A study on epithelial-mesenchymal transition mediated by deltaNp63 in invasion and metastasis of oral squamous cell carcinoma

• Project/Area Number: 23792358
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Surgical dentistry
• Research Institution: Kyushu University
• Principal Investigator: KAWANO Shintaro 九州大学, 大学病院, 講師 (00398067)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 上皮間葉転換 / 口腔扁平上皮癌 / deltaNp63 / 浸潤 / 転移 / 上皮-間葉転換 / ΔNp63 / 癌幹細胞 / ⊿Np63 / delta p63

Research Abstract

In this study, we investigated the role of deltaNp63 in EMT during progression of oral squamous cell carcinoma (OSCC). The expressions of deltaNp63 and epithelial markers was detected in the OSCC cells, but not in SQUU-B cells (high metastatic potential). Mesenchymal markers were strongly expressed in the SQUU-B cells. Knockdown of endogenous deltaNp63 in HSC-2 cells induced morphological changes to the spindle shape, decreased the expression of epithelial markers, increased the expression of mesenchymal markers, increased migration. By contrast, SQUU-B cells overexpressing deltaNp63 showed changed their morphology from stromal cell-like to epithelial cells. Immunohistochemical staining revealed decreased intensity of deltaNp63 was positively associated with metastases and poor prognosis in the OSCC patients. These results indicated that deltaNp63 downregulation in cancer cells induces a mesenchymal phenotype that is related to tumor progression of OSCC.

