To verify the role of phosphoglycerate mutase expression in pancreatic cancer through glucose metabolism and cellular senescence

• Project/Area Number: 18K16369
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Kumamoto University
• Principal Investigator: Kaida Takayoshi 熊本大学, 病院, 非常勤診療医師 (80792580)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 膵癌 / PGAM / セリン生合成 / 代謝リモデリング / 解糖系 / PHGDH / がん代謝 / 細胞老化 / 癌代謝

Outline of Final Research Achievements

Pancreatic cancer is a disease with a poor prognosis because there is still no effective anticancer drug. Phosphoglycerate mutase (PGAM) protein in the energy production pathway might be involved in pancreatic carcinogenesis.
It was also found that PGAM is related with the serine biosynthesis system and that the expression of PHGDH which produced into serine biosynthesis is induced in pancreatic cancer cells starved of serine. We suggest that the serine-starved diet might have an antitumor effect.

Academic Significance and Societal Importance of the Research Achievements

膵癌は未だ有効な抗癌剤治療がなく予後不良疾患である。エネルギー産生経路に関わるPGAM(phosphoglycerate mutase)といったタンパクが膵発癌に大きく関わっている可能性が示唆された。またPGAMはセリン生合成系にも関与しており、セリン飢餓状態の膵癌細胞においてセリン合成に関与するPHGDHの発現が誘導されていることがわかった。セリン飢餓食が抗腫瘍効果をもたらす可能性が示唆せれた。

Research Products

• [Journal Article] Multimodal radiofrequency ablation versus laparoscopic hepatic resection for the treatment of primary hepatocellular carcinoma within Milan criteria in severely cirrhotic patients: long-term favorable outcomes over 10 years. (2019)
  • Author(s): Yamashita YI, Imai K, Kaida T, Yamao T, Tsukamoto M, Nakagawa S, Okabe H, Chikamoto A, Ishiko T, Yoshizumi T, Ikeda T, Maehara Y, Baba H.
  • Journal Title: Surg Endsc. Volume: 33(1) Issue: 1 Pages: 46-51
  • DOI: 10.1007/s00464-018-6264-3
  • Peer Reviewed
• [Journal Article] Enhancer of zeste homolog 2 (EZH2) regulates tumor angiogenesis and predicts recurrence and prognosis of intrahepatic cholangiocarcinoma (2018)
  • Author(s): Nakagawa Shigeki、Okabe Hirohisa、Ouchi Mayuko、Tokunaga Ryuma、Umezaki Naoki、Higashi Takaaki、Kaida Takatoshi、Arima Kota、Kitano Yuki、Kuroki Hideyuki、Mima Kosuke、Nitta Hidetoshi、Imai Katsunori、Hashimoto Daisuke、Yamashita Yo-ichi、Chikamoto Akira、Baba Hideo
  • Journal Title: HPB Volume: 20 Issue: 10 Pages: 939-948
  • DOI: 10.1016/j.hpb.2018.03.018
  • Peer Reviewed
• [Journal Article] Tumor-infiltrating inflammatory and immune cells in patients with extrahepatic cholangiocarcinoma. (2018)
  • Author(s): Kitano Y, Okabe H, Yamashita YI, Nakagawa S, Saito Y, Umezaki N, Tsukamoto M, Yamao T, Yamamura K, Arima K, Kaida T, Miyata T, Mima K, Imai K, Hashimoto D, Komohara Y, Chikamoto A, Ishiko T, Baba H
  • Journal Title: Br J Cancer Volume: 118(2) Issue: 2 Pages: 171-180
  • DOI: 10.1038/bjc.2017.401
  • Peer Reviewed / Open Access
• [Presentation] 膵癌進展におけるPHGDH発現とセリン生合成の意義 (2019)
  • Author(s): 伊東山瑠美、石本崇胤、Luke Bu、米村敦子、三宅慧輔、内原智幸、有馬浩太、山下洋市、近本亮、馬場秀夫
  • Organizer: 第74回 日本消化器外科学会総会
• [Presentation] 膵癌特異的なセリン飢餓への応答メカニズムの解明 (2019)
  • Author(s): 伊東山瑠美、石本崇胤、Luke Bu、米村敦子、三宅慧輔、北村文優、内原智幸、山下洋市、近本亮、馬場秀夫
  • Organizer: 第7回 がんと代謝研究会
• [Presentation] Significance of PHGDH expression and serine biosynthesis in pancreatic cancer progression (2019)
  • Author(s): Rumi Itoyama, Takatsugu Ishimoto, Fumimasa Kitamura, Takahiko Akiyama, Luke Bu, Atsuko Yonemura, Keisuke Miyake, Tomoyuki Uchihara, Yo-ichi Yamashita, Hideo Baba
  • Organizer: 第78回 日本癌学会学術総会