Elucidation of TRP signal activation mechanism in tumor-stromal seqence in oral tumor and its clinical application

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K17017
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 57020:Oral pathobiological science-related
• Research Institution: Kyushu University
• Principal Investigator: Tajiri Yudai 九州大学, 歯学研究院, 共同研究員 (30820659)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Keywords: 腫瘍実質-間質連関

Outline of Final Research Achievements

The aim of this study was to elucidate the underlying mechanism which can regulate TRPV4 signals abnormally activated by the extracellular environment in oral squamous cell carcinoma (OSCC). In our established experimental setting to activate YAP signaling, it was not confirmed that TRPV4 signal expression was regulated by YAP signaling.
On the other hand, gene expression in OSCC pathological specimens was comprehensively investigated using DNA microarray method. The results suggested that p63 expression increases during the carcinogenesis process, and MAPK is activated in the invasive carcinomalesion. Furthermore, together with the research using OSCC cell lines, it is suggested that a novel oncogene ARL4C is cooperatively regulated by p63 and MEK/ERK-MAPK in OSCCs.

Free Research Field

口腔病理学

Academic Significance and Societal Importance of the Research Achievements

悪性腫瘍では遺伝子異常が生じるため、細胞が自律的に増殖する。本邦では、病変組織を用いて遺伝子異常を明らかにすることで、患者一人一人に適した治療法を提供できるがんゲノム医療の普及が進められている。一方、口腔癌の90%以上を占める OSCCにおける特異的な遺伝子異常が少ないため、異常活性化した細胞内シグナルが発癌に寄与すると予想される。本研究では、OSCC病理標本(非腫瘍部、上皮性異形成/上皮内癌、浸潤癌を含む)における遺伝子発現について、網羅的に検討した。本研究結果によってOSCCの発癌過程において活性化するシグナルが明らかとなった。この学術意義は高く、治療への応用の足掛かりとなる。