AP-1 family as a key molecule in the regulation of the pathways related to regional metastasis in head and neck squamous cell carcinoma

• Project/Area Number: 26861406
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Otorhinolaryngology
• Research Institution: Yokohama City University
• Principal Investigator: SANO Daisuke 横浜市立大学, 医学部, 助教 (10620990)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2015: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000); Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: 頭頸部癌 / 遠隔転移 / AP-1 / 転移 / AP-1 遺伝子群

Outline of Final Research Achievements

We initially performed the upstream and key nodes analysis related with whole gene microarray analysis characterized by distant metastatic potential in vivo with HNSCC cell lines and identified JunB, member of the activated protein-1 (AP-1) family, as a key molecule regulating the pathways related with distant metastasis of HNSCC. Small interfering RNA (siRNA)-mediated knockdown of JunB, and Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (cas9) system (CRISPR/Cas9)-mediated knockout of JunB in HNSCC cells, markedly suppressed the ability of invasion and migration in vitro. In addition, knockout of JunB significantly repressed the incidence of lung metastases in vivo. These results suggested that JunB could play an important role to promote cell invasion, migration and distant metastasis of HNSCC.

Research Products

• [Journal Article] JunB promotes cell invasion, migration and distant metastasis of head and neck squamous cell carcinoma (2016)
  • Author(s): Hyakusoku H, Sano D, Takahashi H, Hatano T, Isono Y, Shimada S, Ito Y, Myers JN, Oridate N
  • Journal Title: J Exp Clin Cancer Res Volume: 35 Issue: 1 Pages: 6-6
  • DOI: 10.1186/s13046-016-0284-4
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] volutionary Action Score of TP53 Identifies High-Risk Mutations Associated with Decreased Survival and Increased Distant Metastases in Head and Neck Cancer (2015)
  • Author(s): Neskey DM, Osman AA, Ow TJ, Katsonis P, McDonald T, Hicks SC, Hsu TK, Pickering CR, Ward A, Patel A, Yordy JS, Skinner HD, Giri U, Sano D, Story MD, Beadle BM, El-Naggar AK, Kies MS, William WN, Caulin C, Frederick M, Kimmel M, Myers JN, Lichtarge O
  • Journal Title: Cancer Res Volume: 75 Issue: 7 Pages: 1527-1536
  • DOI: 10.1158/0008-5472.can-14-2735
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] よくわかる遺伝子 機能と遺伝子 頭頸部癌と遺伝子 (2014)
  • Author(s): 佐野大佑、折舘伸彦
  • Journal Title: JOHNS Volume: 30 Pages: 719-722
• [Presentation] JunB promotes distant metastasis of head and neck squamous cell carcinoma (2015)
  • Author(s): Sano D, Hyakusoku H, Takahashi H, Hatano T, Isono Y, Oridate N
  • Organizer: 74th Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: 名古屋国際会議場（愛知県）
  • Year and Date: 2015-10-08
  • Int'l Joint Research
• [Presentation] 頭頸部癌遠隔転移進展におけるAP-1遺伝子群の関与についての検討 (2015)
  • Author(s): 百束紘，佐野大佑，高橋秀聡、波多野孝，磯野泰大，荒井康裕，折舘伸彦
  • Organizer: 第116回日本耳鼻咽喉科学会総会
  • Place of Presentation: 東京国際フォーラム（東京都）
  • Year and Date: 2015-05-20
• [Presentation] AP-1 family promotes cell invasion and metastasis in head and neck squamous cell carcinoma in vivo. (2014)
  • Author(s): 1.Sano D, Hyakusoku H, Takahashi H, Hatano T, Isono Y, Oridate N
  • Organizer: 73rd Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] The comprehensive profile with the upstream and key nodes analysis for regional and distant metastatic potential of head and neck squamous cell carcinoma in vivo (2014)
  • Author(s): Sano D, Hyakusoku H, Takahashi H
  • Organizer: 5th World Congress of IFHNOS
  • Place of Presentation: ニューヨーク（アメリカ合衆国）
  • Year and Date: 2014-07-26 – 2014-07-30
• [Presentation] 遺伝子カスケード解析による頭頸部癌マウスモデルにおける頸部リンパ節・遠隔転移能に対する検討 (2014)
  • Author(s): 佐野大佑、高橋秀聡、折舘伸彦
  • Organizer: 第38回日本頭頸部癌学会
  • Place of Presentation: 東京ファッションタウンビルホール（東京都江東区）
  • Year and Date: 2014-06-12 – 2014-06-13
• [Presentation] 遺伝子カスケード解析による同所性頭頸部癌モデルにおける頸部リンパ節転移能に対する検討 (2014)
  • Author(s): 佐野大佑、百束紘、高橋秀聡、荒井康裕、高橋優宏、西村剛志、折舘伸彦
  • Organizer: 第115回日本耳鼻咽喉科学会総会・学術講演会
  • Place of Presentation: ヒルトン福岡シーホーク（福岡県福岡市）
  • Year and Date: 2014-05-14 – 2014-05-17