Quiescent tumor cell models for regulating tumor dormancy

• Project/Area Number: 26861735
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Surgical dentistry
• Research Institution: Kumamoto University (2015); Hamamatsu University School of Medicine (2014)
• Principal Investigator: Shinriki Satoru 熊本大学, 大学院生命科学研究部, 講師 (00583048)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 静止期癌細胞 / 骨髄播種癌細胞 / CYLD / 抗癌剤耐性

Outline of Final Research Achievements

Suppression of CYLD expression by siRNA in head and neck squamous cell carcinoma (HNSCC) cell lines led to an increase in G0 phase. Although, to establish a quiescent tumor cell model, we utilized Tet-on shRNA to regulate CYLD expression, the knockdown efficacy has been insufficient. Therefore, further investigation is needed.
Besides, we established a dormant bone marrow-disseminated tumor cell (BM-DTC)-derived subclone using OSCC cell line, HEp3. Using this subclone, we reported that intrinsic TGF-β2-SDF-1-CXCR4 signaling was important for slow-cycling state and drug resistance in dormant BM-DTC.

Research Products

• [Journal Article] Intrinsic TGF-β2-triggered SDF-1-CXCR4 signaling axis is crucial for drug resistance and a slow-cycling state in bone marrow-disseminated tumor cells. (2015)
  • Author(s): Nakamura T, Shinriki S, Jono H, Guo J, Ueda M, Hayashi M, Yamashita S, Zijlstra A, Nakayama H, Hiraki A, Shinohara M, Ando Y.
  • Journal Title: Oncotarget Volume: 6 Pages: 1008-1019
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Osteopontin-integrin α(v)β(3) axis is crucial for 5-fluorouracil resistance in oral squamous cell carcinoma. (2015)
  • Author(s): Nakamura T, Shinriki S, Jono H, Ueda M, Nagata M, Guo J, Hayashi M, Yoshida R, Ota T, Ota K, Kawahara K, Nakagawa Y, Yamashita S, Nakayama H, Hiraki A, Shinohara M, Ando Y.
  • Journal Title: FEBS Lett Volume: 589 Issue: 2 Pages: 231-239
  • DOI: 10.1016/j.febslet.2014.12.004
  • Peer Reviewed / Open Access
• [Journal Article] Hypoxia suppresses cylindromatosis (CYLD) expression to promote inflammation in glioblastoma: possible link to acquired resistance to anti-VEGF therapy. (2014)
  • Author(s): Guo J, Shinriki S, Su Y, Nakamura T, Hayashi M, Tsuda Y, Murakami Y, Tasaki M, Hide T, Takezaki T, Kuratsu J, Yamashita S, Ueda M, Li JD, Ando Y, Jono H.
  • Journal Title: Oncotarget Volume: 5 Pages: 6353-6364
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] 骨髄播種癌細胞の増殖抑制状態と抗癌剤耐性への細胞自律的制御機構の関与 (2015)
  • Author(s): 神力 悟
  • Organizer: 第62回日本臨床検査医学会学術集会
  • Place of Presentation: 長良川国際会議場、岐阜
  • Year and Date: 2015-11-19
• [Presentation] 骨髄播種癌細胞が自律的に誘導する増殖抑制状態と抗癌剤耐性 (2015)
  • Author(s): 神力 悟
  • Organizer: 第55回日本臨床化学会年次学術集会
  • Place of Presentation: 大阪大学、大阪
  • Year and Date: 2015-10-30
• [Presentation] Intrinsic molecular characteristics of bone marrow-disseminated tumor cells (2015)
  • Author(s): 神力 悟
  • Organizer: 第74回日本癌学会学術集会
  • Place of Presentation: 名古屋国際会議場、名古屋
  • Year and Date: 2015-10-08
• [Presentation] Loss of CYLD promotes cell migration by inhibiting Smurf2-dependent ALK5 degradation in oral squamous cell carcinoma. (2014)
  • Author(s): 神力悟
  • Organizer: 第19回静岡健康・長寿学術フォーラム
  • Place of Presentation: プラサ ヴェルテ（ふじのくに千本松フォーラム）, 沼津
  • Year and Date: 2014-11-07 – 2014-11-08
• [Presentation] CYLDの発現低下はSmurf2依存的なALK5の分解を阻害することで口腔扁平上皮癌の遊走を促進させる (2014)
  • Author(s): 神力悟
  • Organizer: 第73回日本癌学会学術集会
  • Place of Presentation: パシフィコ横浜, 横浜
  • Year and Date: 2014-09-25 – 2014-09-27