Development of therapeutics for lung cancer that target factors stabilizing epithelial-to-mesenchymal transition

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K22617
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 53:Organ-based internal medicine and related fields
• Research Institution: Nagoya University
• Principal Investigator: Sato Mitsuo 名古屋大学, 医学系研究科(保健), 教授 (70467281)
• Co-Investigator(Kenkyū-buntansha): 長谷 哲成 名古屋大学, 医学部附属病院, 助教 (30621635) ; 湯川 博 名古屋大学, 未来社会創造機構, 招へい教員 (30634646) ; 田中 一大 名古屋大学, 医学部附属病院, 病院助教 (40809810) ; 川井 久美 名古屋大学, 医学系研究科(保健), 准教授 (50362231) ; 川口 晃司 名古屋大学, 医学部附属病院, 病院准教授 (10402611)
• Project Period (FY): 2019-06-28 – 2022-03-31
• Keywords: 上皮間葉細胞転換 / 肺癌

Outline of Final Research Achievements

Epithelial to mesenchymal transition (EMT) is a phenomenon where cancer cells convert from the epithelial to the mesenchymal cells, leading to enhanced the malignancy. The purpose of this study was to elucidate the role of the GRHL2 gene, which is known as an EMT inhibitor and stabilizer. GRHL2 expression correlates with the epithelial properties of lung cancer cells and is highly expressed in tumor tissues of adenocarcinoma and squamous cell carcinoma compared to normal lung tissue. GRHL2 knockdown by RNA interference in lung cancer cell lines and immortalized normal bronchial epithelial cell lines resulted in promotion and suppression of proliferation. These results suggest that GRHL2 functions as an EMT inhibitor but also has a cancer-promoting effect.

Free Research Field

肺癌

Academic Significance and Societal Importance of the Research Achievements

上皮間葉細胞転換（epithelial to mesenchymal transition, EMT）は癌細胞が上皮系から間葉系へ転換し悪性度を増強する現象である。EMTの制御による癌治療の実現にはEMTのさらなる機序解明が必要である。本課題はEMT抑制遺伝子として知られるGRHL2がEMT抑制因子として機能するにもかかわらず癌促進的な作用も併せ持つことを示した。EMTの機序解明における新たな知見を提供した。