Targeting for sphingosine kinase in oral squamous cell carcinoma based on omics analysis

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K10111
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 57060:Surgical dentistry-related
• Research Institution: Osaka University
• Principal Investigator: Hamada Masakazu 大阪大学, 大学院歯学研究科, 助教 (80506361)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: オートファジー / 分子標的治療 / Sphingosine kinase / 口腔癌

Outline of Final Research Achievements

Analysis of the TCGA database revealed that CERS5, PLPP3, SGPP1, SPNS3, and S1PT4 as genes related to “Sphingosine” showed differences between primary tumor and solid tissue normal and were also associated with prognosis of head and neck squamous cell carcinoma. Furthermore, treatment of oral squamous cell carcinoma (OSCC) cells with PF-543, a Sphk1 inhibitor, revealed that the NOD-like receptor signaling pathway and necroptosis are common pathways for necrosis, autophagy, and apoptosis, which are cell death in vivo. Further mechanistic and omics data analysis will lead to molecular targeted therapy for OSCC.

Free Research Field

口腔外科全般、口腔癌、分子標的治療

Academic Significance and Societal Importance of the Research Achievements

TCGAデータベースの解析より、『Sphingosine』に関連する遺伝子としてCERS5、PLPP3、SGPP1、SPNS3、S1PT4が腫瘍組織と正常組織で差を認め、予後とも関連していた。さらに、ヒト口腔扁平上皮癌細胞をSphK1阻害薬であるPF-543で処理すると、ネクローシス、アポトーシスならびにオートファジーが誘導され、共通する経路はNOD-like receptor signaling pathwayとNecroptosisであった。今後、これらのメカニズムの解明を通して，副作用の少ないより効率的なSphKをターゲットとした分子標的治療のさらなる発展が期待出来る。