• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Elucidation of mechanism of oxidative stress resistance via metabolic reprogramming of hexosamine biosynthetic pathway in cancer stem cells

Research Project

Project/Area Number 17K15453
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Biological pharmacy
Research InstitutionKyoto Sangyo University

Principal Investigator

IZUMIKAWA Tomomi  京都産業大学, 総合生命科学部, 研究助教 (30780811)

Research Collaborator ITANO Naoki  
KOBAYASHI Takashi  
NISHIGAKI Daiki  
Project Period (FY) 2017-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsがん幹細胞 / ヒアルロン酸 / 酸化ストレス耐性 / 抗がん剤耐性 / 癌 / 糖鎖 / 薬学 / 酵素 / 発生・分化
Outline of Final Research Achievements

Cancer stem cells (CSCs) have the capability of self-renewal and giving rise to malignant progeny that drive cancer progression. CSCs are also thought to be responsible for cancer recurrence due to their resistance to oxidative stress. Thus, elucidating molecular mechanisms that govern CSCs can greatly contribute to designing new strategies for targeting cancer progression and recurrence. We recently demonstrated that hyaluronan (HA) production induced the CSC-like properties and metabolic reprogramming by accelerating the glycolysis and hexosamine biosynthetic pathway (HBP), which is a glucose metabolic pathway that branches off from the main glycolytic pathway. Here, we demonstrated that increased HA production in cancer cells induces resistance to oxidative stress, upregulation of reduced glutathione ratio and metabolic reprogramming by accelerating pentose phosphate pathway and glutaminolysis.

Academic Significance and Societal Importance of the Research Achievements

本研究では、ヒアルロン酸の過剰産生を介したがん幹細胞誘導機構の解明を通じてがん根治的治療の研究基盤の形成を目的に研究を行った。その結果、ヒアルロン酸高産生乳がん細胞において、細胞内のヒアルロン酸の合成基質経路であるヘキソサミン合成経路の異常亢進が引き金となり、他の代謝経路を促進することを明らかにした。さらに、これらの代謝経路が亢進することにより、酸化ストレス耐性に関わるシグナルが誘導され、がん幹細胞様細胞の出現を促していることが示された。これらの結果より、新規のがん幹細胞誘導機構が示され、その機構を標的とした治療法の開発への応用が期待される。

Report

(1 results)
  • 2018 Final Research Report ( PDF )

URL: 

Published: 2017-04-28   Modified: 2025-01-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi