Clarification of precondition causing direct reprogramming in lung cancer

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K09676
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Dokkyo Medical University
• Principal Investigator: Yazawa-Sato Hanako (佐藤) 獨協医科大学, 医学部, 講師 (60438132)
• Co-Investigator(Kenkyū-buntansha): 原 由紀子 (宍戸) 京都府立医科大学, 医学(系)研究科(研究院), 准教授 (40313267) ; 矢澤 卓也 獨協医科大学, 医学部, 教授 (50251054) ; 宮田 千恵 聖マリアンナ医科大学, 医学部, その他(移行) (20613847)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 肺癌 / リプログラミング

Outline of Final Research Achievements

The purpose of this study was to examine indispensable condition for direct reprogramming in lung adenocarcinoma cells. We established RB1/TP53-knockout lung adenocarcinoma cells by CRISPR-Cas9 method and performed gene expression analysis. It was clarified that various epithelial-mesenchymal transition-related molecules are upregulated in RB1/TP53-knockout lung adenocarcinoma cells. Next, we tried to transfect POU3F4/POU4F2 genes, which are associated with neural differentiation, in RB1/TP53-knockout lung adenocarcinoma cells. However, neuroendocrine differentiation was not induced in the cells. Finally, we established lung adenocarcinoma cells expressing CDX2, a transcription factor (TF) promoting intestinal differentiation, or SALL4, a TF promoting enteroblastic differentiation, to examine the association in tumorigenesis of lung adenocarcinomas of intestinal type or hepatoid type. We obtained evidence that intestinal phenotype is induced by CDX2 in lung adenocarcinoma cells.

Free Research Field

肺癌細胞の分化とリプログラミング機構

Academic Significance and Societal Importance of the Research Achievements

肺癌は本邦においても世界的に見ても最も予後不良な癌腫であり、増加の一途を辿っている。その中でも肺腺癌は肺癌の中でも最も多い組織型であるとともに、肺腺癌細胞が有する細胞分化形質は多岐にわたっており、そのことが効果的な治療薬の開発を困難にしている。本研究で得られた知見及び本研究の更なる推進により肺腺癌の分化メカニズムや形質転換メカニズムが明らかになり、得られた知見は将来、効果的な治療薬の開発に繋がるものと思われる。