A study on the mechanism of invasion and metastasis thorough epithelial-mesenchymal transition in oral squamous cel carcinoma

• Project/Area Number: 26463014
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Surgical dentistry
• Research Institution: Kyushu University
• Principal Investigator: Kawano Shintaro 九州大学, 大学病院, 講師 (00398067)
• Co-Investigator(Kenkyū-buntansha): 豊嶋 健史 九州大学, 歯学研究院, 共同研究員 (20546569) ; 中村 誠司 九州大学, 歯学研究院, 教授 (60189040)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 浸潤 / 転移 / 口腔癌 / 上皮間葉転換 / ZEB1 / ZEB2 / deltaNp63 / 口腔扁平上皮癌 / ZEBファミリー / ΔNp63 / miR205 / 上皮-間葉転換

Outline of Final Research Achievements

Previously, microRNA (miR) microarray analyses were performed to identify the responsible gene for epithelial-mesenchymal transition ( EMT）mediated by ΔNp63β in oral squamous cell carcinoma (OSCC). As the results, we focused on miR-205 that is up-regulated by ΔNp63β-forced expression. The inhibitor for miR-205 was thus added into the culture supernatant of OSCC cells strongly expressingΔNp63β. And then, expression of zinc finger E-box binding homeobox (ZEB)1 and ZEB2 was up-regulated, epithelial markers including cytokeratin 19 and E-cadherin were also down-regulated, mesenchymal markers were up-regulated. Furthermore, capacities of invasion and migration were enhanced by the treatment of inhibitor for miR-205. These results showed tumor-suppressive roles of ΔNp63β and miR-205 by inhibiting EMT thorough modulating ZEB1 and ZEB2 expressions in OSCC.