Research Products

• [Journal Article] Possible involvement ofΔNp63 downregulation in the invasion and metastasis of oral squamous cell carcinoma via induction of a mesenchymal phenotype (2014)
  • Author(s): Y. Goto, S. Kawano, R. Matsubara, T. Kiyosue, M. Hirano, T. Jinno, Y. Maruse, T. Toyoshima, R. Kitamura, H. Tanaka, K. Oobu, S. Nakamura
  • Journal Title: Clinical & Experimental Metastasis Volume: 214 Pages: 289-306
• [Journal Article] Possible involvement of ΔNp63 downregulation in the invasion and metastasis of oral squamous cell carcinoma via induction of a mesenchymal phenotype (2014)
  • Author(s): Yuichi Goto, Shintaro Kawano, Ryota Matsubara, Takahiro Kiyosue, Mitsuhiro Hirano, Teppei Jinno, Yasuyuki Maruse, Toyoshima Takeshi, Ryoji Kitamura, Hideaki Tanaka, Kazunari Oobu, Seiji Nakamura
  • Journal Title: Clinical & Experimental Metastasis Volume: 214 Issue: 3 Pages: 289-306
  • DOI: 10.1007/s10585-013-9628-z
  • Peer Reviewed / Open Access
• [Journal Article] Immunohistochemical localization of p75 neurotrophin receptor (p75NTR) in oral leukoplakia and oral squamous cell carcinoma (2013)
  • Author(s): Takahiro Kiyosue, Shintaro Kawano, Ryota Matsubara, Yuichi Goto, Mitsuhiro Hirano, Teppei Jinnno, Takeshi Toyoshima, Ryoji Kitamura, Kazunari Oobu, Seiji Nakamura
  • Journal Title: International Journal of Clinical Oncology Volume: 18 Issue: 1 Pages: 154-163
  • DOI: 10.1007/s10147-011-0358-4
  • Peer Reviewed
• [Journal Article] Anti-apoptotic role of the sonic hedgehog signaling pathway in the proliferation of ameloblastoma. (2013)
  • Author(s): Kanda S, Mitsuyasu T, Nakao Y, Kawano S, Goto Y, Matsubara R, Nakamura S.
  • Journal Title: Int J Oncol Volume: 43 Issue: 3 Pages: 695-802
  • DOI: 10.3892/ijo.2013.2010
  • Peer Reviewed
• [Journal Article] Fibroblast growth factors 7 and 10 are involved in ameloblastoma proliferation via the mitogen-activated protein kinase pathway. (2013)
  • Author(s): Nakao Y, Mitsuyasu T, Kawano S, Nakamura N, Kanda S, Nakamura S.
  • Journal Title: International Journal of Oncology Volume: 43 Issue: 5 Pages: 1377-1384
  • DOI: 10.3892/ijo.2013.2081
  • Peer Reviewed
• [Journal Article] Concurrence of autoantibodies to both the γ2 subunit of laminin 332 and laminin γ1 in a patient with rejection response to the transplanted kidney (2013)
  • Author(s): Eiji Mitate, Shintaro Kawano, Yu Nakao, Yuichi Goto, Ieyoshi Kobayashi, Onozawa K, Takashi Hashimoto, and Seiji Nakamura
  • Journal Title: Acta Derm Venereol Volume: 93 Pages: 114-115
  • Peer Reviewed
• [Journal Article] 臼後部に発生した多形腺腫の１例 (2012)
  • Author(s): 吉賀大午、川野真太郎、小林家吉、鈴木華子、後藤雄一、中村誠司
  • Journal Title: 日本口腔外科学会雑誌 Volume: 58 Pages: 541-545
  • NAID: 10031144937
  • Peer Reviewed
• [Journal Article] 口腔扁平苔癬および掌蹠膿疱症の発症と金属アレルギーとの関連についての検討 (2012)
  • Author(s): 森山雅文、神田詩織、川野真太郎、立石康一郎、後藤雄一、中村誠司
  • Journal Title: 日本口腔外科学会雑誌 Volume: 58 Pages: 718-722
  • NAID: 10031156063
  • Peer Reviewed
• [Journal Article] 下顎歯肉に見られた腺扁平上皮癌の１例 (2012)
  • Author(s): 見立英史、大部一成、吉賀大午、川野真太郎、河津俊幸、清島 保、豊嶋健史、北村亮二、中村誠司
  • Journal Title: 日本口腔腫瘍学会誌 Volume: 24 Pages: 55-61
  • NAID: 10031168579
  • Peer Reviewed
• [Journal Article] Clinical significance of combined assessment of the maximum standardized uptake value of F-18 FDG PET with nodal size in the diagnosis of cervical lymph node metastasis of oral squamous cell carcinoma (2012)
