The role of SIRT6 protein in gynecologic cancer.

• Project/Area Number: 26861348
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Obstetrics and gynecology
• Research Institution: Research Institute for Clinical Oncology, Saitama Cancer Center
• Principal Investigator: Miyamoto Yuichiro 埼玉県立がんセンター(臨床腫瘍研究所), その他部局等, その他 (70634955)
• Co-Investigator(Kenkyū-buntansha): SAKURABASHI Ayako 東京大学, 大学院医学系研究科 生殖・発達・加齢医学, 大学院生 ; FUKUDA Tomohiko 東京大学, 大学院医学系研究科 生殖・発達・加齢医学, 大学院生 (40433510)
• 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: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 子宮体癌 / SIRT6 / サバイビン / YM155 / 子宮体癌治療 / 抗酸化ストレス / 分子メカニズム解明

Outline of Final Research Achievements

The NAD-dependent deacetylase SIRT6 is participated in cancer metabolism and thought to be one of the molecular target in the treatment of the endometrial cancer.
The overall survival rate is preferable in SIRT6 overexpression group than underexpression group in our endometrial cancer clinical specimen. Moreover, SIRT6 protein induced cell death in endometrial cancer cell lines, via suppression the expression of survivin, which is an apoptotic related protein and the putative target of cancer therapy. We revealed the Survivin inhibitor YM155 prevent the cell growth of endometrial cancer. From these results, the inhibition of Survivin protein function via SIRT6 is supposed to be the putative target of endometrial cancer treatment.

Research Products

• [Journal Article] Putative tumor suppression function of SIRT6 in endometrial cancer. (2015)
  • Author(s): Fukuda T, Wada-Hiraike O, Oda K, Tanikawa M, Makii C, Inaba K, Miyasaka A, Miyamoto Y, Yano T, Maeda D, Sasaki T, Kawana K, Fukayama M, Osuga Y, Fujii T.
  • Journal Title: FEBS Lett Volume: 589 Issue: 17 Pages: 2274-2281
  • DOI: 10.1016/j.febslet.2015.06.043
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] HAND2-mediated proteolysis negatively regulates the function of estrogen receptor α. (2015)
  • Author(s): Fukuda T, Shirane A, Wada-Hiraike O, Oda K, Tanikawa M, Sakuabashi A, Hirano M, Fu H, Morita Y, Miyamoto Y, Inaba K, Kawana K, Osuga Y, Fujii T.
  • Journal Title: Mol Med Rep. Volume: 12(4) Pages: 5538-44
  • Peer Reviewed
• [Journal Article] CCAR2 negatively regulates nuclear receptor LXRα by competing with SIRT1 deacetylase. (2015)
  • Author(s): Sakurabashi A, Wada-Hiraike O, Hirano M, Fu H, Isono W, Fukuda T, Morita Y, Tanikawa M, Miyamoto Y, Oda K, Kawana K, Osuga Y, Fujii T.
  • Journal Title: J Steroid Biochem Mol Biol. Volume: 149 Pages: 80-8
  • Peer Reviewed
• [Presentation] HAND2 could serve as a tumor suppressor by inhibiting the transactivation function of ERα in endometrial carcinoma (2015)
  • Author(s): Tomohiko Fukuda, Osamu Wada-Hiraike, Katsutoshi Oda, Akira Shirane, Michihiro Tanikawa, Ayako Sakuabashi, Mana Hirano, Yuichiro Miyamoto, Kenbun Sone, Kanako Inaba, Kei Kawana, Yutaka Osuga, and Tomoyuki Fujii
  • Organizer: 第67回日本産科婦人科学会学術講演会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2015-04-09