Examination of the mechanism of pancreatic cancer progression through epithelial-mesenchymal transition and its potential as a therapeutic target .

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K17500
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Yokohama City University
• Principal Investigator: SATO Takeshi 横浜市立大学, 附属病院, 助教 (50806106)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: 膵臓癌 / 上皮間葉転換

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.

Free Research Field

膵臓癌

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．