Elucidation of an oncogenic mechanism that induced by the prion-like proteins

• Project/Area Number: 18K07199
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Health Sciences University of Hokkaido (2020); Yamaguchi University (2018-2019)
• Principal Investigator: KITAGAWA Takao 北海道医療大学, 先端研究推進センター, 助教 (20614928)
• Co-Investigator(Kenkyū-buntansha): 荒木 令江 熊本大学, 大学院生命科学研究部(医), 准教授 (80253722)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: ユーイング肉腫 / インタラクトーム解析 / BioID / 質量分析 / ewing sarcoma / EWS-FLI1

Outline of Final Research Achievements

Ewing's sarcoma is a tumor that arises from bone and soft tissue in young children. We performed an identification of the proximal proteins of the chimeric oncogenic transcription factors, using the BioID method, which is used active biotin ligase from E. coli for a biotinylation of the proximal proteins. Finally, we were able to identify 167 proteins that are commonly present in the three chimeric cancer transcription factors. Among these, a large number of proteins were identified, including chromatin remodeling complexes, transcription factors, RNA-binding proteins, and super enhancer-forming molecules. We were able to reproduce eight of the candidate proteins using antibodies. We are currently conducting phenotypic analysis of the candidate proteins by suppressing their expression.

Academic Significance and Societal Importance of the Research Achievements

ユーイング肉腫は小児で起こる癌であり、癌遺伝子に対するタンパク質の相互作用ネットワークを明らかにすることは、がん化の分子メカニズムを解明するだけでなく、抗がん剤のターゲット候補の同定も期待できる。本研究課題では、ユーイング肉腫細胞で新規の相互作用タンパク質同定法によって新しいタンパク質複合体の同定をすることができた。しかし、分子メカニズムの解明には至っていないため、今後同定したタンパク質の解析を行う予定である。

Research Products

• [Int'l Joint Research] Malta university(マルタ)
• [Journal Article] Up‐regulation of the pentose phosphate pathway and HIF‐1α expression during neural progenitor cell induction following glutamate treatment in rat ex vivo retina (2019)
  • Author(s): Tokuda Kazuhiro、Baron Byron、Yamashiro Chiemi、Kuramitsu Yasuhiro、Kitagawa Takao、Kobayashi Masaaki、Sonoda Koh‐Hei、Kimura Kazuhiro
  • Journal Title: Cell Biology International Volume: 44 Issue: 1 Pages: 137-144
  • DOI: 10.1002/cbin.11212
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] CUB domain-containing protein 1 (CDCP1) was down-regulated by active hexose-correlated compound in human pancreatic cancer cells. (2018)
  • Author(s): Kuhara K, Tokuda K, Kitagawa T, Baron B, Tokunaga M, Harada K, Terasaki M, Uehara O, Ohta T, Takai R, Hamada J, Kobayashi M, Shimo T, Nagayasu H, Kuramitsu Y.
  • Journal Title: Anticancer Research Volume: 38 Issue: 11 Pages: 6107-6111
  • DOI: 10.21873/anticanres.12961
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Enzyme treated asparagus extract down-regulates heat shock protein 27 of pancreatic cancer cells. (2018)
  • Author(s): Shimada T, Nanimoto Y, Baron B, Kitagawa T, Tokuda K, Kuramitsu Y.
  • Journal Title: In Vivo Volume: 32 Issue: 4 Pages: 759-763
  • DOI: 10.21873/invivo.11305
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Optimization of fixative solution for retinal morphology: a comparison with Davidson’s fixative and other fixation solutions (2018)
  • Author(s): Tokuda Kazuhiro、Baron Byron、Kuramitsu Yasuhiro、Kitagawa Takao、Tokuda Nobuko、Morishige Naoyuki、Kobayashi Masaaki、Kimura Kazuhiro、Nakamura Kazuyuki、Sonoda Koh-Hei
  • Journal Title: Japanese Journal of Ophthalmology Volume: 62 Issue: 4 Pages: 481-490
  • DOI: 10.1007/s10384-018-0592-7
  • Peer Reviewed / Open Access / Int'l Joint Research