Research Products

• [Journal Article] Critical roles of Wnt5a-Ror2 signaling in aggressiveness of oral squamous cell carcinoma and production of matrix metalloproteinase-2 via ΔNp63β-mediated epithelial-mesenchymal transition (2017)
  • Author(s): Taiki Sakamoto, Shintaro Kawano, Ryota Matsubara, Yuichi Goto, Teppei Jinno, Yasuyuki Maruse, Naoki Kaneko, Yuma Hashiguchi, Taichi Hattori, Shoichi Tanaka, Ryoji Kitamura, Tamotsu Kiyoshima, Seiji Nakamura,
  • Journal Title: Oral Oncology Volume: 69 Pages: 15-25
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Clinicopathological evaluation of pre-operative chemoradiotherapy with S-1 as a treatment for locally advanced oral squamous cell carcinoma (2016)
  • Author(s): Kawano S, Zheng Y, Oobu K, Matsubara R, Goto Y, Chikui T, Yoshitake T, Kiyoshima T, Jinno T, Maruse Y, Mitate E, Kitamura R, Tanaka H, Toyoshima T, Sugiura T, Nakamura S
  • Journal Title: Oncology letters Volume: 11 Pages: 3369-3376
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Increased expression of interleukin-6 predicts poor response to chemoradiotherapy and unfavorable prognosis in oral squamous cell carcinoma. (2015)
  • Author(s): Jinno T, Kawano S, Maruse Y, Matsubara R, Goto Y, Sakamoto T, Hashiguchi Y, Kaneko N, Tanaka H, Kitamura R, Toyoshima T, Jinno A, Moriyama M, Oobu K, Kiyoshima T, Nakamura S.
  • Journal Title: Oncol Rep Volume: 33 Issue: 5 Pages: 2161-2168
  • DOI: 10.3892/or.2015.3838
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] A case of mucoepidermoid carcinoma of the sublingual gland accompanied with extensive dystrophic calcification and intratumoral bone formation. (2015)
  • Author(s): Maruse Y, Kawano S, Kiyoshima T, Goto Y, Matsubara R, Chikui T, Yoshiga D, Nakamura S.
  • Journal Title: Head and Neck Volume: 印刷中 Issue: 11 Pages: E161-E164
  • DOI: 10.1002/hed.24036
  • Peer Reviewed / Open Access
• [Presentation] 口腔扁平上皮癌におけるkallikrein related peptidase 6の発現と機能に関する研究 (2017)
  • Author(s): 金子直樹、川野真太郎、松原良太、後藤雄一、神野哲平、丸瀬靖之、坂本泰基、橋口有真、松村万由、服部多市、田中秀明、大部一成、中村誠司
  • Organizer: 第35回日本口腔腫瘍学会総会・学術大会
  • Place of Presentation: 福岡市
  • Year and Date: 2017-01-26
• [Presentation] 口腔扁平上皮癌におけるmiR-205の発現と機能に関する研究～特にΔNp63との関連について～ (2016)
  • Author(s): 橋口有真、川野真太郎、後藤雄一、松原良太、神野哲平、丸瀬靖之、金子直樹、坂本泰基、松村万由、中村誠司
  • Organizer: 第70回日本口腔科学会学術集会
  • Place of Presentation: 福岡市
  • Year and Date: 2016-04-15
• [Presentation] 口腔扁平上皮癌の遊走能におけるΔNp63を介したWnt5a-Ror2シグナル経路の関与 (2016)
  • Author(s): 坂本泰基、川野真太郎、松原良太、後藤雄一、神野哲平、丸瀬靖之、金子直樹、橋口有真、中村誠司
  • Organizer: 第70回日本口腔科学会学術集会
  • Place of Presentation: 福岡市
  • Year and Date: 2016-04-15
• [Presentation] 口腔扁平上皮癌におけるkallikrein related peptidase 6の発現と機能に関する研究 (2016)
  • Author(s): 金子直樹、川野真太郎、松原良太、後藤雄一、神野哲平、丸瀬靖之、坂本泰基、橋口有真、松村万由、中村誠司
  • Organizer: 第70回日本口腔科学会学術集会
  • Place of Presentation: 福岡市
  • Year and Date: 2016-04-15
• [Presentation] 口腔扁平上皮癌におけるΔNp63を介した浸潤・転移の分子機構に関する研究～Wnt5a-Ror2シグナル経路との関連～ (2016)
  • Author(s): 坂本泰基、川野真太郎、松原良太、後藤雄一、神野哲平、丸瀬靖之、金子直樹、橋口有真、大部一成、中村誠司
  • Organizer: 第3４回日本口腔腫瘍学会総会・学術大会
  • Place of Presentation: 横浜市
  • Year and Date: 2016-01-21
• [Presentation] PD-1/PD-L1 coexpression is associated with poor prognosis in the oral squamous cell carcinoma patients (2015)
  • Author(s): Y. Maruse, S. Kawano, R. Matsubara, Y. Goto, T. Jinno, N. Kaneko, T. Sakamoto, Y. Hashiguchi, K. Oobu, S. Nakamura
  • Organizer: 第63回国際歯科研究学会（JADR）総会・学術大会
  • Place of Presentation: 福岡市
  • Year and Date: 2015-10-30
  • Int'l Joint Research
• [Presentation] A study on the expression and function of interleukin-6 in oral squamous cell carcinoma ～its possible involvement in chemotherapeutic resistance～ (2015)
  • Author(s): T. Jinno, S. Kawano, R. Matsubara,Y. Maruse, T. Sakamoto, Y. Hashiguchi, N. Kaneko, A. Jinno, M. Morioka, K. Oobu, T. Kiyoshima, S. Nakamura.
  • Organizer: 第39回日本頭頸部癌学会 第4回アジア頭頸部癌学会
  • Place of Presentation: 神戸市
  • Year and Date: 2015-06-03
  • Int'l Joint Research
• [Presentation] Clinicopathological evaluation of preoperative chemoradiotherapy with S-1 for locally advanced OSCC (2015)
  • Author(s): Y. Hashiguchi, S. Kawano, K. Oobu, R. Matsubara, Y. Goto, T. Jinno, Y. Maruse, T. Sakamoto, N. Kaneko, M. Morioka, S. Nakamura.
  • Organizer: 第39回日本頭頸部癌学会 第4回アジア頭頸部癌学会
  • Place of Presentation: 神戸市
  • Year and Date: 2015-06-03
  • Int'l Joint Research
• [Presentation] 根治的頸部郭清術 (2015)
  • Author(s): 川野 真太郎
  • Organizer: 第33回日本口腔腫瘍学会総会・学術大会
  • Place of Presentation: 奈良市
  • Year and Date: 2015-01-29 – 2015-01-30
  • Invited
• [Remarks] 九州大学大学院歯学研究院口腔顎顔面病態学講座顎顔面腫瘍制御学分野
  • URL: http://www.omfs1.dent.kyushu-u.ac.jp
• [Remarks] 九州大学大学院歯学研究院 顎顔面腫瘍制御学分野ホームページ
  • URL: http://www.omfs1.dent.kyushu-u.ac.jp
• [Remarks] 九州大学 研究者情報
  • URL: http://hyoka.ofc.kyushu-u.ac.jp/search/details/K002902/research.html