Establishment of anti-invasive and metastasis therapy focusing on Hippo pathway activation by cell adhesion of oral squamous cell carcinoma

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K17237
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 57060:Surgical dentistry-related
• Research Institution: Iwate Medical University
• Principal Investigator: SAITO DAISHI 岩手医科大学, 歯学部, 研究員 (40805876)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: HSC-4 / EMT / catherin switch / Hippo経路 / YAP/TAZ / E-cadherin / N-cadherin

Outline of Final Research Achievements

In human oral squamous cell carcinoma cell HSC-4 cell, YAP/TAZ, which was the effector molecule and transcriptional co-factor in the Hippo signaling pathway, were activated by the disruption of E-cadherin-mediated cell-to-cell contact under the low cell-density condition. The cadherin switch which was an expression change of cadherin from E-cadherin to N-cadherin was induced by activation of YAP/TAZ promoting a nuclear translocation of Slug which was the epithelial-mesenchymal transition-related transcription factor. These results indicated that the mechanism of epithelial-mesenchymal transition which involved in the malignant transformation of the human oral squamous cell carcinoma cell participated in the Hippo signaling pathway.

Free Research Field

口腔外科学分野

Academic Significance and Societal Importance of the Research Achievements

癌細胞の悪性化において、上皮間葉転換によって誘導される細胞間接着因子としてのcadherinの質的・量的変化であるcadherin switchが重要であることが知られている。我々はこの”cadherin switch”を誘導する細胞間接着因子を介したHippo経路の活性化に伴うEMT制御機構の一部を明らかにした。これらの機構は、口腔癌細胞の浸潤・転移を抑制する新規治療戦略樹立のための新たなる基盤となると考えられる。