Analysis of the role of histone deacetylase 1 in distant metastasis of pancreatic ductal cancer

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K18113
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Osaka University
• Principal Investigator: Yamamoto Kei 大阪大学, 医学部附属病院, 医員 (90835240)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: 上皮間葉転換 / HDAC1 / SNAIL

Outline of Final Research Achievements

Pancreatic cancer causes cancer infiltration and metastasis through epithelial-mesenchymal transition. In this study, we revealed that one of the epigenetic mechanisms, histone deacetylase 1 (HDAC1), promotes distant metastasis via EMT in pancreatic cancer. Furthermore, it was shown that Virinostat, an HDAC1 inhibitor, regulates EMT by suppressing SNAIL, which is an EMT-related transcription factor.

Free Research Field

腫瘍免疫

Academic Significance and Societal Importance of the Research Achievements

浸潤性膵管癌は極めて予後不良であり、新たな治療標的の同定は喫緊の課題である。本研究では膵癌においてHDAC1及びSNAILがEMTを介して遠隔転移を制御し、HDAC1が膵癌治療における新たな治療ターゲットとなり得る事を示した。癌発生学的に類似している胆道癌においても同遺伝子が特定されており、難治性癌である膵胆道癌においてEMTを制御する重要なエピジェネティック機構の一つが明らかとなった。