Roles of the tumor suppressor CYLD in progression and personalized medicine of oral cancer

• Project/Area Number: 24792238
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Surgical dentistry
• Research Institution: Kumamoto University
• Principal Investigator: SHINRIKI Satoru 熊本大学, 医学部附属病院, 特任助教 (00583048)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 国際情報交換 / 口腔扁平上皮癌 / CYLD / TGFβ / EMT / アメリカ

Research Abstract

We obtained the results as follows;1. Expression of Cylindromatosis (CYLD) was reduced in invasive region in oral squamous cell carcinoma (OSCC) tissues, which was significantly associated with increased Smad3 phosphorylation and worse prognosis. 2. CYLD knockdown inhibited SMURF2-dependent degradation of TGFBR1, leading to promoted TGFbeta signaling activation, acquisition of mesenchymal state and increased migration. 3. CYLD repression led to resistance to cisplatin but increased susceptibility to EGFR tyrosine kinase inhibitor-inducible apoptosis in OSCC cells. 4. Loss of CYLD induced long-term quiescent state in OSCC cells in vitro.

Research Products

• [Presentation] CYLD の発現低下は ALK5 の安定化を介して口腔扁平上皮癌の遊走を促進させる (2013)
  • Author(s): 神力悟, 城野博史, 中村拓哉, 郭建エイ, 林光博, 田崎雅義, 大林光念, 篠原正徳, 安東由喜雄
  • Organizer: 第72回日本癌学会学術集会
  • Place of Presentation: 横浜
• [Presentation] Loss of CYLD promotes cell migration through stabilized ALK5 in human oral squamous cell carcinoma cells (2013)
  • Author(s): Shinriki S, Jono H, Li JD, Nakamura T, Hayashi M, Guo J, Shinohara M, Ando Y
  • Organizer: 104th AACR Annual Meeting 2013
  • Place of Presentation: Washington DC, USA
• [Presentation] Loss of CYLD promotes cell migration through stabilized ALK5 in human oral squamous cell carcinoma cells. (2013)
  • Author(s): 神力悟
  • Organizer: 104th AACR Annual Meeting 2013
  • Place of Presentation: Washington Convention Center (Washington DC, USA)
• [Presentation] CYLDの発現低下はALK5の安定化を介して口腔扁平上皮癌の遊走を促進させる. (2013)
  • Author(s): 神力悟
  • Organizer: 第72回日本癌学会学術集会
  • Place of Presentation: パシフィコ横浜（横浜）
• [Presentation] CYLD の発現低下は口腔扁平上皮癌の進展を促進すると同時に EGFR標的治療の感受性を増加させる (2012)
  • Author(s): 神力悟, 中村拓哉, 林光博, 篠原正徳, 安東由喜雄
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
• [Presentation] 頭頸部扁平上皮癌におけるCYLD の発現低下は EGFR を介して高度悪性形質の獲得を誘導する (2012)
  • Author(s): 神力悟, 城野博史, 大林光念, 田崎雅義, 安東由喜雄
  • Organizer: 第52回日本臨床化学会年次学術集会
  • Place of Presentation: 盛岡
• [Presentation] Downregulation of CYLD leads to acquisition of mesenchymal state and increased migration via ligand-independent TGFβR1 activation in human oral squamous cell carcinoma cells (2012)
  • Author(s): Shinriki S, Jono H, Nakamura T, Hayashi M, Yamamoto Y, Ibusuki M, Sueyoshi T, Ota T, Shinohara M, Ando Y
  • Organizer: 103rd AACR Annual Meeting 2012
  • Place of Presentation: Chicago, Illinois, USA
• [Presentation] Downregulation of CYLD leads to acquisition of mesenchymal state and increased migration via ligand-independent TGFβR1 activation in human oral squamous cell carcinoma cells. (2012)
  • Author(s): 神力 悟
  • Organizer: 103th AACR Annual Meeting 2012
  • Place of Presentation: McCormick Place (Chicago, USA)
• [Presentation] CYLDの発現低下は口腔扁平上皮癌の進展を促進すると同時にEGFR標的治療の感受性を増加させる。 (2012)
  • Author(s): 神力 悟
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌芸文館（札幌市）
• [Presentation] 頭頸部扁平上皮癌におけるCYLDの発現低下はEGFRを介して高度悪性形質の獲得を誘導する。 (2012)
  • Author(s): 神力 悟
  • Organizer: 第52回日本臨床化学会年次学術集会
  • Place of Presentation: いわて県民情報交流センター（盛岡市）