The function of p130 Cas on the epithelial-mesenchymal transition in oral squamous cell carcinoma

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K11884
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Surgical dentistry
• Research Institution: Kyushu Dental College
• Principal Investigator: Yoshioka Izumi 九州歯科大学, 歯学部, 教授 (10305823)
• Co-Investigator(Kenkyū-buntansha): 松原 琢磨 九州歯科大学, 歯学部, 准教授 (00423137) ; 古株 彰一郎 九州歯科大学, 歯学部, 教授 (30448899) ; 自見 英治郎 九州大学, 歯学研究院, 教授 (40276598) ; 松尾 拡 九州歯科大学, 歯学部, 教授 (70238971) ; 大澤 賢次 九州歯科大学, 歯学部, 助教 (70638238)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 口腔扁平上皮がん / 上皮間葉移行 / p130Cas / 骨浸潤

Outline of Final Research Achievements

TGF-β is abundantly expressed in the bone matrix and is involved in the acquisition of aggressiveness by tumors. TGF-β is also important to cytoskeletal changes during tumor progression. TGF-β induced the phosphorilaion of Smad3 and p130Cas as well as epithelial-mesenchymal transition (EMT) accompanied by the downregulation of the expression of E-cadherinand the upregulation of the expression of N-cadherin, or Snail. SB431542, a specific inhibitor of Smad2/3 signaling, abrogated the TGF-β-induced phosphorylation of p130Cas and morphological changes. Silencing p130Cas using an shRNA or siRNA in SCCVII cells suppressed TGF-β-induced cell migration, invasion, EMT, and matrix metalloproteinase-9 (MMP-9) production. Compared with control SCCVII cells, SCCVII cells with silenced p130Cas strongly suppressed zygomatic and mandibular destruction in vivo.

Free Research Field

口腔外科学、口腔内科学

Academic Significance and Societal Importance of the Research Achievements

本研究ではTGF-βが誘導するがん細胞の上皮間葉移行（EMT）や骨浸潤をTGF-βの下流でp130Casが制御していることを証明した。EMTは上皮性のがん細胞がより運動性の高い間葉系細胞の表現系を獲得し、転移しやすくなった状態である。また、EMTを起こした細胞はapoptosisに抵抗性になることも報告されており、TGF-β-p130Casは口腔扁平上皮がんの骨浸潤の新しい治療法のターゲットになり得るかもしれない。