Active glucose metabolism and tumor promotion mediated by Pkm1

• Project/Area Number: 16K14621
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Tumor biology
• Research Institution: Miyagi Prefectural Hospital Organization Miyagi Cancer Center
• Principal Investigator: TANUMA Nobuhiro 地方独立行政法人宮城県立病院機構宮城県立がんセンター(研究所), がん薬物療法研究部, 主任研究員 (40333645)
• Project Period (FY): 2016-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2016: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
• Keywords: Pkm / グルコース代謝 / オートファジー / がん細胞の特性

Outline of Final Research Achievements

In this study, we explored how Pkm1 promotes tumor growth/survival. We found that the mode of Pkm1's action is tumor cell-intrinsic. Pkm1-expressing cells combine active TCA cycle and lower ROS levels in mitochondria through mitophagy. Importantly, this metabolic rewiring by Pkm1 impedes neither pentose phosphate pathway nor purine synthesis. Our results unveil tumor-promoting function of Pkm1.

Research Products

• [Journal Article] The enhanced expression of PKM2 is involved in the gastric cancer development via regulating cancer specific metabolism (2017)
  • Author(s): Shiroki T. et al.
  • Journal Title: Cancer Science Volume: 印刷中
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] The protein phosphatase 6 catalytic subunit (Ppp6c) is indispensable for proper post-implantation embryogenesis. (2016)
  • Author(s): Ogoh, H., Tanuma, N., Matsui, Y., Hayakawa, N., Inagaki, A., Sumiyoshi, M., Momoi, Y., Kishimoto, A., Suzuki, M., Sasaki, N., Ohuchi, T., Nomura, M., Teruya, Y., Yasuda, K., Watanabe, T., Shima, H.
  • Journal Title: Mechanisms of Development Volume: 139 Pages: 1-9
  • DOI: 10.1016/j.mod.2016.02.001
  • Peer Reviewed / Open Access
• [Presentation] 小細胞肺がんの代謝特性と、その標的化戦略 (2016)
  • Author(s): 野村美有樹ほか
  • Organizer: 第39回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2016-11-30
• [Presentation] 起源細胞でのPKMスイッチが、腫瘍細胞のブドウ糖代謝様式を規定する (2016)
  • Author(s): 盛田麻美ほか
  • Organizer: 第10回オートファジー研究会
  • Place of Presentation: 越後湯沢
  • Year and Date: 2016-11-13
• [Presentation] PKMノックアウトマウスは胎生致死となる (2016)
  • Author(s): 田中遼太ほか
  • Organizer: 第75回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2016-10-06
• [Presentation] 小細胞肺がんにおけるPkm1の役割 (2016)
  • Author(s): 盛田麻美ほか
  • Organizer: 第75回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2016-10-06
• [Presentation] 小細胞肺がんにおけるPyruvate kinase Mの発現と機能解析 (2016)
  • Author(s): 盛田麻美ほか
  • Organizer: 第89回日本生化学会大会
  • Place of Presentation: 仙台
  • Year and Date: 2016-09-25