  • Author(s): Ryota Matsubara, Shintaro Kawano, Toru Chikui, Takahiro Kiyosue, Yuichi Goto, Mitsuhiro Hirano, Teppei Jinnno, Tetsuji Nagata, Kazunari Oobu, Koichiro Abe, and Seiji Nakamura
  • Journal Title: Academic Radiology Volume: 19 Pages: 708-717
  • Peer Reviewed
• [Journal Article] Association of cytokeratin 17 expression with differentiation in oral squamous cell carcinoma (2012)
  • Author(s): Ryoji Kitamura, Takeshi Toyoshima, Hideaki Tanaka, Shintaro Kawano, Kazunari Oobu, Takahiro Kiyosue, Ryota Matsubara, Yuichi Goto, and Seiji Nakamura
  • Journal Title: ,Journal of Cancer Research and Clinical Oncology Volume: 138 Pages: 1299-1310
  • Peer Reviewed
• [Journal Article] Association of cytokeratin 17 expression with differentiation in oral squamous cell carcinoma (2012)
  • Author(s): Kitamura R, Toyoshima T, Tanaka H, Kawano S, Kiyosue T, Matsubara R, Goto Y, Hirano M, Oobu K, Nakamura S.
  • Journal Title: J Cancer Res Clin Oncol. Volume: in press
  • Peer Reviewed
• [Journal Article] Immunohistochemical location of the p75 neurotrophin receptor (p75NTR) in oral leukoplakia and oral squamous cell carcinoma (2012)
  • Author(s): Kiyosue T, Kawano S, Matsubara R, Goto Y, Hirano M, Jinno T, Toyoshima T, Kitamura R, Oobu K, Nakamura S
  • Journal Title: Int J Clin Oncol Volume: in press
  • NAID: 10031176249
  • Peer Reviewed
• [Journal Article] IncreasedΔNp63 expression is predictive of malignant transformation in oral epithelial dysplasia and poor prognosis in oral squamous cell carcinoma (2011)
  • Author(s): R. Matsubara, S. Kawano, T. Kiyosue, Y. Goto, M. Hirano, T. Toyoshima, R. Kitamura, K. Oobu, and S. Nakamura
  • Journal Title: International Journal of Oncology Volume: 39 Pages: 1391-1399
• [Presentation] 口腔扁平上皮癌におけるIL-6の発現と臨床病理学的所見との関連 (2013)
  • Author(s): 神野哲平, 川野真太郎, 松原良太, 清末崇裕, 後藤雄一, 平野充広, 田中秀明, 丸瀬靖之, 森山雅文, 豊嶋健史, 中村誠司
  • Organizer: 第37回日本頭頸部癌学会
  • Year and Date: 2013-06-13
• [Presentation] 口腔扁平上皮癌高転移株より分離した上皮-間葉転換細胞の特性 (2013)
  • Author(s): 平野充広, 川野真太郎, 松原良太, 清末崇裕, 後藤雄一, 神野哲平, 丸瀬靖之, 豊嶋健史, 北村亮二, 田中秀明, 大部一成, 中村誠司
  • Organizer: 第17回九州地区口腔癌研究会学術講演会
  • Year and Date: 2013-06-07
• [Presentation] 口腔扁平上皮癌におけるinterleukin-6発現と臨床病理学的所見との関連 (2013)
  • Author(s): 神野哲平, 川野真太郎, 平野充広, 松原良太, 清末崇裕, 後藤雄一, 丸瀬靖之, 今藤彰子, 豊嶋健史, 田中秀明, 大部一成, 中村誠司
  • Organizer: 第31回日本口腔腫瘍学会総会
  • Year and Date: 2013-01-24
• [Presentation] 口腔扁平上皮癌由来細胞株における腫瘍関連抗原RCAS1の発現や分泌、機能についての検討 (2013)
  • Author(s): 田中 秀明, 豊嶋 健史, 園田 顕三, 北村 亮二, 川野 真太郎, 平野 充広, 神野 哲平, 丸瀬 靖之, 笹栗 正明, 大部 一成, 中村 誠司
  • Organizer: 第37回 頭頸部癌学会学術集会
  • Place of Presentation: 東京
• [Presentation] 口腔扁平上皮癌におけるIL-6の発現と臨床病理学的所見との関連 (2013)
  • Author(s): 神野 哲平, 川野 真太郎, 松原 良太, 清末 崇裕, 後藤 雄一, 平野 充広, 田中 秀明, 丸瀬 靖之, 森山 雅文, 豊嶋 健史, 大部 一成, 中村 誠司
  • Organizer: 第37回 頭頸部癌学会学術集会
  • Place of Presentation: 東京
• [Presentation] 口腔扁平上皮癌患者における術前血清CRP値の臨床的意義 (2012)
  • Author(s): 平野充広、川野真太郎、後藤雄一、松原良太、清末崇裕、北村亮二、神田詩織、村津大地、田中秀明、神野哲平、大部一成、中村誠司
  • Organizer: 第57回日本口腔外科学会総会
  • Place of Presentation: 横浜
• [Presentation] 口腔扁平上皮癌の浸潤・転移におけるΔNp63を介した上皮-間葉転換の関与 (2011)
  • Author(s): 後藤雄一, 川野真太郎, 松原良太, 清末崇裕, 平野充広, 神野哲平, 豊嶋健史, 北村亮二, 大部一成, 中村誠司
  • Organizer: 第56回日本口腔外科学会総会
  • Year and Date: 2011-10-24
• [Presentation] 口腔扁平上皮癌における浸潤・転移の分子機構の解明-ΔNp63の発現と上皮-間葉転換との関連について- (2011)
  • Author(s): 後藤雄一, 川野真太郎, 松原良太, 清末崇裕, 平野充広, 豊嶋健史, 北村亮二, 大部一成, 中村誠司
  • Organizer: 第65回日本口腔科学会学術集会
  • Year and Date: 2011-04-21
• [Remarks]
  • URL: http://www.omfs1.dent.kyushu-u.ac.jp
• [Remarks] 九州大学病院 顎口腔外科
  • URL: http://www.omfs1.dent.kyushu-u.ac.jp