Elucidation of the role of glutamine as a metabolic signaling molecule in cancer stem cells.

• Project/Area Number: 16K18410
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Tumor biology
• Research Institution: Yamagata University
• Principal Investigator: KURAMOTO Kenta 山形大学, 医学部, 助教 (80768755)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: がん幹細胞 / グルタミン代謝

Outline of Final Research Achievements

Cancer stem cells, which possess both self-renewal capacity and tumor initiation capacity, are thought to be involved in secondary tumor development and cancer recurrence. The roles of glutamine and its metabolites in the stemness of cancer stem cells are poorly understood. In this study, I demonstrate that glutamine depletion leads to a decrease in both expression levels of cancer stem cell markers and sphere forming capacity in pancreatic cancer stem cells. These results indicate that glutamine metabolism in cancer stem cells could be a target for cancer stem cells therapy.

Research Products

• [Journal Article] Licochalcone A specifically induces cell death in glioma stem cells via mitochondrial dysfunction. (2017)
  • Author(s): Kuramoto K, Suzuki S, Sakaki H, Takeda H, Sanomachi T, Seino S, Narita Y, Kayama T, Kitanaka C, Okada M.
  • Journal Title: FEBS Open Bio. Volume: 7 Issue: 6 Pages: 835-844
  • DOI: 10.1002/2211-5463.12226
  • Peer Reviewed / Open Access
• [Journal Article] Antitumor activity of gemcitabine against high-grade meningioma in vitro and in vivo. (2017)
  • Author(s): Takeda H, Okada M, Kuramoto K, Suzuki S, Sakaki H, Sanomachi T, Seino S, Yoshioka T, Hirano H, Arita K, Kitanaka C.
  • Journal Title: Oncotarget. Volume: 8 Issue: 53 Pages: 90996-91008
  • DOI: 10.18632/oncotarget.18827
  • Peer Reviewed / Open Access
• [Journal Article] Olanzapine, an Atypical Antipsychotic, Inhibits Survivin Expression and Sensitizes Cancer Cells to Chemotherapeutic Agents. (2017)
  • Author(s): Sanomachi Tomomi、Suzuki Shuhei、Kuramoto Kenta、Takeda Hiroyuki、Sakaki Hirotsugu、Togashi Keita、Seino Shizuka、Yoshioka Takashi、Okada Masashi、Kitanaka Chifumi
  • Journal Title: Anticancer Res. Volume: 37 Pages: 6177-6188
  • Peer Reviewed
• [Journal Article] Repositioning CEP-1347, a chemical agent originally developed for the treatment of Parkinson's disease, as an anti-cancer stem cell drug. (2017)
  • Author(s): Okada M, Takeda H, Sakaki H, Kuramoto K, Suzuki S, Sanomachi T, Togashi K, Seino S, Kitanaka C.
  • Journal Title: Oncotarget. Volume: 8 Issue: 55 Pages: 94872-94882
  • DOI: 10.18632/oncotarget.22033
  • Peer Reviewed / Open Access
• [Journal Article] Rho-Associated Protein Kinase (ROCK) Inhibitors Inhibit Survivin Expression and Sensitize Pancreatic Cancer Stem Cells to Gemcitabine. (2016)
  • Author(s): Takeda H, Okada M, Suzuki S, Kuramoto K, Sakaki H, Watarai H, Sanomachi T, Seino S, Yoshioka T, Kitanaka C.
  • Journal Title: Anticancer Res. Volume: 12 Issue: 12 Pages: 6311-6318
  • DOI: 10.21873/anticanres.11227
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Aripiprazole, an Antipsychotic and Partial Dopamine Agonist, Inhibits Cancer Stem Cells and Reverses Chemoresistance. (2016)
  • Author(s): Suzuki S, Okada M, Kuramoto K, Takeda H, Sakaki H, Watarai H, Sanomachi T, Seino S, Yoshioka T, Kitanaka C.
  • Journal Title: Anticancer Res. Volume: 10 Issue: 10 Pages: 5153-5161
  • DOI: 10.21873/anticanres.11085
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Autophagy activation by novel inducers prevents BECN2-mediated drug tolerance to cannabinoids. (2016)
  • Author(s): K. Kuramoto, N. Wang, Y. Fan, W. Zhang, FJ. Schonen, KJ. Frankowski, J. Marugan, Y. Zhou, S. Huang, C. He.
  • Journal Title: Autophagy Volume: 12 Issue: 9 Pages: 1460-1471
  • DOI: 10.1080/15548627.2016.1187367
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] The novel JNK inhibitor AS602801 inhibits cancer stem cells in vitro and in vivo. (2016)
  • Author(s): Okada M, Kuramoto K, Takeda H, Watarai H, Sakaki H, Seino S, Seino M, Suzuki S, Kitanaka C.
  • Journal Title: Oncotarget Volume: 19 Issue: 19 Pages: 27021-27032
  • DOI: 10.18632/oncotarget.8395
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Time-staggered inhibition of JNK effectively sensitizes chemoresistant ovarian cancer cells to cisplatin and paclitaxel (2016)
  • Author(s): Seino M, Okada M, Sakaki H, Takeda H, Watarai H, Suzuki S, Seino S, Kuramoto K, Ohta T, Nagase S, Kurachi H, Kitanaka C
  • Journal Title: Oncology Reports Volume: 35 Issue: 1 Pages: 593-601
  • DOI: 10.3892/or.2015.4377
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Heart lipid droplets and lipid droplet-binding proteins: Biochemistry, physiology, and pathology. (2016)
  • Author(s): Osumi, T., Kuramoto, K.
  • Journal Title: Experimental Cell Research Volume: 340 Issue: 2 Pages: 198-204
  • DOI: 10.1016/j.yexcr.2015.10.031
  • Peer Reviewed / Acknowledgement Compliant