. Loss of CDH1 increased the expression of HDAC1, histone deacetylase. It was shown that inhibition of HDAC1 suppresses the growth of CDH1-depleted pancreatic cancer cells.
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| Academic Significance and Societal Importance of the Research Achievements |
今回の検討で，接着分子の１つであるE-cadherinが，膵癌細胞において浸潤能や移動能を亢進させ，腫瘍進展に促進的に働くことが示唆された．E-cadherinの発現が低下した膵癌においては，ヒストン脱アセチル化酵素（HDAC）の発現が亢進していることが示され，その一つであるHDAC1を阻害することで膵癌細胞の増殖が抑制された．このことは，E-cadherinの発現低下を伴う膵癌において，HDAC阻害剤が治療効果を認める可能性があることを示唆している．
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Report
(3 results)
Research Products
(1 results)
