Role of Thymidine Catabolism in Human Cancer Cells

• Project/Area Number: 26870576
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pathological medical chemistry; Tumor biology
• Research Institution: Keio University
• Principal Investigator: Tabata Sho 慶應義塾大学, 政策・メディア研究科(藤沢), 特任助教 (30708342)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: thymidine catabolism / thymidine phosphorylase / 解糖系 / thymidine

Outline of Final Research Achievements

Thymidine phosphorylase (TP), a rate-limiting enzyme in thymidine catabolism, plays a pivotal role in tumor progression; however, the mechanisms underlying this role are not fully understood. Here, we found that TP-mediated thymidine catabolism could supply the carbon source in the glycolytic pathway and thus contribute to cell survival under conditions of nutrient deprivation. In TP-expressing cells, thymidine was converted to metabolites including glucose 6-phosphate, lactate and 5-phosphoribosyl 1α-diphosphate via the glycolytic pathway both in vitro and in vivo. These thymidine-derived metabolites were required for the survival of cells in low glucose conditions. Furthermore, energy metabolism activated by thymidine catabolism was observed in human gastric cancer. These findings demonstrate that thymidine can serve as a novel energy source in human cancer cells.

Research Products

• [Journal Article] Fibrocyte-like cells mediate acquired resistance to anti-angiogenic therapy with bevacizumab (2015)
  • Author(s): Mitsuhashi A, Goto H, Saijo A, Trung VT, Aono Y, Ogino H, Kuramoto T, Tabata S, Uehara H, Izumi K, Yoshida M, Kobayashi H, Takahashi H, Gotoh M, Kakiuchi S, Hanibuchi M, Yano S, Yokomisa H, Sakiyama S, Nishioka Y
  • Journal Title: Nature Communications Volume: 6 Issue: 1 Pages: 8792-8792
  • DOI: 10.1038/ncomms9792
  • NAID: 120006999406
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Metabolomic alterations in human cancer cells by vitamin C-induced oxidative stress. (2015)
  • Author(s): Uetaki M, Tabata S, Nakasuka F, Soga T, Tomita M.
  • Journal Title: Sci Rep. Volume: 5 Issue: 1 Pages: 13896-13896
  • DOI: 10.1038/srep13896
  • Peer Reviewed / Open Access
• [Journal Article] Ribonucleotide reductase is an effective target to overcome gemcitabine resistance in gemcitabine-resistant pancreatic cancer cells with dual resistant factors (2015)
  • Author(s): Minami K, Shinsato Y, Yamamoto M, Takahashi H, Zhang S, Nishizawa Y, Tabata S, Ikeda R, Kawahara K, Tsujikawa K, Chijiiwa K, Yamada K, Akiyama S, Torras S, Pastor-Anglada M, Furukawa T, Yasuo T.
  • Journal Title: J Pharmacol Sci Volume: 127 Issue: 3 Pages: 319-325
  • DOI: 10.1016/j.jphs.2015.01.006
  • Peer Reviewed / Open Access
• [Journal Article] Systems Biology Strategy Reveals PKC-delta is Key for Sensitizing TRAIL-Resistant Human Fibrosarcoma (2015)
  • Author(s): Hayashi K, Tabata S, Piras V, Tomita M & Selvarajoo K
  • Journal Title: Frontiers in Immunology Volume: 5 Pages: 659-659
  • DOI: 10.3389/fimmu.2014.00659
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Thymidine phosphorylase activates NFκB and stimulates the expression of angiogenic and metastatic factors in human cancer cells. (2014)
  • Author(s): Tabata S, Ikeda R, Yamamoto M, Shimaoka S, Mukaida N, Takeda Y, Yamada K, Soga T, Furukawa T, Akiyama S.
  • Journal Title: Oncotarget. Volume: 15 Pages: 10473-10485
  • Peer Reviewed / Open Access
• [Journal Article] Expression of ABCB6 is related to resistance to 5-FU, SN-38 and vincristine. (2014)
  • Author(s): Minami K, Kamijo Y, Nishizawa Y, Tabata S, Horikuchi F, Yamamoto M, Kawahara K, Shinsato Y, Tachiwada T, Chen ZS, Tsujikawa K, Nakagawa M, Seki N, Akiyama S, Arima K, Takeda Y, Furukawa T.
  • Journal Title: Anticancer Res. Volume: 34 Pages: 4767-4773
  • Peer Reviewed
• [Presentation] Novel Thymidine Catabolism for ROS Generation and Survival in Human Cancer Cells (2016)
  • Author(s): Sho Tabata, Masatatsu Yamamoto, Hisatsugu Goto, Yasuhiko Nishioka, Masaru Tomita, Tomoyoshi Soga, Tatsuhiko Furukawa and Shin-ichi Akiyama.
  • Organizer: Tenth AACR-JCA Joint Conference on Breakthroughs in Cancer
  • Place of Presentation: Maui, Hawaii, USA
  • Year and Date: 2016-02-16
  • Int'l Joint Research