Identification of driver genes in lung cancer through a semi-genome wide shRNA library screen based on anoikis resistance phenotype

2016 Fiscal Year Final Research Report

• Project/Area Number: 26293197
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Nagoya University
• Principal Investigator: Sato Mitsuo 名古屋大学, 医学部附属病院, 講師 (70467281)
• Co-Investigator(Kenkyū-buntansha): 近藤 征史 名古屋大学, 医学(系)研究科(研究院), 准教授 (00378077) ; 長谷 哲成 名古屋大学, 医学部附属病院, 助教 (30621635)
• Co-Investigator(Renkei-kenkyūsha): YUKAWA Hiroshi 名古屋大学, 大学院工学系研究科, 特任講師 (30634646) ; YOKOI Kohei 名古屋大学, 大学院医学系研究科, 教授 (60378007)
• Research Collaborator: YOGO Naoyuki 名古屋大学, 大学院工学研究科, 研究員 (70817874)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 肺癌 / アノイキス / プールshRNAライブラリー / プロテアソーム

Outline of Final Research Achievements

This study was aimed to identify novel therapeutic targets for lung cancer. To this end, we employed two approached. First, we tried to identify genes that contribute to anoikis resistance by doing shRNA library screen using an immortalized normal human bronchial epithelial cell line, HBEC. Anoikis is a special type of apoptosis induced by loss of attachment to extra cellular matrix, and resistance against anoikis is one of critical malignant properties of cancer cells. We identified RNF146 as a gene whose loss could contribute to anoikis resistance in HBEC. However, this result was not reproduced in lung cancer cell lines. Second, we did an integrated analysis combining a shRNA library screen with utilization of gene expression and copy number analysis using an aggressive lung cancer cell line, H460. We identified proteasome subunit gene PSMA6 as a novel therapeutic target for lung cancer.

Free Research Field

肺癌

Academic Significance and Societal Importance of the Research Achievements

肺癌は難治癌の代表であり、新しい有効な治療方法の開発は社会的に重要な課題である。本研究は肺癌の新規治療標的の発見を目的とした。肺癌細胞株を用いて、プールshRNAライブラリーによる網羅的ノックダウン手法を用いた機能的なスクリーニングと肺癌における遺伝子発現量およびコピー数の統合解析を実施した。その結果、肺癌の新規治療標的としてプロテアソームサブユニット遺伝子PSMA6を同定し、結果を論文発表した。