Identification and analysis of biokinetics of a lysosomal transcription factor that controls the infiltration of oral cancer cells

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K19203
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 57060:Surgical dentistry-related
• Research Institution: Nagasaki University
• Principal Investigator: Hiroshi Sakamoto 長崎大学, 医歯薬学総合研究科(歯学系), 助教 (40836748)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 口腔扁平上皮癌 / リソソーム / 浸潤・転移

Outline of Final Research Achievements

Invasion and metastasis are the major factors that cause cancer cells to kill patients. From our own research, we identified the transcription factor TFEB, which correlates with the invasion of oral squamous cell carcinoma. TFEB functions as a master regulator that controls various lysosomal proteins. The purpose of this study is to clarify the involvement of invasion and metastasis of TFEB found by squamous cell carcinoma using in vitro experiments and in vivo experiments using mice. First, in vitro experiments showed that suppression of TFEB in squamous cell carcinoma cells dramatically reduced invasion. Next, a cancer-bearing mouse model transplanted with nude mice was prepared and the anti-tumor effects were compared. As a result, almost the same results were obtained.

Free Research Field

口腔外科学

Academic Significance and Societal Importance of the Research Achievements

癌細胞が患者の生命を奪う最大の要因は浸潤と転移であるが、この２つを防ぐ有効な治療法は未だない。癌細胞におけるリソソーム性プロテアーゼの分泌量と癌細胞の浸潤・転移には強い相関がある事が報告されており、リソソーム性プロテアーゼは癌細胞が周辺組織を浸潤する際に大量に分泌され、癌転移において重要な役割を果たす。従って、本研究の結果より、リソソームのマスター分子として機能するTFEBを制御すれば、癌細胞の浸潤・転移に予防、診断、治療への幅広い応用が可能である。