Epithelial mesenchymal transition induced invasion and metastasis in oral squamous cell carcinoma via delta-Np63.

• Project/Area Number: 25870492
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Surgical dentistry; Pathobiological dentistry/Dental radiology
• Research Institution: Kagoshima University (2015); Kyushu University (2013-2014)
• Principal Investigator: Goto Yuichi 鹿児島大学, 医歯学域医学部・歯学部附属病院, 助教 (00637902)
• Research Collaborator: Kawano Shintaro 九州大学病院, 講師 (26463014) ; Matsubara Ryota 九州大学病院, 助教 (60615798) ; Sugiura Tsuyoshi 鹿児島大学, 医歯学域歯学系, 教授 (40322292) ; Nakamura Seiji 九州大学, 大学院歯学研究院, 教授 (60189040)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: ΔNp63 / EMT / 口腔扁平上皮癌 / 浸潤 / 転移 / microRNA / 浸潤転移 / 上皮間葉転換 / 病理組織学的検討 / OSCC

Outline of Final Research Achievements

Epithelial-to-mesenchymal transition (EMT), an essential developmental program, is through to be involved in tumor progression. ΔNp63, a homologue of p53, is described the association
with the EMT program, but the detail remains to be elucidate. In this study, we examined the roles of ΔNp63 in the EMT during progression of oral squamous cell carcinoma (OSCC).
Downregulation of ΔNp63 induced a mesenchymal cell-like phenotype and is possibly involved in invasion and metastasis in OSCC. Although further studies are needed to understand the complex roles of ΔNp63, revealing the functions of ΔNp63 in EMT during tumor progression will lead to new approaches for the treatment of OSCC.

