Elucidation of the role of Jab1 in malignant progression of colon cancer

2013 Fiscal Year Final Research Report

• Project/Area Number: 24791425
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Digestive surgery
• Research Institution: Yamaguchi University
• Principal Investigator: NISHIMOTO Arata 山口大学, 医学(系)研究科(研究院), 助教 (90396325)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Keywords: ヒト大腸癌細胞 / JAB1 / STAT3 / 蛋白質間相互作用 / STAT3標的DNA結合能

Research Abstract

Immunoprecipitation using nuclear extract of human colon cancer cells revealed that JAB1 interacted with STAT3. To investigate the effect of JAB1 on STAT3 activity, RNAi studies were performed. JAB1 knockdown decreased STAT3 DNA-binding activity and the expression levels of MDR1, NANOG, and VEGF, which are STAT3 target genes. Furthermore, JAB1 knockdown increased anti-cancer drug-induced apoptosis. Taken together, these results suggest that JAB1 contributes to the acquisition of drug resistance by stabilizing STAT3 DNA-binding through protein-protein interaction in human colon cancer cells.

Research Products

• [Journal Article] HIF-1α activation under glucose deprivation plays a central role in the acquisition of anti-apoptosis in human colon cancer cells (2014)
  • Author(s): Nishimoto A, Kugimiya N, Hosoyama T, Enoki T, Li TS, Hamano K
  • Journal Title: Int J Oncol Volume: 44(6) Pages: 2077-84
  • Peer Reviewed
• [Journal Article] Hypoxic preconditioning reinforces cellular functions of autologous peripheral blood-derived cells in rabbit hindlimb ischemia model (2014)
  • Author(s): Kudo T, Hosoyama T, Samura M, Katsura S, Nishimoto A, Kugimiya N, Fujii Y, Li TS, Hamano K
  • Journal Title: Biochem Biophys Res Commun Volume: 444(3) Pages: 370-5
  • Peer Reviewed
• [Journal Article] JAB1 regulates unphosphorylated STAT3 DNA-binding activity through protein-protein interaction in human colon cancer cells (2013)
  • Author(s): Nishimoto A, Kugimiya N, Hosoyama T, Enoki T, Li TS, Hamano K
  • Journal Title: Biochem Biophys Res Commun Volume: 438(3) Pages: 513-8
  • Peer Reviewed
• [Journal Article] Significant role of bone marrow-derived cells in compensatory regenerative lung growth (2013)
  • Author(s): Suga A, Ueda K, Takemoto Y, Nishimoto A, Hosoyama T, Li TS, Hamano K
  • Journal Title: J Surg Res Volume: 183(1) Pages: 84-90
  • Peer Reviewed
• [Journal Article] Heat shock factor 1 contributes to ischemia-induced angiogenesis by regulating the mobilization and recruitment of bone marrow stem/progenitor cells (2012)
  • Author(s): Kubo M, Li TS, Kurazumi H, Takemoto Y, Ohshima M, Yamamoto Y, Nishimoto A, Mikamo A, Fujimoto M, Nakai A, Hamano K
  • Journal Title: PLoS One Volume: 7(5) Pages: e37934
  • Peer Reviewed
• [Presentation] Jab1 plays an important role in drug resistance by stabilizing STAT3 and HIF-1 DNA-binding (2013)
  • Author(s): Arata Nishimoto, Naruji Kugimiya, Tohru Hosoyama, Tadahiko Enoki, Tao-Sheng Li, Kimikazu Hamano
  • Organizer: 9th AACR-Japanese Cancer Association Joint Conference
  • Place of Presentation: Maui (Hawaii, USA)
  • Year and Date: 20130221-25
• [Presentation] JAB1 は蛋白質間相互作用を介してSTAT3 及びHIF-1α の標的DNAへの結合を安定化し抗アポトーシス活性を増強させる (2013)
  • Author(s): 西本 新, 釘宮成二, 村上順一, 上田和弘, 濱野公一
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: 横浜(パシフィコ横浜)
  • Year and Date: 2013-10-05
• [Presentation] Jab1 はSTAT3 の標的DNA 配列に対する結合能を蛋白質間相互作用を介して正に制御する (2012)
  • Author(s): 西本 新, 村上順一, 上田和弘
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌(ロイトン札幌)
  • Year and Date: 20120919-25