Investigation of the mechanism of oral squamous cell carcinoma tumorigenesis through PIEZO1

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K18966
• 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: Hasegawa Kana 九州大学, 歯学研究院, 助教 (30793989)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: 口腔扁平上皮癌 / PIEZO1 / Hippoシグナル

Outline of Final Research Achievements

In this study, we examined the interaction of Hippo pathway and PIEZO1 in oral squamous cell carcinoma (OSCC) and the function of Hippo pathway on the tumorigenesis in OSCC.　It was found that YAP signal controlled PIEZO1 expression in suspension culture in OSCC cell lines. Knockdown of PIEZO1 by siRNA reduced PIEZO1 agonist-dependent Ca2+ influx, ERK1/2 activation, and OSCC cellular growth. Immunohistochemical analyses were showed that YAP was expressed in the nucleus in tumor lesions in OSCC specimens, and YAP in the nucleus was detected in tumor lesions with frequent expression of both PIEZO1 and Ki-67 in OSCC specimens.
These results suggest that the YAP/PIEZO1 axis promotes OSCC cell proliferation.

Free Research Field

口腔病理

Academic Significance and Societal Importance of the Research Achievements

OSCCでは、他の癌腫において治療標的となる遺伝子異常が少ないことが報告されている。そのため、治療標的となる異常に活性化した細胞内シグナル伝達の同定はOSCCの新規の治療法の開発に繋がることが期待される。本研究はYAPシグナルがOSCCにおいて異常に活性化し、PIEZO1の発現を介して、OSCCの細胞増殖を制御することを明らかにした。本研究の成果はCaイオンチャネルを介した異常なシグナル伝達の活性化は口腔扁平上皮癌の新たな治療標的となりうる可能性を示した。