Research Products

• [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 marginal zone B cell lymphoma mimicking IgG4-related dacryoadenitis and sialoadenitis. (2015)
  • Author(s): Ohta M, Moriyama M, Goto Y, Kawano S, Tanaka A, Maehara T, Furukawa S, J Hayashida JN, Kiyoshima T, Shimizu M, Arinobu Y, Nakamura S.
  • Journal Title: World J Surg Oncol Volume: 13 Issue: 1 Pages: 67-67
  • DOI: 10.1186/s12957-015-0459-z
  • Peer Reviewed / Open Access
• [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
• [Journal Article] The diagnostic utility of biopsies from the submandibular and labial salivary glands in IgG4-related dacryoadenitis and sialoadenitis, so-called Mikulicz’s disease (2014)
  • Author(s): Moriyama M, Furukawa S, Kawano S, Goto Y, Kiyoshima T, Tanaka A, Maehara T, Hayashida JN, Ohta M, Nakamura S
  • Journal Title: Int J Oral Maxillofac Surg Volume: 43 Issue: 10 Pages: 1276-1281
  • DOI: 10.1016/j.ijom.2014.06.014
  • Peer Reviewed / Open Access
• [Journal Article] Apoptotic function of tumor-associated antigen RCAS1 in oral squamous cell carcinoma (2014)
  • Author(s): Hideaki Tanaka, Takeshi Toyoshima, Kenzo Sonoda, Ryoji Kitamura, Masaaki Sasaguri, Shintaro Kawano, Ryota Matsubara, Yuichi Goto, Seiji Nakamura
  • Journal Title: Journal of Translational Medicine Volume: 12 Issue: 1 Pages: 112-112
  • DOI: 10.1186/1479-5876-12-112
  • Peer Reviewed / Open Access
• [Journal Article] Clinical relevance of Kuttner tumour and IgG4-related dacryoadenitis and sialoadenitis. (2014)
  • Author(s): Furukawa S1, Moriyama M, Kawano S, Tanaka A, Maehara T, Hayashida JN, Goto Y, Kiyoshima T, Shiratsuchi H, Ohyama Y, Ohta M, Imabayashi Y, Nakamura S.
  • Journal Title: Oral Dis Volume: 21(2) Issue: 2 Pages: 257-62
  • DOI: 10.1111/odi.12259
  • Peer Reviewed / Open Access
• [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
• [Presentation] Expression and function of kallikrein-related peptidase 6 in oral squamous cell carcinoma: the association with epithelial-mesenchymal transition mediated by ΔNp63 (2016)
  • Author(s): Naoki KANEKO, Shintaro KAWANO, Ryota MATSUBARA, Teppei JINNO, Yasuyuki MARUSE, Yuichi GOTO, Taiki SAKAMOTO, Yuma HASHIGUCHI, Ryoji KITAMURA, Hideaki TANAKA, and Seiji NAKAMURA
  • Organizer: 2016 Annual Congress of ROC Association of Oral and Maxillofacial Surgeons, Taiwan
  • Place of Presentation: 台北（Taiwan）
  • Year and Date: 2016-03-05
  • Int'l Joint Research
• [Presentation] A function of microRNA-205 associated withΔNp63 in oral squamous cell carcinoma (2016)
  • Author(s): Yuma Hashiguchi, Shintaro Kawano, Yuichi Goto, Ryota Matsubara, Teppei Jinno, Yasuyuki Maruse, Naoki Kaneko, Taiki Sakamoto, Kazunari Oobu, and Seiji Nakamura
  • Organizer: 2016 Annual Congress of ROC Association of Oral and Maxillofacial Surgeons, Taiwan
  • Place of Presentation: 台北（Taiwan）
  • Year and Date: 2016-03-05
  • Int'l Joint Research
• [Presentation] Involvement of Wnt5a-Ror2 signaling in migration of oral squamous cell c arcinoma cells through ΔNp63 down-regulation (2016)
  • Author(s): Taiki Sakamoto, , Shintaro Kawano, Ryota Matsubara, Yuichi Goto, Teppei Jinno, Yasuyuki Maruse, Naoki Kaneko, Yuma Hashiguchi, Kazunari Oobu, and Seiji Nakamura
  • Organizer: 2016 Annual Congress of ROC Association of Oral and Maxillofacial Surgeons, Taiwan
  • Place of Presentation: 台北（Taiwan）
  • Year and Date: 2016-03-05
  • Int'l Joint Research
• [Presentation] 口腔扁平上皮癌におけるΔNp63を介した浸潤・転移の分子生物学的メカニズムの 解明 ～Wnt5a-Ror2シグナル経路との関連～ (2016)
  • Author(s): Taiki Sakamoto, , Shintaro Kawano, Ryota Matsubara, Yuichi Goto, Teppei Jinno, Yasuyuki Maruse, Naoki Kaneko, Yuma Hashiguchi, Kazunari Oobu, and Seiji Nakamura
  • Organizer: 第34回日本口腔腫瘍学会総会・学術大会
  • Place of Presentation: 横浜市開港記念会館（神奈川県横浜市）
  • Year and Date: 2016-01-21
• [Presentation] Downregulation of delta-Np63 induces a mesenchymal cell phenotype, possibly involving invasion and metastasis of OSCC (2015)
  • Author(s): Yuichi Goto, Shintaro Kawano, Koudai Nakamura, Tomofumi Hamada, Seiji Nakamura, Tsuyoshi Sugiura
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場（愛知県名古屋市）
  • Year and Date: 2015-10-09
• [Presentation] Clinicopathological evaluation of preoperative chemoradiotherapy with S-1 for locally advanced OSCC (2015)
  • Author(s): Yuma hashiguchi , Shintaro Kawano , Kazunari Oobu , Ryota Matsubara , Yuichi Goto , Teppei Jinno , Yasuyuki Maruse , Taiki Sakamoto , Naoki Kaneko , Masahiko Morioka , and Seiji Nakamura
  • Organizer: 第34回日本口腔腫瘍学会総会・学術大会
  • Place of Presentation: 神戸国際会議場（兵庫県神戸市）
  • Year and Date: 2015-06-03
• [Presentation] Usefulness of postoperative chemoradiotherapy for cervical lymph nodes metastasis of OSCC (2015)
  • Author(s): Naoki Kaneko, Kazunari Oobu, Ryota Matsubara, Yuichi Goto, Shintaro Kawano, Teppei Jinno, Yasuyuki Maruse，Taiki Sakamoto, Yuma Hashiguchi, Masahiko Morioka, Seiji Nakamura
  • Organizer: 第39回日本頭頚部癌学会・第4回アジア頭頸部癌学会
  • Place of Presentation: 神戸国際会議場（兵庫県神戸市）
  • Year and Date: 2015-06-03
  • Int'l Joint Research
• [Presentation] A clinicopathological study of malignant salivary gland tumors (2015)
  • Author(s): Taiki Sakamoto, , Shintaro Kawano, Ryota Matsubara, Yuichi Goto, Teppei Jinno, Yasuyuki Maruse, Naoki Kaneko, Yuma Hashiguchi, Kazunari Oobu, and Seiji Nakamura
  • Organizer: 第39回日本頭頚部癌学会・第4回アジア頭頸部癌学会
  • Place of Presentation: 神戸国際会議場（兵庫県神戸市）
  • Year and Date: 2015-06-03
  • Int'l Joint Research
• [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 (2015)
  • Author(s): 後藤雄一、川野真太郎、松原良太、神野哲平、丸瀬靖之、橋口有真、金子直樹、坂本泰基、田中秀明、北村亮二、大部一成、杉浦剛、中村誠司
  • Organizer: 第69回NPO法人日本口腔科学会学術集会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2015-04-13 – 2015-04-15
• [Presentation] 口腔扁平上皮癌における IL-6 の発現と機能～抗癌剤抵抗性獲得への関与について～ (2014)
  • Author(s): 神野哲平、川野真太郎、松原良太、後藤雄一、清島 保、丸瀬靖之、神野彰子、 金子直樹，坂本泰基，橋口有真，森山雅文，大部一成、杉浦剛、中村誠司
  • Organizer: 第68回日本口腔科学会学術集会
  • Place of Presentation: 京王プラザホテル
  • Year and Date: 2014-05-07 – 2014-05-09
• [Presentation] 唾液腺悪性腫瘍の臨床病理学的検討 (2014)
  • Author(s): 坂本泰基，後藤雄一，川野真太郎，今藤彰子，松原良太，神野哲平，丸瀬靖之，金子直樹，橋口有真，大部一成，杉浦 剛，中村誠司
  • Organizer: 第32回日本口腔腫瘍学会総会・学術大会
  • Place of Presentation: 北海道札幌市
• [Presentation] 口腔扁平上皮癌頸部転移に対する術後治療の有用性についての検討 (2014)
  • Author(s): 金子直樹，大部一成，後藤雄一，川野真太郎，橋口有真，松原良太，神野哲平，丸瀬靖之，坂本泰基，三上友理恵，杉浦 剛，中村誠司
  • Organizer: 第32回日本口腔腫瘍学会総会・学術大会
  • Place of Presentation: 北海道札幌市
• [Presentation] Down-regulation of ΔNp63 possibly involves in the progression of oral squamous cell carcinoma by inducing mesenchymal phenotype (2013)
  • Author(s): Yuichi Goto, Shintaro Kawano, Ryota Matsubara, Takahiro Kiyosue, Mitsuhiro Hirano, Teppei Jinno, Yasuyuki Maruse, Takeshi Toyoshima, Ryoji Kitamura, Hideaki Tanaka, Kazunari Oobu, and Seiji Nakamura
  • Organizer: 6th International p63/p73 Workshop
  • Place of Presentation: 千葉県木更津市